Dietary intake and biomarkers of acrylamide exposure and risk of endometrial and ovarian cancer: A molecular epidemiologic study in the European Prospective Investigation into Cancer and Nutrition

Abstract

[eng] Acrylamide is an organic chemical that has several important uses in industry, such as a flocculant in public water supplies, and in biomedical research. In 1994, acrylamide was classified by the International Agency for Research on Cancer as ‘probably carcinogenic’ to humans. In 2002, acrylamide was discovered in some starchy foods that are cooked at high temperature (e.g., potato crisps and chips). Acrylamide also is a common component of cigarette smoke. From 2006-2010, epidemiologic studies began to examine and report on the possible association between dietary acrylamide intake and risk of human cancer, including ovarian and endometrial cancers (two of which suggested possible associations). Endometrial and ovarian are the fourth and fifth most common cancers diagnosed in European women. The general aim of this thesis was to assess the risk of endometrial cancer (EC) and epithelial ovarian (EOC) cancer in relation to dietary acrylamide exposure based on questionnaire information and biomarkers of internal exposure. The study population for this project was 368,010 women from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary acrylamide intake in the full EPIC cohort was estimated using the most recent European acrylamide-content food databases, country-specific food intake questionnaires, and 24-hour dietary recalls at baseline. Multivariate Cox Proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for questionnaire-based acrylamide intake and EC or EOC risk. Cohort analyses were conducted in all women and in subgroups. Two nested case-control studies of acrylamide biomarkers and EC or EOC risk were conducted in non-smoking postmenopausal women. Pre-diagnostic biomarkers of acrylamide and its epoxide metabolite, glycidamide, were measured as hemoglobin adducts (HbAA and HbGA, respectively) using HPLC/MS/MS in red blood cells collected at baseline 5-10 years before diagnosis. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% CI for the relation between acrylamide biomarkers (HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA) and EC or EOC risk. The relation between dietary and demographic determinants of biomarker levels of acrylamide and glycidamide were also examined using simple and multiple linear regression analyses in 801 control women. After a mean follow-up of 11 years, there were 1,382 cases of EC and 1,191 cases of EOC in the EPIC cohort. In general, the results of the dietary acrylamide intake analyses showed no associations with EOC and EC, except for a possible association between higher acrylamide intake and type-I EC in women who were non-smokers and non-users of oral contraceptives (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62). The main food group determinants of acrylamide and glycidamide biomarker levels were biscuits, crackers and cakes; and alcohol intake and body mass index were important determinants of the ratio of glycidamide to acrylamide. The nested case-control study of acrylamide and glycidamide biomarker levels and EC (383 cases, 171 type-I, and 385 controls) did not find any support for associations between acrylamide or glycidamide and EC risk. The nested case-control study of acrylamide and glycidamide biomarkers and EOC risk (334 cases and 417 controls) found some evidence for associations with the third quintile of HbGA, and the second and third quintiles of HbAA+HbGA. Participants classified in the fifth quintile of HbGA or HbAA+HbGA showed statistically non-significant higher risks of EOC (ORHbGA.Q5vsQ1: 1.63, 95% CI: 0.92-2.86; P-trend: 0.04, and ORHbAA+HbGGA.Q5vsQ1: 1.60, 95% CI: 0.89-2.87; P-trend: 0.14). In conclusion, results in women from the EPIC cohort did not provide convincing support for the hypothesis that higher acrylamide and glycidamide exposures are associated with higher risk for EC. For EOC, inconsistent results were observed in our study. Additional nested case- control studies with larger sample size in different populations, and pooled analysis of existing studies of the relation between acrylamide and glycidamide biomarkers and EOC risk should be performed.