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2017

DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility

Ambatipudi S., Horvath S., Perrier F., Cuenin C., Hernandez-Vargas H., Le Calvez-Kelm F., Durand G., Byrnes G., Ferrari P., Bouaoun L., Sklias A., Chajes V., Overvad K., Severi G., Baglietto L., Clavel-Chapelon F., Kaaks R., Barrdahl M., Boeing H., Trichopoulou A., Lagiou P., Naska A., Masala G., Agnoli C., Polidoro S., Tumino R., Panico S., Dolle M., Peeters P. H., Onland-Moret N. C., Sandanger T. M., Nost T. H., Weiderpass E., Quiros J. R., Agudo A., Rodriguez-Barranco M., Huerta Castano J. M., Barricarte A., Fernandez A. M., Travis R. C., Vineis P., Muller D. C., Riboli E., Gunter M., Romieu I., Herceg Z.

Eur J Cancer; 2017; 299-307

PMID:28259012

Abstract as provided by PubMed

AIM OF THE STUDY: A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. METHODS: Here, we profiled DNA methylation changes in a nested case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. RESULTS: We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007-1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007-1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020-1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03-1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. CONCLUSION: Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility.

Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition

Caini S., Masala G., Saieva C., Kvaskoff M., Savoye I., Sacerdote C., Hemmingsson O., Hammer Bech B., Overvad K., Tjonneland A., Petersen K. E., Mancini F. R., Boutron-Ruault M. C., Cervenka I., Kaaks R., Kuhn T., Boeing H., Floegel A., Trichopoulou A., Valanou E., Kritikou M., Tagliabue G., Panico S., Tumino R., Bueno-de-Mesquita H. B., Peeters P. H., Veierod M. B., Ghiasvand R., Lukic M., Quiros J. R., Chirlaque M. D., Ardanaz E., Salamanca Fernandez E., Larranaga N., Zamora-Ros R., Maria Nilsson L., Ljuslinder I., Jirstrom K., Sonestedt E., Key T. J., Wareham N., Khaw K. T., Gunter M., Huybrechts I., Murphy N., Tsilidis K. K., Weiderpass E., Palli D.

Int J Cancer; 2017; 140(10): 2246-2255

PMID:28218395

Abstract as provided by PubMed

In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma.

A metabolomic study of biomarkers of meat and fish intake

Cheung W., Keski-Rahkonen P., Assi N., Ferrari P., Freisling H., Rinaldi S., Slimani N., Zamora-Ros R., Rundle M., Frost G., Gibbons H., Carr E., Brennan L., Cross A. J., Pala V., Panico S., Sacerdote C., Palli D., Tumino R., Kuhn T., Kaaks R., Boeing H., Floegel A., Mancini F., Boutron-Ruault M. C., Baglietto L., Trichopoulou A., Naska A., Orfanos P., Scalbert A.

Am J Clin Nutr; 2017; 105(3): 600-608

PMID:28122782

Abstract as provided by PubMed

Background: Meat and fish intakes have been associated with various chronic diseases. The use of specific biomarkers may help to assess meat and fish intake and improve subject classification according to the amount and type of meat or fish consumed.Objective: A metabolomic approach was applied to search for biomarkers of meat and fish intake in a dietary intervention study and in free-living subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Design: In the dietary intervention study, 4 groups of 10 subjects consumed increasing quantities of chicken, red meat, processed meat, and fish over 3 successive weeks. Twenty-four-hour urine samples were collected during each period and analyzed by high-resolution liquid chromatography-mass spectrometry. Signals characteristic of meat or fish intake were replicated in 50 EPIC subjects for whom a 24-h urine sample and 24-h dietary recall were available and who were selected for their exclusive intake or no intake of any of the 4 same foods.Results: A total of 249 mass spectrometric features showed a positive dose-dependent response to meat or fish intake in the intervention study. Eighteen of these features best predicted intake of the 4 food groups in the EPIC urine samples on the basis of partial receiver operator curve analyses with permutation testing (areas under the curve ranging between 0.61 and 1.0). Of these signals, 8 metabolites were identified. Anserine was found to be specific for chicken intake, whereas trimethylamine-N-oxide showed good specificity for fish. Carnosine and 3 acylcarnitines (acetylcarnitine, propionylcarnitine, and 2-methylbutyrylcarnitine) appeared to be more generic indicators of meat and meat and fish intake, respectively.Conclusion: The meat and fish biomarkers identified in this work may be used to study associations between meat and fish intake and disease risk in epidemiologic studies. This trial was registered at clinicaltrials.gov as NCT01684917.

Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort

Fortner R. T., Sarink D., Schock H., Johnson T., Tjonneland A., Olsen A., Overvad K., Affret A., His M., Boutron-Ruault M. C., Boeing H., Trichopoulou A., Naska A., Orfanos P., Palli D., Sieri S., Mattiello A., Tumino R., Ricceri F., Bueno-de-Mesquita H. B., Peeters P. H., Van Gils C. H., Weiderpass E., Lund E., Quiros J. R., Agudo A., Sanchez M. J., Chirlaque M. D., Ardanaz E., Dorronsoro M., Key T., Khaw K. T., Rinaldi S., Dossus L., Gunter M., Merritt M. A., Riboli E., Kaaks R.

