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2014

Dairy products and risk of hepatocellular carcinoma: The European Prospective Investigation into Cancer and Nutrition

Duarte-Salles T., Fedirko V., Stepien M., Trichopoulou A., Bamia C., Lagiou P., Lukanova A., Trepo E., Overvad K., Tjonneland A., Halkjaer J., Boutron-Ruault M.C., Racine A., Cadeau C., Kuhn T., Aleksandrova K., Trichopoulos D., Tsiotas K., Boffetta P., Palli D., Pala V., Tumino R., Sacerdote C., Panico S., Bueno-de-Mesquita H.B., Dik V.K., Peeters P.H., Weiderpass E., Torhild Gram I, Hjartaker A., Ramon Quiros J., Fonseca-Nunes A., Molina-Montes E., Dorronsoro M., Navarro Sanchez C., Barricarte A., Lindkvist B., Sonestedt E., Johansson I., Wennberg M., Khaw K.T., Wareham N., Travis R.C., Romieu I., Riboli E., Jenab M.

Int J Cancer; 2014; 135(7): 1662-1672

Abstract as provided by PubMed

Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (Ncases = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (Ncases = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; ptrend = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; ptrend = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; ptrend = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration

Normalization to specific gravity prior to analysis improves information recovery from high resolution mass spectrometry metabolomic profiles of human urine

Edmands W.M., Ferrari P., Scalbert A.

Anal Chem; 2014; 86(21): 10925-10931

Abstract as provided by PubMed

Extraction of meaningful biological information from urinary metabolomic profiles obtained by liquid-chromatography coupled to mass spectrometry (MS) necessitates the control of unwanted sources of variability associated with large differences in urine sample concentrations. Different methods of normalization either before analysis (preacquisition normalization) through dilution of urine samples to the lowest specific gravity measured by refractometry, or after analysis (postacquisition normalization) to urine volume, specific gravity and median fold change are compared for their capacity to recover lead metabolites for a potential future use as dietary biomarkers. Twenty-four urine samples of 19 subjects from the European Prospective Investigation into Cancer and nutrition (EPIC) cohort were selected based on their high and low/nonconsumption of six polyphenol-rich foods as assessed with a 24 h dietary recall. MS features selected on the basis of minimum discriminant selection criteria were related to each dietary item by means of orthogonal partial least-squares discriminant analysis models. Normalization methods ranked in the following decreasing order when comparing the number of total discriminant MS features recovered to that obtained in the absence of normalization: preacquisition normalization to specific gravity (4.2-fold), postacquisition normalization to specific gravity (2.3-fold), postacquisition median fold change normalization (1.8-fold increase), postacquisition normalization to urinary volume (0.79-fold). A preventative preacquisition normalization based on urine specific gravity was found to be superior to all curative postacquisition normalization methods tested for discovery of MS features discriminant of dietary intake in these urinary metabolomic datasets

Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study

Emaus M.J., Van Gils C.H., Bakker M.F., Bisschop C.N., Monninkhof E.M., Bueno-de-Mesquita H.B., Travier N., Berentzen T.L., Overvad K., Tjonneland A., Romieu I., Rinaldi S., Chajes V., Gunter M.J., Clavel-Chapelon F., Fagherazzi G., Mesrine S., Chang-Claude J., Kaaks R., Boeing H., Aleksandrova K., Trichopoulou A., Naska A., Orfanos P., Palli D., Agnoli C., Tumino R., Vineis P., Mattiello A., Braaten T., Borch K.B., Lund E., Menendez V., Sanchez M.J., Navarro C., Barricarte A., Amiano P., Sund M., Andersson A., Borgquist S., Olsson A., Khaw K.T., Wareham N., Travis R.C., Riboli E., Peeters P.H., May A.M.

Int J Cancer; 2014; 135(12): 2887-2899

Abstract as provided by PubMed

Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3 : 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3 : 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood

Genetic association of gastric cancer with miRNA clusters including the cancer-related genes MIR29, MIR25, MIR93 and MIR106: Results from the EPIC-EURGAST study

Espinosa-Parrilla Y., Munoz X., Bonet C., Garcia N., Vencesla A., Yiannakouris N., Naccarati A., Sieri S., Panico S., Huerta J.M., Barricarte A., Menendez V., Sanchez-Cantalejo E., Dorronsoro M., Brennan P., Duarte-Salles T., Bueno-de-Mesquita B.As, Weiderpass E., Lund E., Clavel-Chapelon F., Boutron-Ruault M.C., Racine A., Numans M.E., Tumino R., Canzian F., Campa D., Sund M., Johansson M., Ohlsson B., Lindkvist B., Overvad K., Tjonneland A., Palli D., Travis R.C., Khaw K.T., Wareham N., Boeing H., Nesi G., Riboli E., Gonzalez C.A., Sala N.

Int J Cancer; 2014; 135(9): 2065-2076

Abstract as provided by PubMed

MicroRNAs (miRNAs) are post-transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single-nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log-additive model. Furthermore, several of these miRNAs passed the gene-based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR-29a/miR-29b-1 cluster were associated with diffuse subtype (minimum p-value = 1.7 x 10(-4) ; odds ratio, OR = 1.72; 95% confidence interval, CI = 1.30-2.28), two tagSNPs of the miR-25/miR-93/miR-106b cluster were associated with cardia GC (minimum p-value = 5.38 x 10(-3) ; OR = 0.56, 95% CI = 0.37-0.86) and one tagSNP of the miR-363/miR-92a-2/miR-19b-2/miR-20b/miR-18b/miR-106a cluster was associated with noncardia GC (minimum p-value = 5.40 x 10(-3) ; OR = 1.41, 95% CI = 1.12-1.78). Some functionally validated target genes of these miRNAs are implicated in cancer-related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis

