Journal of the National Cancer Institute Advance Access originally published online on April 28, 2009
JNCI Journal of the National Cancer Institute 2009 101(9):651-662; doi:10.1093/jnci/djp077
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© The Author 2009. Published by Oxford University Press.
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Lung Cancer Risk in Relation to Dietary Acrylamide Intake
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: jgf.hogervorst{at}epid.unimaas.nl).
Background: 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 person-years 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 multivariable-adjusted 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.
| 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. Contribution This study suggested that acrylamide intake does not increase the risk of lung cancer. The decreased risk of lung cancer with increasing intake of acrylamide in women observed in this study and previous studies on hormonal effects of acrylamide in animals raise the possibility that acrylamide may be involved in carcinogenesis via nongenotoxic effects. 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
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Manuscript received August 25, 2008; revised February 13, 2009; accepted March 5, 2009.
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J Natl Cancer Inst 2009 101: 613.
J Natl Cancer Inst 2009 101: 613.
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