BMC Med; 2017; 15(1): 26

PMID:28173834

Abstract as provided by PubMed

BACKGROUND: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study. METHODS: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER-, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. RESULTS: The associations between OPG and ER+ and ER- breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER- breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24-3.02]; p trend = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER- disease did not differ by menopausal status at blood collection (p het = 0.97), and we observed no heterogeneity by HT use at blood collection (p het >/= 0.43) or age at breast cancer diagnosis (p het >/= 0.30). CONCLUSIONS: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER- breast cancer.

Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort

Fortner R. T., Husing A., Kuhn T., Konar M., Overvad K., Tjonneland A., Hansen L., Boutron-Ruault M. C., Severi G., Fournier A., Boeing H., Trichopoulou A., Benetou V., Orfanos P., Masala G., Agnoli C., Mattiello A., Tumino R., Sacerdote C., Bueno-de-Mesquita H. B., Peeters P. H., Weiderpass E., Gram I. T., Gavrilyuk O., Quiros J. R., Maria Huerta J., Ardanaz E., Larranaga N., Lujan-Barroso L., Sanchez-Cantalejo E., Butt S. T., Borgquist S., Idahl A., Lundin E., Khaw K. T., Allen N. E., Rinaldi S., Dossus L., Gunter M., Merritt M. A., Tzoulaki I., Riboli E., Kaaks R.

Int J Cancer; 2017; 140(6): 1317-1323

PMID:27935083

Abstract as provided by PubMed

Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p < 0.157 indicating improvement in the Akaike information criterion (AIC). Improvement in discrimination was assessed using the C-statistic for all biomarkers alone, and change in C-statistic from addition of biomarkers to preexisting absolute risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were selected into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including etiologic markers on independent pathways and genetic markers may further improve discrimination.

Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models: results from the EPIC cohort

Fortner R. T., Vitonis A. F., Schock H., Husing A., Johnson T., Fichorova R. N., Fashemi T., Yamamoto H. S., Tjonneland A., Hansen L., Overvad K., Boutron-Ruault M. C., Kvaskoff M., Severi G., Boeing H., Trichopoulou A., Benetou V., La Vecchia C., Palli D., Sieri S., Tumino R., Matullo G., Mattiello A., Onland-Moret N. C., Peeters P. H., Weiderpass E., Gram I. T., Jareid M., Quiros J. R., Duell E. J., Sanchez M. J., Chirlaque M. D., Ardanaz E., Larranaga N., Nodin B., Brandstedt J., Idahl A., Khaw K. T., Allen N., Gunter M., Johansson M., Dossus L., Merritt M. A., Riboli E., Cramer D. W., Kaaks R., Terry K. L.

J Ovarian Res; 2017; 10(1): 20

PMID:28320479

Abstract as provided by PubMed

BACKGROUND: Ovarian cancer early detection markers CA125, CA15.3, HE4, and CA72.4 vary between healthy women, limiting their utility for screening. METHODS: We evaluated cross-sectional relationships between lifestyle and reproductive factors and these markers among controls (n = 1910) from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Improvements in discrimination of prediction models adjusting for correlates of the markers were evaluated among postmenopausal women in the nested case-control study (n = 590 cases). Generalized linear models were used to calculate geometric means of CA125, CA15.3, and HE4. CA72.4 above vs. below limit of detection was evaluated using logistic regression. Early detection prediction was modeled using conditional logistic regression. RESULTS: CA125 concentrations were lower, and CA15.3 higher, in post- vs. premenopausal women (p </= 0.02). Among postmenopausal women, CA125 was higher among women with higher parity and older age at menopause (ptrend </= 0.02), but lower among women reporting oophorectomy, hysterectomy, ever use of estrogen-only hormone therapy, or current smoking (p < 0.01). CA15.3 concentrations were higher among heavier women and in former smokers (p </= 0.03). HE4 was higher with older age at blood collection and in current smokers, and inversely associated with OC use duration, parity, and older age at menopause (</= 0.02). No associations were observed with CA72.4. Adjusting for correlates of the markers in prediction models did not improve the discrimination. CONCLUSIONS: This study provides insights into sources of variation in ovarian cancer early detection markers in healthy women and informs about the utility of individualizing marker cutpoints based on epidemiologic factors.

Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: A nested case-control study

Huang J., Zagai U., Hallmans G., Nyren O., Engstrand L., Stolzenberg-Solomon R., Duell E. J., Overvad K., Katzke V. A., Kaaks R., Jenab M., Park J. Y., Murillo R., Trichopoulou A., Lagiou P., Bamia C., Bradbury K. E., Riboli E., Aune D., Tsilidis K. K., Capella G., Agudo A., Krogh V., Palli D., Panico S., Weiderpass E., Tjonneland A., Olsen A., Martinez B., Redondo-Sanchez D., Chirlaque M. D., Hm Peeters P., Regner S., Lindkvist B., Naccarati A., Ardanaz E., Larranaga N., Boutron-Ruault M. C., Rebours V., Barre A., Bueno-de-Mesquita H. B., Ye W.

Int J Cancer; 2017; 140(8): 1727-1735

PMID:28032715

Abstract as provided by PubMed

The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms.