Pre-diagnostic anthropometry and survival after colorectal cancer diagnosis in Western European populations

Fedirko V., Romieu I., Aleksandrova K., Pischon T., Trichopoulos D., Peeters P.H., Romaguera-Bosch D., Bueno-de-Mesquita H.B., Dahm C.C., Overvad K., Chirlaque M.D., Johansen C., Bidstrup P.E., Dalton S.O., Gunter M.J., Wark P.A., Norat T., Halkjaer J., Tjonneland A., Dik V.K., Siersema P.D., Boutron-Ruault M.C., Dossus L., Bastide N., Kuhn T., Kaaks R., Boeing H., Trichopoulou A., Klinaki E., Katsoulis M., Pala V., Panico S., Tumino R., Palli D., Vineis P., Weiderpass E., Skeie G., Gonzalez C.A., Sanchez M.J., Barricarte A., Amiano P., Quiros J.R., Manjer J., Jirstrom K., Ljuslinder I., Palmqvist R., Khaw K.T., Wareham N., Bradbury K.E., Stepien M., Duarte-Salles T., Riboli E., Jenab M.

Int J Cancer; 2014; 135(8): 1949-1960

Abstract as provided by PubMed

General and abdominal adiposity are associated with a high risk of developing colorectal cancer (CRC), but the role of these exposures on cancer survival has been less studied. The association between pre-diagnostic anthropometric characteristics and CRC-specific and all-cause death was examined among 3,924 men and women diagnosed with CRC between 1992 and 2009 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Over a mean follow-up period of 49 months, 1,309 deaths occurred of which 1,043 (79.7%) were due to CRC. In multivariable analysis, pre-diagnostic BMI >/=30 kg/m(2) was associated with a high risk for CRC-specific (HR = 1.26, 95% CI = 1.04-1.52) and all-cause (HR = 1.32, 95% CI = 1.12-1.56) death relative to BMI <25 kg/m(2) . Every 5 kg/m(2) increase in BMI was associated with a high risk for CRC-specific (HR = 1.10, 95% CI = 1.02-1.19) and all-cause death (HR = 1.12, 95% CI = 1.05-1.20); and every 10 cm increase in waist circumference was associated with a high risk for CRC-specific (HR = 1.09, 95% CI = 1.02-1.16) and all-cause death (HR = 1.11, 95% CI = 1.05-1.18). Similar associations were observed for waist-to-hip and waist-to-height ratios. Height was not associated with CRC-specific or all-cause death. Associations tended to be stronger among men than in women. Possible interactions by age at diagnosis, cancer stage, tumour location, and hormone replacement therapy use among postmenopausal women were noted. Pre-diagnostic general and abdominal adiposity are associated with lower survival after CRC diagnosis

Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case-control study

Fedirko V., Duarte-Salles T., Bamia C., Trichopoulou A., Aleksandrova K., Trichopoulos D., Trepo E., Tjonneland A., Olsen A., Overvad K., Boutron-Ruault M.C., Clavel-Chapelon F., Kvaskoff M., Kuhn T., Lukanova A., Boeing H., Buijsse B., Klinaki E., Tsimakidi C., Naccarati A., Tagliabue G., Panico S., Tumino R., Palli D., Bueno-de-Mesquita H.B., Siersema P.D., Peters P.H., Lund E., Brustad M., Olsen K.S., Weiderpass E., Zamora-Ros R., Sanchez M.J., Ardanaz E., Amiano P., Navarro C., Quiros J.R., Werner M., Sund M., Lindkvist B., Malm J., Travis R.C., Khaw K.T., Stepien M., Scalbert A., Romieu I., Lagiou P., Riboli E., Jenab M.

Hepatology; 2014; 60(4): 1222-1230

Abstract as provided by PubMed

The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n = 138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR = 0.51, 95% confidence interval [CI], 0.26 to 0.99; Ptrend = 0.04; per 10 nmol/L increase: IRR = 0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. CONCLUSION: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. (Hepatology 2014;60:1222-1230)

Lifetime alcohol use and overall and cause-specific mortality in the European Prospective Investigation into Cancer and nutrition (EPIC) study

Ferrari P., Licaj I., Muller D.C., Kragh Andersen P., Johansson M., Boeing H., Weiderpass E., Dossus L., Dartois L., Fagherazzi G., Bradbury K.E., Khaw K.T., Wareham N., Duell E.J., Barricarte A., Molina-Montes E., Sanchez C.N., Arriola L., Wallstrom P., Tjonneland A., Olsen A., Trichopoulou A., Benetou V., Trichopoulos D., Tumino R., Agnoli C., Sacerdote C., Palli D., Li K., Kaaks R., Peeters P., Beulens J.W., Nunes L., Gunter M., Norat T., Overvad K., Brennan P., Riboli E., Romieu I.

