Hogervorst Janneke G F, Schouten Leo J, Konings Erik J M, Goldbohm R Alexandra, van den Brandt Piet A
Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 Maastricht, the Netherlands.
J Natl Cancer Inst. 2009 May 6;101(9):651-62. doi: 10.1093/jnci/djp077. Epub 2009 Apr 28.
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.
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.
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).
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.
丙烯酰胺是一种可能的人类致癌物，存在于多种热处理食品中。在流行病学研究中，已观察到膳食丙烯酰胺摄入量与子宫内膜癌、卵巢癌、雌激素受体阳性乳腺癌及肾细胞癌风险之间存在正相关。膳食丙烯酰胺摄入量与肺癌风险之间的关联尚不清楚。
我们在荷兰饮食与癌症队列研究中，对58279名男性和62573名女性（年龄55 - 69岁）进行了一项病例队列研究。1986年基线时，通过一份自填问卷评估含丙烯酰胺食物的摄入量及癌症风险因素，并结合荷兰相关食物中的丙烯酰胺水平，以评估膳食丙烯酰胺总摄入量。通过从整个队列中在基线时选取的随机样本（n = 5000）来估计风险人年数。通过与荷兰癌症登记处和荷兰病理登记处的计算机化记录链接，在整个队列中检测新发肺癌病例。使用Cox比例风险模型估计与丙烯酰胺摄入量相关的肺癌风险的风险比和95%置信区间（CI），该模型控制了吸烟（状态、数量和持续时间）及其他肺癌风险因素。所有统计检验均为双侧检验。
经过13.3年的随访（1986年9月17日至2000年1月1日），排除基线时患有其他癌症（非皮肤癌）的病例后，有2649例经组织学证实的原发性肺癌病例（国际肿瘤学疾病分类 - 3代码：C34）。丙烯酰胺摄入量每增加10μg/d，男性肺癌的多变量调整风险比为1.03（95% CI = 0.96至1.11），女性为0.82（95% CI = 0.69至0.96）。丙烯酰胺摄入量最高五分位数（男性中位数摄入量[μg/d] = 37.6，女性 = 36.8）与最低五分位数（男性中位数摄入量[μg/d] = 10.8，女性 = 9.5）相比，男性肺癌风险比为1.03（95% CI = 0.77至1.39，P趋势 = 0.85），女性为0.45（95% CI = 0.27至0.76，P趋势 = 0.01）。女性中腺癌的这种负相关最强（摄入量最高三分位数与最低三分位数相比的风险比 = 0.40，95% CI = 0.21至0.78；P趋势 = 0.01）。
丙烯酰胺摄入量与男性肺癌风险无关，但与女性肺癌风险呈负相关，对腺癌的相关性最强。这一发现表明，丙烯酰胺通过非基因毒性途径参与人类致癌过程。