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort

Matejcic M., de Batlle J., Ricci C., Biessy C., Perrier F., Huybrechts I., Weiderpass E., Boutron-Ruault M. C., Cadeau C., His M., Cox D. G., Boeing H., Fortner R. T., Kaaks R., Lagiou P., Trichopoulou A., Benetou V., Tumino R., Panico S., Sieri S., Palli D., Ricceri F., Bueno-de-Mesquita H. B., Skeie G., Amiano P., Sanchez M. J., Chirlaque M. D., Barricarte A., Quiros J. R., Buckland G., van Gils C. H., Peeters P. H., Key T. J., Riboli E., Gylling B., Zeleniuch-Jacquotte A., Gunter M. J., Romieu I., Chajes V.

Int J Cancer; 2017; 140(6): 1246-1259

PMID:27905104

Abstract as provided by PubMed

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort

Molina-Montes E., Sanchez M. J., Buckland G., Bueno-de-Mesquita H. B., Weiderpass E., Amiano P., Wark P. A., Kuhn T., Katzke V., Huerta J. M., Ardanaz E., Quiros J. R., Affret A., His M., Boutron-Ruault M. C., Peeters P. H., Ye W., Sund M., Boeing H., Iqbal K., Ohlsson B., Sonestedt E., Tjonneland A., Petersen K. E., Travis R. C., Skeie G., Agnoli C., Panico S., Palli D., Tumino R., Sacerdote C., Freisling H., Huybrechts I., Overvad K., Trichopoulou A., Bamia C., Vasilopoulou E., Wareham N., Khaw K. T., Cross A. J., Ward H. A., Riboli E., Duell E. J.

Br J Cancer; 2017; 116(6): 811-820

PMID:28170373

Abstract as provided by PubMed

BACKGROUND: The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Over half a million participants from 10 European countries were followed up for over 11 years, after which 865 newly diagnosed exocrine pancreatic cancer cases were identified. Adherence to the MD was estimated through an adapted score without the alcohol component (arMED) to discount alcohol-related harmful effects. Cox proportional hazards regression models, stratified by age, sex and centre, and adjusted for energy intake, body mass index, smoking status, alcohol intake and diabetes status at recruitment, were used to estimate hazard ratios (HRs) associated with pancreatic cancer and their corresponding 95% confidence intervals (CIs). RESULTS: Adherence to the arMED score was not associated with risk of pancreatic cancer (HR high vs low adherence=0.99; 95% CI: 0.77-1.26, and HR per increments of two units in adherence to arMED=1.00; 95% CI: 0.94-1.06). There was no convincing evidence for heterogeneity by smoking status, body mass index, diabetes or European region. There was also no evidence of significant associations in analyses involving microscopically confirmed cases, plausible reporters of energy intake or other definitions of the MD pattern. CONCLUSIONS: A high adherence to the MD is not associated with pancreatic cancer risk in the EPIC study.

Dietary and lifestyle determinants of acrylamide and glycidamide hemoglobin adducts in non-smoking postmenopausal women from the EPIC cohort

Obon-Santacana M., Lujan-Barroso L., Freisling H., Cadeau C., Fagherazzi G., Boutron-Ruault M. C., Kaaks R., Fortner R. T., Boeing H., Ramon Quiros J., Molina-Montes E., Chamosa S., Castano J. M., Ardanaz E., Khaw K. T., Wareham N., Key T., Trichopoulou A., Lagiou P., Naska A., Palli D., Grioni S., Tumino R., Vineis P., De Magistris M. S., Bueno-de-Mesquita H. B., Peeters P. H., Wennberg M., Bergdahl I. A., Vesper H., Riboli E., Duell E. J.

Eur J Nutr; 2017; 56(3): 1157-1168

PMID:26850269

Abstract as provided by PubMed

PURPOSE: Acrylamide was classified as 'probably carcinogenic' to humans in 1994 by the International Agency for Research on Cancer. In 2002, public health concern increased when acrylamide was identified in starchy, plant-based foods, processed at high temperatures. The purpose of this study was to identify which food groups and lifestyle variables were determinants of hemoglobin adduct concentrations of acrylamide (HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women from eight countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) . In this cross-sectional analysis, four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA) and all independent variables were log-transformed (log2) to improve normality. Median (25th-75th percentile) HbAA and HbGA adduct levels were 41.3 (32.8-53.1) pmol/g Hb and 34.2 (25.4-46.9) pmol/g Hb, respectively. RESULTS: The main food group determinants of HbAA, HbGA, and HbAA + HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA explained in this study was 30, 26, 29, and 13 %, respectively. CONCLUSIONS: Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort.

Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Perez-Cornago A., Appleby P. N., Tipper S., Key T. J., Allen N. E., Nieters A., Vermeulen R., Roulland S., Casabonne D., Kaaks R., Fortner R. T., Boeing H., Trichopoulou A., La Vecchia C., Klinaki E., Hansen L., Tjonneland A., Bonnet F., Fagherazzi G., Boutron-Ruault M. C., Pala V., Masala G., Sacerdote C., Peeters P. H., Bueno-de-Mesquita H. B., Weiderpass E., Dorronsoro M., Quiros J. R., Barricarte A., Gavrila D., Agudo A., Borgquist S., Rosendahl A. H., Melin B., Wareham N., Khaw K. T., Gunter M., Riboli E., Vineis P., Travis R. C.