BMJ Open; 2014; 4(7): e005245

Abstract as provided by PubMed

OBJECTIVES: To investigate the role of factors that modulate the association between alcohol and mortality, and to provide estimates of absolute risk of death. DESIGN: The European Prospective Investigation into Cancer and nutrition (EPIC). SETTING: 23 centres in 10 countries. PARTICIPANTS: 380 395 men and women, free of cancer, diabetes, heart attack or stroke at enrolment, followed up for 12.6 years on average. MAIN OUTCOME MEASURES: 20 453 fatal events, of which 2053 alcohol-related cancers (ARC, including cancers of upper aerodigestive tract, liver, colorectal and female breast), 4187 cardiovascular diseases/coronary heart disease (CVD/CHD), 856 violent deaths and injuries. Lifetime alcohol use was assessed at recruitment. RESULTS: HRs comparing extreme drinkers (>/=30 g/day in women and >/=60 g/day in men) to moderate drinkers (0.1-4.9 g/day) were 1.27 (95% CI 1.13 to 1.43) in women and 1.53 (1.39 to 1.68) in men. Strong associations were observed for ARC mortality, in men particularly, and for violent deaths and injuries, in men only. No associations were observed for CVD/CHD mortality among drinkers, whereby HRs were higher in never compared to moderate drinkers. Overall mortality seemed to be more strongly related to beer than wine use, particularly in men. The 10-year risks of overall death for women aged 60 years, drinking more than 30 g/day was 5% and 7%, for never and current smokers, respectively. Corresponding figures in men consuming more than 60 g/day were 11% and 18%, in never and current smokers, respectively. In competing risks analyses, mortality due to CVD/CHD was more pronounced than ARC in men, while CVD/CHD and ARC mortality were of similar magnitude in women. CONCLUSIONS: In this large European cohort, alcohol use was positively associated with overall mortality, ARC and violent death and injuries, but marginally to CVD/CHD. Absolute risks of death observed in EPIC suggest that alcohol is an important determinant of total mortality

Adherence to predefined dietary patterns and incident type 2 diabetes in European populations: EPIC-InterAct Study

InterAct Consortium, Kroeger J., Slimani N., et al.

Diabetologia; 2014; 57(2): 321-333

Abstract as provided by PubMed

AIMS/HYPOTHESIS: Few studies have investigated the relationship between predefined dietary patterns and type 2 diabetes incidence; little is known about the generalisability of these associations. We aimed to assess the association between predefined dietary patterns and type 2 diabetes risk in European populations. METHODS: From among a case-cohort of 12,403 incident diabetes cases and 16,154 subcohort members nested within the prospective European Prospective Investigation into Cancer and Nutrition study, we used data on 9,682 cases and 12,595 subcohort participants from seven countries. Habitual dietary intake was assessed at baseline with country-specific dietary questionnaires. Two diet-quality scores (alternative Healthy Eating Index [aHEI], Dietary Approaches to Stop Hypertension [DASH] score) and three reduced rank regression (RRR)-derived dietary-pattern scores were constructed. Country-specific HRs were calculated and combined using a random-effects meta-analysis. RESULTS: After multivariable adjustment, including body size, the aHEI and DASH scores were not significantly associated with diabetes, although for the aHEI there was a tendency towards an inverse association in countries with higher mean age. We observed inverse associations of the three RRR-derived dietary-pattern scores with diabetes: HRs (95% CIs) for a 1-SD difference were 0.91 (0.86, 0.96), 0.92 (0.84, 1.01) and 0.87 (0.82, 0.92). Random-effects meta-analyses revealed heterogeneity between countries that was explainable by differences in the age of participants or the distribution of dietary intake. CONCLUSIONS/INTERPRETATION: Adherence to specific RRR-derived dietary patterns, commonly characterised by high intake of fruits or vegetables and low intake of processed meat, sugar-sweetened beverages and refined grains, may lower type 2 diabetes risk

Circulating biomarkers of one-carbon metabolism in relation to renal cell carcinoma incidence and survival

Johansson M., Fanidi A., Muller D.C., Bassett J.K., Midttun O., Vollset S.E., Travis R.C., Palli D., Mattiello A., Sieri S., Trichopoulou A., Lagiou P., Trichopoulos D., Ljungberg B., Hallmans G., Weiderpass E., Skeie G., Gonzalez C.A., Dorronsoro M., Peeters P.H., Bueno-de-Mesquita H.B., Ros M.M., Boutron Ruault M.C., Fagherazzi G., Clavel F., Sanchez M.J., Gurrea A.B., Navarro C., Quiros J.R., Overvad K., Tjonneland A., Aleksandrova K., Vineis P., Gunter M.J., Kaaks R., Giles G., Relton C., Riboli E., Boeing H., Ueland P.M., Severi G., Brennan P.

J Natl Cancer Inst; 2014; 106(12): pii: dju327

Abstract as provided by PubMed

BACKGROUND: The etiology of renal cell carcinoma (RCC) is only partially understood, but a metabolic component appears likely. We investigated biomarkers of one-carbon metabolism and RCC onset and survival. METHODS: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 385747 participants with blood samples between 1992 and 2000, and this analysis included 556 RCC case-control pairs. A subsequent replication study included 144 case-control pairs nested within the Melbourne Collaborative Cohort Study (MCCS). Plasma concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine and homocysteine were measured in prediagnostic samples and evaluated with respect to RCC risk using conditional and unconditional logistic regression models, and to all-cause mortality in RCC cases using Cox regression models. All statistical tests were two-sided. RESULTS: EPIC participants with higher plasma concentrations of vitamin B6 had lower risk of RCC, the odds ratio comparing the 4(th) and 1(st) quartiles (OR4vs1) being 0.40 95% confidence interval [CI] = 0.28 to 0.57, P trend < .001. We found similar results after adjusting for potential confounders (adjusted P trend < .001). In survival analysis, the hazard ratio for all-cause mortality in RCC cases when comparing the 4(th) and 1(st) quartiles (HR4vs1) of vitamin B6 was 0.57 (95% CI = 0.37 to 0.87, P trend < .001). Subsequent replication of these associations within the MCCS yielded very similar results for both RCC risk (OR4vs1 = 0.47, 95% CI = 0.23 to 0.99, P trend = .07) and all-cause mortality (HR4vs1 = 0.56, 95% CI = 0.27 to 1.17, P trend = .02). No association was evident for the other measured biomarkers. CONCLUSION: Study participants with higher circulating concentrations of vitamin B6 had lower risk of RCC and improved survival following diagnosis in two independent cohorts

Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status-Results from the EPIC cohort

Kaaks R., Tikk K., Sookthai D., Schock H., Johnson T., Tjonneland A., Olsen A., Overvad K., Clavel-Chapelon F., Dossus L., Baglietto L., Rinaldi S., Chajes V., Romieu I., Boeing H., Schutze M., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Sieri S., Tumino R., Ricceri F., Mattiello A., Buckland G., Ramon Quiros J., Sanchez M.J., Amiano P., Chirlaque M.D., Barricarte A., Bas Bueno-de-Mesquita H., Van Gils C.H., Peeters P.H., Andersson A., Sund M., Weiderpass E., Khaw K.T., Wareham N., Key T.J., Travis R.C., Merritt M.A., Gunter M.J., Riboli E., Lukanova A.

