Lung Cancer Risk in Relation to Dietary Acrylamide Intake

ARTICLE Lung Cancer Risk in Relation to Dietary Acrylamide Intake Janneke G. F. Hogervorst, Leo J. Schouten, Erik J. M. Konings, R. Alexandra Goldbohm, Piet A. van den Brandt Acrylamide is a probable human carcinogen that is present in several heat-treated foods. In epidemiological studies, positive associations between dietary acrylamide intake and the risks of endometrial, ovarian, estrogen receptor–positive breast, and renal cell cancers have been observed. The association between dietary acrylamide intake and lung cancer risk is not known. Methods We conducted a case–cohort study among 58 279 men and 62 573 women (aged 55–69 years) in the Netherlands Cohort Study on Diet and Cancer. Intakes of acrylamide-containing foods and risk factors for cancer were assessed with a self-administered questionnaire at baseline in 1986 and combined with acrylamide levels in relevant Dutch foods to assess total dietary acrylamide intake. The number of personyears at risk was estimated by using a random sample of participants from the total cohort that was chosen at baseline (n = 5000). Incident lung cancer cases in the total cohort were detected by computerized record linkages to the Netherlands Cancer Registry and the Netherlands Pathology Registry. Hazard ratios and 95% confidence intervals (CIs) for the risk of lung cancer associated with acrylamide intakes were estimated using Cox proportional hazards models that controlled for smoking (status, quantity, and duration) and other lung cancer risk factors. All statistical tests were two-sided. Results After 13.3 years of follow-up (September 17, 1986 up to January 1, 2000) there were 2649 cases of primary, histologically verified lung cancer (International Classification of Diseases for Oncology-3 code: C34) when cases with prevalent cancer at baseline (other than skin cancer) were excluded. The multivariableadjusted hazard ratio of lung cancer for a 10-µg/d increment of acrylamide intake was 1.03 (95% CI = 0.96 to 1.11) for men and 0.82 (95% CI = 0.69 to 0.96) for women. The hazard ratio of lung cancer for the highest (median intake [µg/d]: men = 37.6 and women = 36.8) vs the lowest (median intake [µg/d]: men = 10.8 and women = 9.5) quintile of acrylamide intake was 1.03 (95% CI = 0.77 to 1.39, Ptrend = .85) for men and 0.45 (95% CI = 0.27 to 0.76, Ptrend = .01) for women. The inverse association in women was strongest for adenocarcinoma (hazard ratio for highest vs lowest tertile of intake = 0.40, 95% CI = 0.21 to 0.78; Ptrend = .01). Conclusions Acrylamide intake was not associated with lung cancer risk in men but was inversely associated in women, most strongly for adenocarcinoma. This finding suggests that acrylamide is involved in human carcinogenesis through pathways other than genotoxicity. J Natl Cancer Inst 2009;101:651–662 Acrylamide was found several years ago to be present in commonly consumed carbohydrate-rich heated foods (1) such as French fries and potato crisps and is classified as a probable human carcinogen based on results from animal studies (2). Recently, an advisory group of the International Agency for Research on Cancer (IARC) gave high priority to assessment of acrylamide as a human carcinogen in future IARC Monograph series (3), probably because of the outcomes of some recent epidemiological studies on acrylamide and cancer risk (4–6). Animal studies have shown positive dose–response relationships between acrylamide exposure and cancer in multiple organs and tissues (7–10), including oral tissues, thyroid gland, and mammary gland, in the rat and lung and skin in the mouse. Recently, two prospective epidemiological studies have shown positive associations between acrylamide exposure and cancer risk. In one of those studies, we observed that increased dietary acrylamide exposure was jnci.oxfordjournals.org positively associated with the risk of postmenopausal endometrial and ovarian cancers (but not with the risk of postmenopausal Affiliations of authors: Department of Epidemiology, GROW–School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands (JGFH, LJS, PAvdB); Food and Consumer Product Safety Authority, Region South, Department of Research & Development, Eindhoven, the Netherlands (EJMK); Department of Prevention and Health, Netherlands Organisation for Applied Scientific Research, Quality of Life, Leiden, the Netherlands (RAG). Correspondence to: Janneke G. F. Hogervorst, MSc, Department of Epidemiology, GROW–School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands (e-mail: ). See “Funding” and “Notes” following “References.” DOI: 10.1093/jnci/djp077 © The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: . JNCI | Articles 651 Background CONTEXT AND CAVEATS Prior knowledge Acrylamide, which is found in commonly consumed foods, had been shown to be a carcinogen in animal studies. Study design Prospective case–cohort study with cancer incidence determined from data from national registries. Intake of acrylamide-containing foods was estimated based on a self-administered questionnaire and government data on acrylamide content in foods. Cox proportional hazard regression models that adjusted for known or potential risk factors were used to assess the association of acrylamide intake with lung cancer. Implications Additional epidemiological studies on the association of acrylamide intake with cancer at various sites are warranted. Limitations Nondifferential misclassification of exposure may have obscured an association of acrylamide exposure with increased risk of lung cancer. From the Editors breast cancer) (4), as well as with the risk of renal cell cancer (but not with the risk of bladder or prostate cancer) (5). In the other study, a Danish group observed a positive association between acrylamide exposure and postmenopausal estrogen receptor–positive breast cancer risk using acrylamide–hemoglobin adducts for the assessment of acrylamide exposure (6). More prospective epidemiological studies on the association between acrylamide intake and cancer risk are needed, especially for cancer sites that have not yet been studied, such as the lung. Here we report the first prospective epidemiological study to examine the association between dietary acrylamide intake and lung cancer risk. Methods Study Design and Participants This study was conducted within the prospective Netherlands Cohort Study (NLCS) on Diet and Cancer, which started in September 1986 with the inclusion of 58 279 men and 62 573 women aged 55–69 years who were randomly sampled from Dutch municipal registries (11). At baseline, study participants were sent a questionnaire on diet and other risk factors for cancer, such as smoking and physical activity, that was designed to be self-administered. Participants were informed that by returning the completed questionnaire they (...truncated)