Int J Cancer; 2017; 140(5): 1111-1118

PMID:27870006

Abstract as provided by PubMed

Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested case-control study of 1,072 cases of lymphoid malignancies and 1,072 individually matched controls from the European Prospective Investigation into Cancer and Nutrition. Odds ratios (ORs) and confidence intervals (CIs) for lymphoma were calculated using conditional logistic regression. IGF-I concentration was not associated with overall lymphoma risk (multivariable-adjusted OR for highest versus lowest third = 0.77 [95% CI = 0.57-1.03], ptrend = 0.06). There was no statistical evidence of heterogeneity in this association with IGF-I by sex, age at blood collection, time between blood collection and diagnosis, age at diagnosis, or body mass index (pheterogeneity for all >/= 0.05). There were no associations between IGF-I concentration and risk for specific BCL subtypes, T-cell lymphoma or Hodgkin lymphoma, although number of cases were small. In this European population, IGF-I concentration was not associated with risk of overall lymphoma. This study provides the first prospective evidence on circulating IGF-I concentrations and risk of lymphoma. Further prospective data are required to examine associations of IGF-I concentrations with lymphoma subtypes.

Fiber intake modulates the association of alcohol intake with breast cancer

Romieu I., Ferrari P., Chajes V., de Batlle J., Biessy C., Scoccianti C., Dossus L., Christine Boutron M., Bastide N., Overvad K., Olsen A., Tjonneland A., Kaaks R., Boeing H., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Sieri S., Tumino R., Vineis P., Panico S., Bueno-de-Mesquita H. B., Gils C. H., Peeters P. H., Lund E., Skeie G., Weiderpass E., Ramon Quiros J., Chirlaque M. D., Ardanaz E., Sanchez M. J., Duell E. J., Amiano Etxezarreta P., Borgquist S., Hallmans G., Johansson I., Maria Nilsson L., Khaw K. T., Wareham N., Key T. J., Travis R. C., Murphy N., Wark P. A., Riboli E.

Int J Cancer; 2017; 140(2): 316-321

PMID:27599758

Abstract as provided by PubMed

Alcohol intake has been related to an increased risk of breast cancer (BC) while dietary fiber intake has been inversely associated to BC risk. A beneficial effect of fibers on ethanol carcinogenesis through their impact on estrogen levels is still controversial. We investigated the role of dietary fiber as a modifying factor of the association of alcohol and BC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 334,850 women aged 35-70 years at baseline enrolled in the ten countries of the EPIC study and followed up for 11.0 years on average. Information on fiber and alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. Hazard ratios (HR) of developing invasive BC according to different levels of alcohol and fiber intake were computed. During 3,670,439 person-years, 11,576 incident BC cases were diagnosed. For subjects with low intake of fiber (<18.5 g/day), the risk of BC per 10 g/day of alcohol intake was 1.06 (1.03-1.08) while among subjects with high intake of fiber (>24.2 g/day) the risk of BC was 1.02 (0.99-1.05) (test for interaction p = 0.011). This modulating effect was stronger for fiber from vegetables. Our results suggest that fiber intake may modulate the positive association of alcohol intake and BC. Alcohol is well known to increase the risk for BC, while a fiber-rich diet has the opposite effect. Here the authors find a significant interaction between both lifestyle factors indicating that high fiber intake can ease the adverse effects associated with alcohol consumption. Consequently, women with high alcohol intake and low fiber intake (<18.5 g/day) had the highest risk for BC. Specific benefits were associated with fibers from vegetable, warranting further investigations into specific fiber sources and their mechanistic interactions with alcohol-induced BC risk.

The association between adult attained height and sitting height with mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Sawada N., Wark P. A., Merritt M. A., Tsugane S., Ward H. A., Rinaldi S., Weiderpass E., Dartois L., His M., Boutron-Ruault M. C., Turzanski-Fortner R., Kaaks R., Overvad K., Redondo M. L., Travier N., Molina-Portillo E., Dorronsoro M., Cirera L., Ardanaz E., Perez-Cornago A., Trichopoulou A., Lagiou P., Valanou E., Masala G., Pala V., Hm Peeters P., T. van der Schouw Y, Melander O., Manjer J., da Silva M., Skeie G., Tjonneland A., Olsen A., J. Gunter M, Riboli E., J. Cross A

PLoS ONE; 2017; 12(3): e0173117

PMID:28257491

Abstract as provided by PubMed

Adult height and sitting height may reflect genetic and environmental factors, including early life nutrition, physical and social environments. Previous studies have reported divergent associations for height and chronic disease mortality, with positive associations observed for cancer mortality but inverse associations for circulatory disease mortality. Sitting height might be more strongly associated with insulin resistance; however, data on sitting height and mortality is sparse. Using the European Prospective Investigation into Cancer and Nutrition study, a prospective cohort of 409,748 individuals, we examined adult height and sitting height in relation to all-cause and cause-specific mortality. Height was measured in the majority of participants; sitting height was measured in ~253,000 participants. During an average of 12.5 years of follow-up, 29,810 deaths (11,931 from cancer and 7,346 from circulatory disease) were identified. Hazard ratios (HR) with 95% confidence intervals (CI) for death were calculated using multivariable Cox regression within quintiles of height. Height was positively associated with cancer mortality (men: HRQ5 vs. Q1 = 1.11, 95%CI = 1.00-1.24; women: HRQ5 vs. Q1 = 1.17, 95%CI = 1.07-1.28). In contrast, height was inversely associated with circulatory disease mortality (men: HRQ5 vs. Q1 = 0.63, 95%CI = 0.56-0.71; women: HRQ5 vs. Q1 = 0.81, 95%CI = 0.70-0.93). Although sitting height was not associated with cancer mortality, it was inversely associated with circulatory disease (men: HRQ5 vs. Q1 = 0.64, 95%CI = 0.55-0.75; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.49-0.74) and respiratory disease mortality (men: HRQ5 vs. Q1 = 0.45, 95%CI = 0.28-0.71; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.40-0.89). We observed opposing effects of height on cancer and circulatory disease mortality. Sitting height was inversely associated with circulatory disease and respiratory disease mortality.