Int J Cancer; 2014; 134(8): 1947-1957

Abstract as provided by PubMed

Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1 = 1.56 (95% CI 1.15-2.13), ptrend = 0.02 for testosterone and ORQ4-Q1 = 1.33 (95% CI 0.99-1.79), ptrend = 0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1 = 1.32 (95% CI 0.87-2.01), ptrend = 0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1 = 0.94 (95% CI 0.60-1.47), ptrend = 0.34, phet = 0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen

Risk factors for cancers of unknown primary site: Results from the prospective EPIC cohort

Kaaks R., Sookthai D., Hemminki K., Kramer A., Boeing H., Wirfalt E., Weiderpass E., Overvad K., Tjonneland A., Olsen A., Peeters P.H., Bueno-de-Mesquita H.B., Panico S., Pala V., Vineis P., Quiros J.R., Ardanaz E., Sanchez M.J., Chirlaque M.D., Larranaga N., Brennan P., Trichopoulos D., Trichopoulou A., Lagiou P., Hallmans G., Khaw K.T., Key T.J., Riboli E., Canzian F.

Int J Cancer; 2014; 135(10): 2475-2481

Abstract as provided by PubMed

Cancer of unknown primary site (CUP) may be called an "orphan" disease, as it is diagnosed when metastases are detected while the primary tumor typically remains undetected, and because little research has been done on its primary causes. So far, few epidemiological studies, if any, have addressed possible risk factors for CUP. We analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (N = 476,940). During prospective follow-up, a total of 651 cases of incident cases of CUP were detected (ICD-O-2 code C809). Proportional hazards models were conducted to examine the associations of lifetime history of smoking habits, alcohol consumption, levels of education and anthropometric indices of adiposity with risk of being diagnosed with CUP. Risk of being diagnosed with CUP was strongly related to smoking, with a relative risk of 3.66 [95% C.I., 2.24-5.97] for current, heavy smokers (26+ cigarettes/day) compared to never smokers (adjusted for alcohol consumption, body mass index, waist circumference and level of education) and a relative risk of 5.12 [3.09-8.47] for cases with CUP who died within 12 months. For alcohol consumption and level of education, weaker associations were observed but attenuated and no longer statistically significant after adjusting for smoking and indices of obesity. Finally, risk of CUP was increased by approximately 30 per cent for subjects in the highest versus lowest quartiles of waist circumference. Our analyses provide further documentation, in addition to autopsy studies, that a substantial proportion of cancers of unknown primary site may have their origin in smoking-related tumors, in particular

Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and incidence of colorectal cancer

Kyro C., Olsen A., Landberg R., Skeie G., Loft S., Aman P., Leenders M., Dik V.K., Siersema P.D., Pischon T., Christensen J., Overvad K., Boutron-Ruault M.C., Fagherazzi G., Cottet V., Kuhn T., Chang-Claude J., Boeing H., Trichopoulou A., Bamia C., Trichopoulos D., Palli D., Krogh V., Tumino R., Vineis P., Panico S., Peeters P.H., Weiderpass E., Bakken T., Asli L.A., Arguelles M., Jakszyn P., Sanchez M.J., Amiano P., Huerta J.M., Barricarte A., Ljuslinder I., Palmqvist R., Khaw K.T., Wareham N., Key T.J., Travis R.C., Ferrari P., Freisling H., Jenab M., Gunter M.J., Murphy N., Riboli E., Tjonneland A., Bueno-de-Mesquita H.B.

J Natl Cancer Inst; 2014; 106(1): djt352

Abstract as provided by PubMed

BACKGROUND: Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations. METHODS: The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored. RESULTS: High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). CONCLUSIONS: High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer

Plasma alkylresorcinol concentrations, biomarkers of whole-grain wheat and rye intake, in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Kyro C., Olsen A., Bueno-de-Mesquita H.B., Skeie G., Loft S., Aman P., Leenders M., Dik V.K., Siersema P.D., Pischon T., Christensen J., Overvad K., Boutron-Ruault M.C., Fagherazzi G., Cottet V., Kuhn T., Chang-Claude J., Boeing H., Trichopoulou A., Naska A., Oikonomidou D., Masala G., Pala V., Tumino R., Vineis P., Mattiello A., Peeters P.H., Bakken T., Weiderpass E., Asli L.A., Sanchez S., Jakszyn P., Sanchez M.J., Amiano P., Huerta J.M., Barricarte A., Ljuslinder I., Palmqvist R., Khaw K.T., Wareham N., Key T.J., Travis R.C., Slimani N., Freisling H., Ferrari P., Gunter M.J., Murphy N., Riboli E., Tjonneland A., Landberg R.

