Null Results in Brief Dietary Acrylamide Intake and Brain Cancer Risk Janneke G.F. Hogervorst, 1 Leo J. Schouten, 1 Erik J.M. Konings, 2 R. Alexandra Goldbohm, 3 and Piet A. van den Brandt 1 1 Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands; 2 Food and Consumer Product Safety Authority, Department of Research and Development, Eindhoven, the Netherlands; and 3 Department of Prevention and Health, TNO Quality of Life, Leiden, the Netherlands Abstract Background: Acrylamide is a probable human carcino- gen, which is present in several heat-treated foods. In epidemiologic studies, positive associations with en- dometrial, ovarian, and renal cell cancer risk have been observed. The incidence of central nervous system tumors was increased upon acrylamide administration in drinking water to rats. In the current study, the association between dietary acrylamide intake and human brain cancer risk was investigated for the first time. Methods: In 1986, 120,852 persons (ages 55-69 years) were included in the Netherlands Cohort Study on diet and cancer. At baseline, a random subcohort of 5,000 participants was randomly selected from the total cohort for a case-cohort approach. Acrylamide intake was assessed with a food frequency questionnaire at baseline and based on acrylamide analyses in relevant Dutch foods. Hazard ratios (HR) were calculated using Cox proportional hazards analysis. Subgroup analyses were done for microscopically verified brain cancer, astrocytic gliomas, high-grade astrocytic gliomas, and never-smokers. The acrylamide risk estimates were adjusted for possible brain cancer risk factors. Results: After 16.3 years of follow-up, 216 brain cancer cases were available for analysis. The multivariable- adjusted HR per 10 Mg/d increment of acrylamide intake was 1.02 (95% confidence interval, 0.89-1.16). HRs were not significantly increased either when dietary acrylamide intake was analyzed as a categorical variable. Also, there was no association in the sub- groups based on histology and smoking. Conclusion: Inthisprospectivecohortstudy,acrylamide intake was not associated with brain cancer risk. (CancerEpidemiolBiomarkersPrev2009;18(5):1663–6) Introduction Acrylamide has been classified as a probable human carcinogenbasedonanimalstudies(1),andissince2002 known to be present in several carbohydrate-rich heated foods, such as French fries and potato crisps. Recent epidemiologic studies on dietary acrylamide intake and cancer risk reported positive associations with endometrial, ovarian, and renal cell cancer risk (2, 3). An advisory group of the IARC recently gave high priority to acrylamide for assessment in future IARC Monograph series (4). Because the acrylamide molecule is small and hydro- philic, it passively diffuses throughout the whole body, and for this reason, theoretically all tissues are targets for acrylamide carcinogenesis. The incidence of central nervous system tumors was increased upon acrylamide administration in drinking water in one of the two lifetime carcinogenicity studies with rats (5, 6). In this prospectivecohortstudy,weinvestigatedtheassociation between dietary acrylamide intake and human brain cancer risk. Materials and Methods Study Participants. The study took place within the Netherlands Cohort Study on diet and cancer, which started in September 1986 (7). At baseline, the partic- ipants (58,279 men and 62,573 women aged 55-69 years) completed a self-administered questionnaire on diet and other possible risk factors for cancer. The case-cohort approach was used for data processing and analysis; cases were enumerated for the entire cohort, whereas the accumulated person-time for the total cohort was estimated from a subcohort of 5,000 men and women randomlysampledfromthefullcohortatbaseline.Cases andsubcohortmemberswereexcludedfromtheanalysis if they had been diagnosed with cancer (other than skin cancer) at baseline and if their dietary data were incomplete or inconsistent. Follow-up. Incident cases in the total cohort were detected by record linkage to the Netherlands Cancer Registry. The completeness of cancer follow-up through linkage with these cancer registries was assessed to be at least 96%, whereas the follow-up of the subcohort at the end of the follow-up period was nearly 100% complete. Further details on the design of the study and methods of follow-up are presented elsewhere (7). Cancer Epidemiol Biomarkers Prev 2009;18(5). May 2009 Received11/28/08;revised2/6/09;accepted2/26/09;publishedOnlineFirst4/21/09. Requests for reprints: Janneke Hogervorst, Department of Epidemiology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, the Netherlands. Phone: 31-433-882-391; Fax: 31-433-884-128. E-mail: jgf.hogervorst@epid.unimaas.nl Copyright D 2009 American Association for Cancer Research. doi:10.1158/1055-9965.EPI-08-1133 1663 on July 2, 2020. © 2009 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from