Vasectomy and Prostate Cancer Risk in the European Prospective Investigation Into Cancer and Nutrition (EPIC)

Smith K., Byrne, Castano J. M., Chirlaque M. D., Lilja H., Agudo A., Ardanaz E., Rodriguez-Barranco M., Boeing H., Kaaks R., Khaw K. T., Larranaga N., Navarro C., Olsen A., Overvad K., Perez-Cornago A., Rohrmann S., Sanchez M. J., Tjonneland A., Tsilidis K. K., Johansson M., Riboli E., Key T. J., Travis R. C.

J Clin Oncol; 2017; 35(12): 1297-1303

PMID:28375714

Abstract as provided by PubMed

Purpose Vasectomy is a commonly used form of male sterilization, and some studies have suggested that it may be associated with an increased risk of prostate cancer, including more aggressive forms of the disease. We investigated the prospective association of vasectomy with prostate cancer in a large European cohort, with a focus on high-grade and advanced-stage tumors, and death due to prostate cancer. Patients and Methods A total of 84,753 men from the European Prospective Investigation into Cancer and Nutrition (EPIC), aged 35 to 79 years, provided information on vasectomy status (15% with vasectomy) at recruitment and were followed for incidence of prostate cancer and death. We estimated the association of vasectomy with prostate cancer risk overall, by tumor subtype, and for death due to prostate cancer, using multivariable-adjusted Cox proportional hazards models. Results During an average follow-up of 15.4 years, 4,377 men were diagnosed with prostate cancer, including 641 who had undergone a vasectomy. Vasectomy was not associated with prostate cancer risk (hazard ratio [HR], 1.05; 95% CI, 0.96 to 1.15), and no evidence for heterogeneity in the association was observed by stage of disease or years since vasectomy. There was some evidence of heterogeneity by tumor grade ( P = .02), with an increased risk for low-intermediate grade (HR, 1.14; 95% CI, 1.01 to 1.29) but not high-grade prostate cancer (HR, 0.83; 95% CI, 0.64 to 1.07). Vasectomy was not associated with death due to prostate cancer (HR, 0.88; 95% CI, 0.68 to 1.12). Conclusion These findings from a large European prospective study show no elevated risk for overall, high-grade or advanced-stage prostate cancer, or death due to prostate cancer in men who have undergone a vasectomy compared with men who have not.

Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans

Stepien M., Hughes D. J., Hybsier S., Bamia C., Tjonneland A., Overvad K., Affret A., His M., Boutron-Ruault M. C., Katzke V., Kuhn T., Aleksandrova K., Trichopoulou A., Lagiou P., Orfanos P., Palli D., Sieri S., Tumino R., Ricceri F., Panico S., Bueno-de-Mesquita H. B., Peeters P. H., Weiderpass E., Lasheras C., Bonet Bonet C., Molina-Portillo E., Dorronsoro M., Huerta J. M., Barricarte A., Ohlsson B., Sjoberg K., Werner M., Shungin D., Wareham N., Khaw K. T., Travis R. C., Freisling H., Cross A. J., Schomburg L., Jenab M.

Br J Cancer; 2017; 116(5): 688-696

PMID:28152549

Abstract as provided by PubMed

BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers. METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk. RESULTS: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed. CONCLUSIONS: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort

Zamora-Ros R., Barupal D. K., Rothwell J. A., Jenab M., Fedirko V., Romieu I., Aleksandrova K., Overvad K., Kyro C., Tjonneland A., Affret A., His M., Boutron-Ruault M. C., Katzke V., Kuhn T., Boeing H., Trichopoulou A., Naska A., Kritikou M., Saieva C., Agnoli C., Santucci de Magistris M., Tumino R., Fasanelli F., Weiderpass E., Skeie G., Merino S., Jakszyn P., Sanchez M. J., Dorronsoro M., Navarro C., Ardanaz E., Sonestedt E., Ericson U., Maria Nilsson L., Boden S., Bueno-de-Mesquita H. B., Peeters P. H., Perez-Cornago A., Wareham N. J., Khaw K. T., Freisling H., Cross A. J., Riboli E., Scalbert A.

Int J Cancer; 2017; 140(8): 1836-1844

PMID:28006847

Abstract as provided by PubMed

Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre-specific validated dietary questionnaires and composition data from the Phenol-Explorer database. During an average of 11 years of follow-up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93-1.18; p-trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development.

2016

A method for sensitivity analysis to assess the effects of measurement error in multiple exposure variables using external validation data

Agogo G. O., van der Voet H., van 't Veer P., Ferrari P., Muller D. C., Sanchez-Cantalejo E., Bamia C., Braaten T., Knuppel S., Johansson I., van Eeuwijk F. A., Boshuizen H. C.