Br J Nutr; 2014; 111(10): 1881-1890

Abstract as provided by PubMed

Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41 nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23 nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye

Fruit and vegetable intake and cause-specific mortality in the EPIC study

Leenders M., Boshuizen H.C., Ferrari P., Siersema P.D., Overvad K., Tjonneland A., Olsen A., Boutron-Ruault M.C., Dossus L., Dartois L., Kaaks R., Li K., Boeing H., Bergmann M.M., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Krogh V., Panico S., Tumino R., Vineis P., Peeters P.H., Weiderpass E., Engeset D., Braaten T., Redondo M.L., Agudo A., Sanchez M.J., Amiano P., Huerta J.M., Ardanaz E., Drake I., Sonestedt E., Johansson I., Winkvist A., Khaw K.T., Wareham N.J., Key T.J., Bradbury K.E., Johansson M., Licaj I., Gunter M.J., Murphy N., Riboli E., Bueno-de-Mesquita H.B.

Eur J Epidemiol; 2014; 29(9): 639-652

Abstract as provided by PubMed

Consumption of fruits and vegetables is associated with a lower overall mortality. The aim of this study was to identify causes of death through which this association is established. More than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition study were included, of which 25,682 were reported deceased after 13 years of follow-up. Information on lifestyle, diet and vital status was collected through questionnaires and population registries. Hazard ratios (HR) with 95 % confidence intervals (95 % CI) for death from specific causes were calculated from Cox regression models, adjusted for potential confounders. Participants reporting consumption of more than 569 g/day of fruits and vegetables had lower risks of death from diseases of the circulatory (HR for upper fourth 0.85, 95 % CI 0.77-0.93), respiratory (HR for upper fourth 0.73, 95 % CI 0.59-0.91) and digestive system (HR for upper fourth 0.60, 95 % CI 0.46-0.79) when compared with participants consuming less than 249 g/day. In contrast, a positive association with death from diseases of the nervous system was observed. Inverse associations were generally observed for vegetable, but not for fruit consumption. Associations were more pronounced for raw vegetable consumption, when compared with cooked vegetable consumption. Raw vegetable consumption was additionally inversely associated with death from neoplasms and mental and behavioral disorders. The lower risk of death associated with a higher consumption of fruits and vegetables may be derived from inverse associations with diseases of the circulatory, respiratory and digestive system, and may depend on the preparation of vegetables and lifestyle factors

Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

Leenders M., Leufkens A.M., Siersema P.D., van Duijnhoven F.J., Vrieling A., Hulshof P.J., Van Gils C.H., Overvad K., Roswall N., Kyro C., Boutron-Ruault M.C., Fagerhazzi G., Cadeau C., Kuhn T., Johnson T., Boeing H., Aleksandrova K., Trichopoulou A., Klinaki E., Androulidaki A., Palli D., Grioni S., Sacerdote C., Tumino R., Panico S., Bakker M.F., Skeie G., Weiderpass E., Jakszyn P., Barricarte A., Maria Huerta J., Molina-Montes E., Arguelles M., Johansson I., Ljuslinder I., Key T.J., Bradbury K.E., Khaw K.T., Wareham N.J., Ferrari P., Duarte-Salles T., Jenab M., Gunter M.J., Vergnaud A.C., Wark P.A., Bueno-de-Mesquita H.B.

Int J Cancer; 2014; 135(12): 2930-2939

Abstract as provided by PubMed

Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (alpha- and beta-carotene, canthaxanthin, beta-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (alpha-, beta- and gamma- and delta-tocopherol) and dietary consumption of beta-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary beta-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties

Dietary intake of acrylamide and esophageal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Lujan-Barroso L., Gonzalez C.A., Slimani N., Obon-Santacana M., Ferrari P., Freisling H., Overvad K., Clavel-Chapelon F., Boutron-Ruault M.C., Racine A., Katzke V., Kuhn T., Tjonneland A., Olsen A., Quiros J.R., Sanchez-Cantalejo E., Amiano P., Navarro C., Barricarte A., Khaw K.T., Wareham N., Travis R.C., Trichopoulou A., Bamia C., Benetou V., Saieva C., Grioni S., Tumino R., Vineis P., Mattiello A., Bueno-de-Mesquita H.B., Siersema P.D., Numans M.E., Peeters P.H., Ericson U., Wirfalt E., Sund M., Johansson M., Weiderpass E., Skeie G., Riboli E., Boeing H., Duell E.J.

Cancer Causes Control; 2014; 25(5): 639-646

Abstract as provided by PubMed

PURPOSE: The relation between dietary acrylamide intake and esophageal cancer (EC) risk, including esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), has not been consistent. We evaluated the association between dietary acrylamide intake and EAC, ESCC, and overall EC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Multivariate Cox proportional hazards models were used to estimate the HR and 95 % confidence interval (95 % CI). Since nonlinear relations were observed, HRs were displayed for quartiles of acrylamide intake in mug per day. RESULTS: After a mean follow-up of 11 years, 341 EC were identified, 142 of which were EAC, 176 ESCC, and 23 other histological types or not specified. An increase in EC risk was observed in the second and third quartiles (HRQ2vsQ1 1.75, 95 % CI 1.12-2.74; HRQ3vsQ1 1.66, 95 % CI 1.05-2.61), but not in the fourth quartile, and there was no evidence for a linear dose-response trend. HRs were similarly elevated but not statistically significant when ESCC and EAC were analyzed separately, due to the small number of cases observed. No associations were observed when quartiles were based on energy-adjusted acrylamide intake. CONCLUSIONS: In the EPIC cohort, an association between estimated dietary acrylamide intake and an increased risk of developing EC was observed in the middle quartiles but not in the highest quartile; however, results from other larger cohorts or consortia, and results from biomarker studies, might add to the evidence provided by this analysis, suggesting that acrylamide is not an important risk factor for EC

Prediagnostic plasma testosterone, sex hormone-binding globulin, IGF-I and hepatocellular carcinoma: etiological factors or risk markers?

