Lung cancer risk in relation to dietary acrylamide intake.
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-microg/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 [microg/d]: men = 37.6 and women = 36.8) vs the lowest (median intake [microg/d]: men = 10.8 and women = 9.5) quintile of acrylamide intake was 1.03 (95% CI = 0.77 to 1.39, P(trend) = .85) for men and 0.45 (95% CI = 0.27 to 0.76, P(trend) = .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; P(trend) = .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.
Hogervorst
Janneke G F
JG
Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 Maastricht, the Netherlands. jgf.hogervorst@epid.unimaas.nl
Schouten
Leo J
LJ
Konings
Erik J M
EJ
Goldbohm
R Alexandra
RA
van den Brandt
Piet A
PA
D020106:Acrylamide / Q000008:administration & dosage* / Q000009:adverse effects*; D000230:Adenocarcinoma / Q000139:chemically induced / Q000453:epidemiology; D000368:Aged; D002273:Carcinogens / Q000008:administration & dosage*; D016022:Case-Control Studies; D004034:Diet Surveys; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D005247:Feeding Behavior; D005260:Female; D005500:Follow-Up Studies; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008498:Medical Record Linkage; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
D002273:Carcinogens; D012739:Gonadal Steroid Hormones; D020106:Acrylamide