BMC Med Res Methodol; 2016; 16(1): 139

PMID:27737637

Abstract as provided by PubMed

BACKGROUND: Measurement error in self-reported dietary intakes is known to bias the association between dietary intake and a health outcome of interest such as risk of a disease. The association can be distorted further by mismeasured confounders, leading to invalid results and conclusions. It is, however, difficult to adjust for the bias in the association when there is no internal validation data. METHODS: We proposed a method to adjust for the bias in the diet-disease association (hereafter, association), due to measurement error in dietary intake and a mismeasured confounder, when there is no internal validation data. The method combines prior information on the validity of the self-report instrument with the observed data to adjust for the bias in the association. We compared the proposed method with the method that ignores the confounder effect, and with the method that ignores measurement errors completely. We assessed the sensitivity of the estimates to various magnitudes of measurement error, error correlations and uncertainty in the literature-reported validation data. We applied the methods to fruits and vegetables (FV) intakes, cigarette smoking (confounder) and all-cause mortality data from the European Prospective Investigation into Cancer and Nutrition study. RESULTS: Using the proposed method resulted in about four times increase in the strength of association between FV intake and mortality. For weakly correlated errors, measurement error in the confounder minimally affected the hazard ratio estimate for FV intake. The effect was more pronounced for strong error correlations. CONCLUSIONS: The proposed method permits sensitivity analysis on measurement error structures and accounts for uncertainties in the reported validity coefficients. The method is useful in assessing the direction and quantifying the magnitude of bias in the association due to measurement errors in the confounders.

A treelet transform analysis to relate nutrient patterns to the risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Assi N., Moskal A., Slimani N., Viallon V., Chajes V., Freisling H., Monni S., Knueppel S., Forster J., Weiderpass E., Lujan-Barroso L., Amiano P., Ardanaz E., Molina-Montes E., Salmeron D., Quiros J. R., Olsen A., Tjonneland A., Dahm C. C., Overvad K., Dossus L., Fournier A., Baglietto L., Fortner R. T., Kaaks R., Trichopoulou A., Bamia C., Orfanos P., De Magistris M. S., Masala G., Agnoli C., Ricceri F., Tumino R., Bueno de Mesquita H. B., Bakker M. F., Peeters P. H., Skeie G., Braaten T., Winkvist A., Johansson I., Khaw K. T., Wareham N. J., Key T., Travis R., Schmidt J. A., Merritt M. A., Riboli E., Romieu I., Ferrari P.

Public Health Nutr; 2016; 19(2): 242-54

PMID:25702596

Abstract as provided by PubMed

OBJECTIVE: Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology. DESIGN: Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison. SETTING: The European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: Women (n 334 850) from the EPIC study. RESULTS: The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in beta-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0.89, 95 % CI 0.83, 0.95, P trend<0.01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0.89, 95 % CI 0.81, 0.98, P trend=0.02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0.87, 95 % CI 0.77, 0.98, P trend<0.01). CONCLUSIONS: TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.

Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort

Bakker M. F., Peeters P. H., Klaasen V. M., Bueno-de-Mesquita H. B., Jansen E. H., Ros M. M., Travier N., Olsen A., Tjonneland A., Overvad K., Rinaldi S., Romieu I., Brennan P., Boutron-Ruault M. C., Perquier F., Cadeau C., Boeing H., Aleksandrova K., Kaaks R., Kuhn T., Trichopoulou A., Lagiou P., Trichopoulos D., Vineis P., Krogh V., Panico S., Masala G., Tumino R., Weiderpass E., Skeie G., Lund E., Quiros J. R., Ardanaz E., Navarro C., Amiano P., Sanchez M. J., Buckland G., Ericson U., Sonestedt E., Johansson M., Sund M., Travis R. C., Key T. J., Khaw K. T., Wareham N., Riboli E., van Gils C. H.

Am J Clin Nutr; 2016; 103(2): 454-64

PMID:26791185

Abstract as provided by PubMed

BACKGROUND: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity. OBJECTIVE: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer. DESIGN: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin, retinol, alpha-tocopherol, gamma-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided. RESULTS: In quintile 5 compared with quintile 1, alpha-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and beta-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for beta-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution). CONCLUSION: Our results indicate that higher concentrations of plasma beta-carotene and alpha-carotene are associated with lower breast cancer risk of ER- tumors.

The association of substituting carbohydrates with total fat and different types of fatty acids with mortality and weight change among diabetes patients

Campmans-Kuijpers M. J., Sluijs I., Nothlings U., Freisling H., Overvad K., Boeing H., Masala G., Panico S., Tumino R., Sieri S., Johansson I., Winkvist A., Katzke V. A., Kuehn T., Nilsson P. M., Halkjaer J., Tjonneland A., Spijkerman A. M., Arriola L., Sacerdote C., Barricarte A., May A. M., Beulens J. W.