Lukanova A., Becker S., Husing A., Schock H., Fedirko V., Trepo E., Trichopoulou A., Bamia C., Lagiou P., Benetou V., Trichopoulos D., Nothlings U., Tjonneland A., Overvad K., Dossus L., Teucher B., Boeing H., Aleksandrova K., Palli D., Pala V., Panico S., Tumino R., Ricceri F., Bueno-de-Mesquita H.B., Siersema P.D., Peeters P.H., Quiros J.R., Duell E.J., Molina-Montes E., Chirlaque M.D., Gurrea A.B., Dorronsoro M., Lindkvist B., Johansen D., Werner M., Sund M., Khaw K.T., Wareham N., Key T.J., Travis R.C., Rinaldi S., Romieu I., Gunter M.J., Riboli E., Jenab M., Kaaks R.

Int J Cancer; 2014; 134(1): 164-173

Abstract as provided by PubMed

Elevated prediagnostic testosterone and insulin-like growth factor I (IGF-I) concentrations have been proposed to increase risk of hepatocellular carcinoma (HCC). However, the metabolism of these hormones is altered as a consequence of liver damage and they may have clinical utility as HCC risk markers. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition cohort and included 125 incident HCC cases and 247 individually matched controls. Testosterone, sex hormone-binding globulin (SHBG) and IGF-I were analyzed by immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression. The area under the receiver operating curves (AUC) was calculated to assess HCC predictive ability of the tested models. After adjustments for epidemiological variables (body mass index, smoking, ethanol intake, hepatitis and diabetes) and liver damage (a score based on albumin, bilirubin, aspartate aminotransaminase, alanine aminotransaminase, gamma-glutamyltransferase and alkaline phosphatase concentrations), only SHBG remained significantly associated with risk [OR for top versus bottom tertile of 3.86 (1.32-11.3), p(trend) = 0.009]. As a single factor SHBG had an AUC of 0.81 (0.75-0.86). A small, but significant increase in AUC was observed when SHBG was added to a model including the liver damage score and epidemiological variables (from 0.89 to 0.91, p = 0.02) and a net reclassification of 0.47% (0.45-0.48). The observed associations of HCC with prediagnostic SHBG, free testosterone and IGF-I concentrations are in directions opposite to that expected under the etiological hypotheses. SHBG has a potential to be tested as prediagnostic risk marker for HCC

Dietary fat intake and risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition

Merritt M.A., Riboli E., Weiderpass E., Tsilidis K.K., Overvad K., Tjonneland A., Hansen L., Dossus L., Fagherazzi G., Baglietto L., Fortner R.T., Ose J., Steffen A., Boeing H., Trichopoulou A., Trichopoulos D., Lagiou P., Masala G., Sieri S., Mattiello A., Tumino R., Sacerdote C., Bueno-de-Mesquita H.B., Onland-Moret N.C., Peeters P.H., Hjartaker A., Gram I.T., Quiros J.R., Obon-Santacana M., Molina-Montes E., Huerta Castano J.M., Ardanaz E., Chamosa S., Sonestedt E., Idahl A., Lundin E., Khaw K.T., Wareham N., Travis R.C., Rinaldi S., Romieu I., Chajes V., Gunter M.J.

Cancer Epidemiol; 2014; 38(5): 528-537

Abstract as provided by PubMed

There are inconsistent and limited data available to assess the relationship between fat intake and risk of epithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes in relation to risk of EOC and its major histologic subtypes in the European Prospective Investigation into Cancer and Nutrition which includes incident invasive (n=1095) and borderline (n=96) EOC. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariate models, we observed no association with consumption of total fat, animal or plant fat, saturated fat, cholesterol, monounsaturated fat, or fatty fish and risk of invasive EOC. There was, however, an increased risk of invasive EOC in the highest category of intake (Quartile 4 vs. Quartile 1) of polyunsaturated fat (HR=1.22, 95% CI=1.02-1.48, Ptrend=0.02). We did not observe heterogeneity in the risk associations in comparisons of serous and endometrioid histologic subtypes. This study does not support an etiological role for total fat intake in relation to EOC risk; however, based on observations of a positive association between intake of polyunsaturated fat and invasive EOC risk in the current and previous studies, this fat subtype warrants further investigation to determine its potential role in EOC development

Nutrient Patterns and Their Food Sources in an International Study Setting: Report from the EPIC Study

Moskal A., Pisa P.T., Ferrari P., Byrnes G., Freisling H., Boutron-Ruault M.C., Cadeau C., Nailler L., Wendt A., Kuhn T., Boeing H., Buijsse B., Tjonneland A., Halkjaer J., Dahm C.C., Chiuve S.E., Quiros J.R., Buckland G., Molina-Montes E., Amiano P., Huerta Castano J.M., Gurrea A.B., Khaw K.T., Lentjes M.A., Key T.J., Romaguera D., Vergnaud A.C., Trichopoulou A., Bamia C., Orfanos P., Palli D., Pala V., Tumino R., Sacerdote C., de Magistris M.S., Bueno-de-Mesquita H.B., Ocke M.C., Beulens J.W., Ericson U., Drake I., Nilsson L.M., Winkvist A., Weiderpass E., Hjartaker A., Riboli E., Slimani N.

PLoS ONE; 2014; 9(6): e98647

Abstract as provided by PubMed

BACKGROUND: Compared to food patterns, nutrient patterns have been rarely used particularly at international level. We studied, in the context of a multi-center study with heterogeneous data, the methodological challenges regarding pattern analyses. METHODOLOGY/PRINCIPAL FINDINGS: We identified nutrient patterns from food frequency questionnaires (FFQ) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR) data to validate and describe the nutrient patterns and their related food sources. Associations between lifestyle factors and the nutrient patterns were also examined. Principal component analysis (PCA) was applied on 23 nutrients derived from country-specific FFQ combining data from all EPIC centers (N = 477,312). Harmonized 24-HDRs available for a representative sample of the EPIC populations (N = 34,436) provided accurate mean group estimates of nutrients and foods by quintiles of pattern scores, presented graphically. An overall PCA combining all data captured a good proportion of the variance explained in each EPIC center. Four nutrient patterns were identified explaining 67% of the total variance: Principle component (PC) 1 was characterized by a high contribution of nutrients from plant food sources and a low contribution of nutrients from animal food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized by calcium, proteins, riboflavin, and phosphorus. The nutrients with high loadings on a particular pattern as derived from country-specific FFQ also showed high deviations in their mean EPIC intakes by quintiles of pattern scores when estimated from 24-HDR. Center and energy intake explained most of the variability in pattern scores. CONCLUSION/SIGNIFICANCE: The use of 24-HDR enabled internal validation and facilitated the interpretation of the nutrient patterns derived from FFQs in term of food sources. These outcomes open research opportunities and perspectives of using nutrient patterns in future studies particularly at international level

Circulating 25-Hydroxyvitamin D3 in Relation to Renal Cell Carcinoma Incidence and Survival in the EPIC Cohort

Muller D.C., Fanidi A., Midttun O., Steffen A., Dossus L., Boutron-Ruault M.C., Severi G., Kuhn T., Katzke V., de la Torre R.A., Gonzalez C.A., Sanchez M.J., Dorronsoro M., Santiuste C., Barricarte A., Khaw K.T., Wareham N., Travis R.C., Trichopoulou A., Giotaki M., Trichopoulos D., Palli D., Krogh V., Tumino R., Vineis P., Panico S., Tjonneland A., Olsen A., Bueno-de-Mesquita H.B., Peeters P.H., Ljungberg B., Wennberg M., Weiderpass E., Murphy N., Riboli E., Ueland P.M., Boeing H., Brennan P., Johansson M.

Am J Epidemiol; 2014; 180(8): 810-820

Abstract as provided by PubMed

Normal renal function is essential for vitamin D metabolism, but it is unclear whether circulating vitamin D is associated with risk of renal cell carcinoma (RCC). We assessed whether 25-hydroxyvitamin D3 (25(OH)D3) was associated with risk of RCC and death after RCC diagnosis in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC recruited 385,747 participants with blood samples between 1992 and 2000. The current study included 560 RCC cases, 557 individually matched controls, and 553 additional controls. Circulating 25(OH)D3 was assessed by mass spectrometry. Conditional and unconditional logistic regression models were used to calculate odds ratios and 95% confidence intervals. Death after RCC diagnosis was assessed using Cox proportional hazards models and flexible parametric survival models. A doubling of 25(OH)D3 was associated with 28% lower odds of RCC after adjustment for season of and age at blood collection, sex, and country of recruitment (odds ratio = 0.72, 95% confidence interval: 0.60, 0.86; P = 0.0004). This estimate was attenuated somewhat after additional adjustment for smoking status at baseline, circulating cotinine, body mass index (weight (kg)/height (m)(2)), and alcohol intake (odds ratio = 0.82, 95% confidence interval: 0.68, 0.99; P = 0.038). There was also some indication that both low and high 25(OH)D3 levels were associated with higher risk of death from any cause among RCC cases

Prediagnostic immunoglobulin E levels and risk of chronic lymphocytic leukemia, other lymphomas and multiple myeloma-results of the European Prospective Investigation into Cancer and Nutrition

Nieters A., Luczynska A., Becker S., Becker N., Vermeulen R., Overvad K., Aleksandrova K., Boeing H., Lagiou P., Trichopoulos D., Trichopoulou A., Krogh V., Masala G., Panico S., Tumino R., Sacerdote C., Bueno-de-Mesquita B., Jeurnink S.M., Weiderpass E., Ardanaz E., Chirlaque M.D., Sanchez M.J., Sanchez S., Borgquist S., Butt S., Melin B., Spath F., Rinaldi S., Brennan P., Kelly R.S., Riboli E., Vineis P., Kaaks R.

Carcinogenesis; 2014; 35(12): 2716-2722

Abstract as provided by PubMed

Previous epidemiological studies suggest an inverse association between allergies, marked by elevated immunoglobulin (Ig) E levels, and non-Hodgkin lymphoma (NHL) risk. The evidence, however, is inconsistent and prospective data are sparse. We examined the association between prediagnostic total (low: <20; intermediate: 20-100; high >100 kU/l) and specific IgE (negative: <0.35; positive >/=0.35 kU/I) concentrations against inhalant antigens and lymphoma risk in a study nested within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 1021 incident cases and matched controls of NHL, multiple myeloma (MM) and Hodgkin lymphoma with a mean follow-up time of 7 years were investigated. Multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CI) were calculated by conditional logistic regression. Specific IgE was not associated with the risk of MM, B-cell NHL and B-cell NHL subtypes. In contrast, total IgE levels were inversely associated with the risk of MM [high level: OR = 0.40 (95% CI = 0.21-0.79)] and B-cell NHL [intermediate level: OR = 0.68 (95% CI = 0.53-0.88); high level: OR = 0.62 (95% CI = 0.44-0.86)], largely on the basis of a strong inverse association with chronic lymphocytic leukemia [CLL; intermediate level: OR = 0.49 (95% CI = 0.30-0.80); high level: OR = 0.13 (95% CI = 0.05-0.35)] risk. The inverse relationship for CLL remained significant for those diagnosed 5 years after baseline. The findings of this large prospective study demonstrated significantly lower prediagnostic total IgE levels among CLL and MM cases compared with matched controls. This corresponds to the clinical immunodeficiency state often observed in CLL patients prior to diagnosis. No support for an inverse association between prediagnostic levels of specific IgE and NHL risk was found

Plasma methionine, choline, betaine, and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Nitter M., Norgard B., de Vogel S., Eussen S.J., Meyer K., Ulvik A., Ueland P.M., Nygard O., Vollset S.E., Bjorge T., Tjonneland A., Hansen L., Boutron-Ruault M., Racine A., Cottet V., Kaaks R., Kuhn T., Trichopoulou A., Bamia C., Naska A., Grioni S., Palli D., Panico S., Tumino R., Vineis P., Bueno-de-Mesquita H.B., van Kranen H., Peeters P.H., Weiderpass E., Dorronsoro M., Jakszyn P., Sanchez M., Arguelles M., Huerta J.M., Barricarte A., Johansson M., Ljuslinder I., Khaw K., Wareham N., Freisling H., Duarte-Salles T., Stepien M., Gunter M.J., Riboli E.