Clin Nutr; 2016; 35(5): 1096-102

PMID:26342536

Abstract as provided by PubMed

BACKGROUND: Substitution of carbohydrates with fat in a diet for type 2 diabetes patients is still debated. OBJECTIVE: This study aimed to investigate the association between dietary carbohydrate intake and isocaloric substitution with (i) total fat, (ii) saturated fatty acids (SFA), (iii) mono-unsaturated fatty acids (MUFA) and (iv) poly-unsaturated fatty acids (PUFA) with all-cause and cardiovascular (CVD) mortality risk and 5-year weight change in patients with type 2 diabetes. METHODS: The study included 6192 patients with type 2 diabetes from 15 cohorts of the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at recruitment with country-specific food-frequency questionnaires. Cox and linear regression were used to estimate the associations with (CVD) mortality and weight change, adjusting for confounders and using different methods to adjust for energy intake. RESULTS: After a mean follow-up of 9.2 y +/- SD 2.3 y, 791 (13%) participants had died, of which 268 (4%) due to CVD. Substituting 10 g or 5 energy% of carbohydrates by total fat was associated with a higher all-cause mortality risk (HR 1.07 [1.02-1.13]), or SFAs (HR 1.25 [1.11-1.40]) and a lower risk when replaced by MUFAs (HR 0.89 [0.77-1.02]). When carbohydrates were substituted with SFAs (HR 1.22 [1.00-1.49]) or PUFAs (HR 1.29 [1.02-1.63]) CVD mortality risk increased. The 5-year weight was lower when carbohydrates were substituted with total fat or MUFAs. These results were consistent over different energy adjustment methods. CONCLUSIONS: In diabetes patients, substitution of carbohydrates with SFAs was associated with a higher (CVD) mortality risk and substitution by total fat was associated with a higher all-cause mortality risk. Substitution of carbohydrates with MUFAs may be associated with lower mortality risk and weight reduction. Instead of promoting replacement of carbohydrates by total fat, dietary guideline should continue focusing on replacement by fat-subtypes; especially SFAs by MUFAs.

Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

Duarte-Salles T., Misra S., Stepien M., Plymoth A., Muller D., Overvad K., Olsen A., Tjonneland A., Baglietto L., Severi G., Boutron-Ruault M. C., Turzanski-Fortner R., Kaaks R., Boeing H., Aleksandrova K., Trichopoulou A., Lagiou P., Bamia C., Pala V., Palli D., Mattiello A., Tumino R., Naccarati A., Bueno-de-Mesquita H. B., Peeters P. H., Weiderpass E., Quiros J. R., Agudo A., Sanchez-Cantalejo E., Ardanaz E., Gavrila D., Dorronsoro M., Werner M., Hemmingsson O., Ohlsson B., Sjoberg K., Wareham N. J., Khaw K. T., Bradbury K. E., Gunter M. J., Cross A. J., Riboli E., Jenab M., Hainaut P., Beretta L.

Cancer Prev Res (Phila); 2016; 9(9): 758-65

PMID:27339170

Abstract as provided by PubMed

We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and alpha-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14-1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis. Cancer Prev Res; 9(9); 758-65. (c)2016 AACR.

Vegetable and fruit consumption and the risk of hormone receptor-defined breast cancer in the EPIC cohort

Emaus M. J., Peeters P. H., Bakker M. F., Overvad K., Tjonneland A., Olsen A., Romieu I., Ferrari P., Dossus L., Boutron-Ruault M. C., Baglietto L., Fortner R. T., Kaaks R., Boeing H., Trichopoulou A., Lagiou P., Trichopoulos D., Masala G., Pala V., Panico S., Tumino R., Polidoro S., Skeie G., Lund E., Weiderpass E., Quiros J. R., Travier N., Sanchez M. J., Chirlaque M. D., Ardanaz E., Dorronsoro M., Winkvist A., Wennberg M., Bueno-de-Mesquita H. B., Khaw K. T., Travis R. C., Key T. J., Aune D., Gunter M., Riboli E., van Gils C. H.

Am J Clin Nutr; 2016; 103(1): 168-77

PMID:26607934

Abstract as provided by PubMed

BACKGROUND: The recent literature indicates that a high vegetable intake and not a high fruit intake could be associated with decreased steroid hormone receptor-negative breast cancer risk. OBJECTIVE: This study aimed to investigate the association between vegetable and fruit intake and steroid hormone receptor-defined breast cancer risk. DESIGN: A total of 335,054 female participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in this study (mean +/- SD age: 50.8 +/- 9.8 y). Vegetable and fruit intake was measured by country-specific questionnaires filled out at recruitment between 1992 and 2000 with the use of standardized procedures. Cox proportional hazards models were stratified by age at recruitment and study center and were adjusted for breast cancer risk factors. RESULTS: After a median follow-up of 11.5 y (IQR: 10.1-12.3 y), 10,197 incident invasive breast cancers were diagnosed [3479 estrogen and progesterone receptor positive (ER+PR+); 1021 ER and PR negative (ER-PR-)]. Compared with the lowest quintile, the highest quintile of vegetable intake was associated with a lower risk of overall breast cancer (HRquintile 5-quintile 1: 0.87; 95% CI: 0.80, 0.94). Although the inverse association was most apparent for ER-PR- breast cancer (ER-PR-: HRquintile 5-quintile 1: 0.74; 95% CI: 0.57, 0.96; P-trend = 0.03; ER+PR+: HRquintile 5-quintile 1: 0.91; 95% CI: 0.79, 1.05; P-trend = 0.14), the test for heterogeneity by hormone receptor status was not significant (P-heterogeneity = 0.09). Fruit intake was not significantly associated with total and hormone receptor-defined breast cancer risk. CONCLUSION: This study supports evidence that a high vegetable intake is associated with lower (mainly hormone receptor-negative) breast cancer risk.