Ann Oncol; 2014; 25(8): 1609-1615

Abstract as provided by PubMed

BACKGROUND: Disturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low. PATIENTS AND METHODS: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations. RESULTS: Overall, methionine (OR: 0.79, 95% CI: 0.63-0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60-0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66-1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50-1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43-0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk. CONCLUSIONS: Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC

Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Obon-Santacana M., Kaaks R., Slimani N., Lujan-Barroso L., Freisling H., Ferrari P., Dossus L., Chabbert-Buffet N., Baglietto L., Fortner R.T., Boeing H., Tjonneland A., Olsen A., Overvad K., Menendez V., Molina-Montes E., Larranaga N., Chirlaque M.D., Ardanaz E., Khaw K.T., Wareham N., Travis R.C., Lu Y., Merritt M.A., Trichopoulou A., Benetou V., Trichopoulos D., Saieva C., Sieri S., Tumino R., Sacerdote C., Galasso R., Bueno-de-Mesquita H.B., Wirfalt E., Ericson U., Idahl A., Ohlson N., Skeie G., Gram I.T., Weiderpass E., Onland-Moret N.C., Riboli E., Duell E.J.

Br J Cancer; 2014; 111(5): 987-997

Abstract as provided by PubMed

BACKGROUND: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. METHODS: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. RESULTS: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n=203). CONCLUSIONS: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers

Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women: a cross-sectional study within the EPIC cohort

Rinaldi S., Kaaks R., Friedenreich C.M., Key T.J., Travis R., Biessy C., Slimani N., Overvad K., Ostergaard J.N., Tjonneland A., Olsen A., Mesrine S., Fournier A., Dossus L., Lukanova A., Johnson T., Boeing H., Vigl M., Trichopoulou A., Benetou V., Trichopoulos D., Masala G., Krogh V., Tumino R., Ricceri F., Panico S., Bueno-de-Mesquita H.B., Monninkhof E.M., May A.M., Weiderpass E., Quiros J.R., Travier N., Molina-Montes E., Amiano P., Huerta J.M., Ardanaz E., Sund M., Johansson M., Khaw K.T., Wareham N., Scalbert A., Gunter M.J., Riboli E., Romieu I.

Cancer Causes Control; 2014; 25(1): 111-124

Abstract as provided by PubMed

PURPOSE: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. METHODS: A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. RESULTS: In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was <2 %. CONCLUSIONS: Our results support the hypothesis of an influence, although small in magnitude, of PA on sex hormone levels in blood, independent of body size

Anthropometric measures and bladder cancer risk: A prospective study in the EPIC cohort

Roswall N., Freisling H., Bueno-de-Mesquita H.B., Ros M., Christensen J., Overvad K., Boutron-Ruault M.C., Severi G., Fagherazzi G., Chang-Claude J., Kaaks R., Steffen A., Boeing H., Arguelles M., Agudo A., Sanchez M.J., Chirlaque M.D., Barricarte Gurrea A., Amiano P., Wareham N., Khaw K.T., Bradbury K.E., Trichopoulou A., Papatesta H.M., Trichopoulos D., Palli D., Pala V., Tumino R., Sacerdote C., Mattiello A., Peeters P.H., Ehrnstrom R., Brennan P., Ferrari P., Ljungberg B., Norat T., Gunter M., Riboli E., Weiderpass E., Halkjaer J.

Int J Cancer; 2014; 135(12): 2918-2929

Abstract as provided by PubMed

Anthropometric measures have been related to risk of several cancers. For bladder cancer, however, evidence is sparse. Comparability of existing studies is hampered by use of different obesity-measures, inadequate control for smoking, and few female cases. This study examined associations between height, weight, waist and hip circumference, waist-hip ratio, waist-height ratio, body mass index (BMI), recalled weight at age 20 and bladder cancer, and investigated effect modification by age, tumor aggressiveness and smoking. The study was conducted in the European Prospective Investigation into Cancer and Nutrition cohort, in 390,878 participants. Associations were calculated using Cox Proportional Hazards Models. During follow-up, 1,391 bladder cancers (1,018 male; 373 female) occurred. Height was unrelated to bladder cancer in both genders. We found a small but significant positive association with weight [1.04 (1.01-1.07) per 5 kilo], BMI [1.05 (1.02-1.08) per 2 units], waist circumference [1.04 (1.01-1.08) per 5 cm], waist-hip ratio (1.07 (1.02-1.13) per 0.05 unit] and waist-height ratio [1.07 (1.01-1.13) per 0.05 unit] in men. Stratification by smoking status confined associations in men to former smokers. In never smokers, we found no significant associations, suggesting residual confounding by smoking. Results did not differ with tumor aggressiveness and age. Residual analyses on BMI/waist circumference showed a significantly higher disease risk with BMI in men (p = 0.01), but no association with waist circumference. In conclusion, in this large study, height was unrelated to bladder cancer, whereas overweight was associated with a slightly higher bladder cancer risk in men. This association may, however, be distorted by residual confounding by smoking

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