Circulating vitamin D in relation to cancer incidence and survival of the head and neck and oesophagus in the EPIC cohort

Fanidi A., Muller D. C., Midttun O., Ueland P. M., Vollset S. E., Relton C., Vineis P., Weiderpass E., Skeie G., Brustad M., Palli D., Tumino R., Grioni S., Sacerdote C., Bueno-de-Mesquita H. B., Peeters P. H., Boutron-Ruault M. C., Kvaskoff M., Cadeau C., Huerta J. M., Sanchez M. J., Agudo A., Lasheras C., Quiros J. R., Chamosa S., Riboli E., Travis R. C., Ward H., Murphy N., Khaw K. T., Trichopoulou A., Lagiou P., Papatesta E. M., Boeing H., Kuehn T., Katzke V., Steffen A., Johansson A., Brennan P., Johansson M.

Sci Rep; 2016; 36017

PMID:27812016

Abstract as provided by PubMed

Experimental and epidemiological data suggest that vitamin D play a role in pathogenesis and progression of cancer, but prospective data on head and neck cancer (HNC) and oesophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants with blood samples between 1992 and 2000. This analysis includes 497 case-control pairs of the head and neck and oesophagus, as well as 443 additional controls. Circulating 25(OH)D3 were measured in pre-diagnostic samples and evaluated in relation to HNC and oesophagus cancer risk and post-diagnosis all-cause mortality. After controlling for risk factors, a doubling of 25(OH)D3 was associated with 30% lower odds of HNC (OR 0.70, 95% confidence interval [95% CI] 0.56-0.88, Ptrend = 0.001). Subsequent analyses by anatomical sub-site indicated clear inverse associations with risk of larynx and hypopharynx cancer combined (OR 0.55, 95CI% 0.39-0.78) and oral cavity cancer (OR 0.60, 95CI% 0.42-0.87). Low 25(OH)D3 concentrations were also associated with higher risk of death from any cause among HNC cases. No clear association was seen with risk or survival for oesophageal cancer. Study participants with elevated circulating concentrations of 25(OH)D3 had decreased risk of HNC, as well as improved survival following diagnosis.

Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study

Forouhi N. G., Imamura F., Sharp S. J., Koulman A., Schulze M. B., Zheng J., Ye Z., Sluijs I., Guevara M., Huerta J. M., Kroger J., Wang L. Y., Summerhill K., Griffin J. L., Feskens E. J., Affret A., Amiano P., Boeing H., Dow C., Fagherazzi G., Franks P. W., Gonzalez C., Kaaks R., Key T. J., Khaw K. T., Kuhn T., Mortensen L. M., Nilsson P. M., Overvad K., Pala V., Palli D., Panico S., Quiros J. R., Rodriguez-Barranco M., Rolandsson O., Sacerdote C., Scalbert A., Slimani N., Spijkerman A. M., Tjonneland A., Tormo M. J., Tumino R., van der A. Dl, van der Schouw Y. T., Langenberg C., Riboli E., Wareham N. J.

PLoS Med; 2016; 13(7): e1002094

PMID:27434045

Abstract as provided by PubMed

BACKGROUND: Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. METHODS AND FINDINGS: Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, alpha-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with gamma-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. CONCLUSIONS: These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.

Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study

Gallo V., Vanacore N., Bueno-de-Mesquita H. B., Vermeulen R., Brayne C., Pearce N., Wark P. A., Ward H. A., Ferrari P., Jenab M., Andersen P. M., Wennberg P., Wareham N., Katzke V., Kaaks R., Weiderpass E., Peeters P. H., Mattiello A., Pala V., Barricante A., Chirlaque M. D., Travier N., Travis R. C., Sanchez M. J., Pessah-Rasmussen H., Petersson J., Tjonneland A., Tumino R., Quiros J. R., Trichopoulou A., Kyrozis A., Oikonomidou D., Masala G., Sacerdote C., Arriola L., Boeing H., Vigl M., Claver-Chapelon F., Middleton L., Riboli E., Vineis P.

Eur J Epidemiol; 2016; 31(3): 255-66

PMID:26968841

Abstract as provided by PubMed

Previous case-control studies have suggested a possible increased risk of Amyotrophic Lateral Sclerosis (ALS) with physical activity (PA), but this association has never been studied in prospective cohort studies. We therefore assessed the association between PA and risk of death from ALS in the European Prospective Investigation into Cancer and Nutrition. A total of 472,100 individuals were included in the analysis, yielding 219 ALS deaths. At recruitment, information on PA was collected thorough standardised questionnaires. Total PA was expressed by the Cambridge Physical Activity Index (CPAI) and analysed in relation to ALS mortality, using Cox hazard models. Interactions with age, sex, and anthropometric measures were assessed. Total PA was weakly inversely associated with ALS mortality with a borderline statistically significant trend across categories (p = 0.042), with those physically active being 33% less likely to die from ALS compared to those inactive: HR = 0.67 (95% CI 0.42-1.06). Anthropometric measures, sex, and age did not modify the association with CPAI. The present study shows a slightly decreased-not increased like in case-control studies-risk of dying from ALS in those with high levels of total PA at enrolment. This association does not appear confounded by age, gender, anthropometry, smoking, and education. Ours was the first prospective cohort study on ALS and physical activity.

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