Cotterchio Michelle, Boucher Beatrice A, Manno Michael, Gallinger Steven, Okey Allan B, Harper Patricia A
Population Studies and Surveillance, Cancer Care Ontario, 620 University Avenue, Toronto, Ontario, Canada, M5G 2L7.
Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3098-107. doi: 10.1158/1055-9965.EPI-08-0341.
Colorectal cancer literature regarding the interaction between polymorphisms in carcinogen-metabolizing enzymes and red meat intake/doneness is inconsistent. A case-control study was conducted to evaluate the interaction between red meat consumption, doneness, and polymorphisms in carcinogen-metabolizing enzymes. Colorectal cancer cases diagnosed 1997 to 2000, ages 20 to 74 years, were identified through the population-based Ontario Cancer Registry and recruited by the Ontario Family Colorectal Cancer Registry. Controls were sex-matched and age group-matched random sample of Ontario population. Epidemiologic and food questionnaires were completed by 1,095 cases and 1,890 controls; blood was provided by 842 and 1,251, respectively. Multivariate logistic regression was used to obtain adjusted odds ratio (OR) estimates. Increased red meat intake was associated with increased colorectal cancer risk [OR (> 5 versus < or = 2 servings/wk), 1.67 (1.36-2.05)]. Colorectal cancer risk also increased significantly with well-done meat intake [OR (> 2 servings/wk well-done versus < or = 2 servings/wk rare-regular), 1.57 (1.27-1.93)]. We evaluated interactions between genetic variants in 15 enzymes involved in the metabolism of carcinogens in overcooked meat (cytochrome P450, glutathione S-transferase, UDP-glucuronosyltransferases, SULT, NAT, mEH, and AHR). CYP2C9 and NAT2 variants were associated with colorectal cancer risk. Red meat intake was associated with increased colorectal cancer risk regardless of genotypes; however, CYP1B1 combined variant and SULT1A1-638G>A variant significantly modified the association between red meat doneness intake and colorectal cancer risk. In conclusion, well-done red meat intake was associated with an increased risk of colorectal cancer regardless of carcinogen-metabolizing genotype, although our data suggest that persons with CYP1B1 and SULT1A1 variants had the highest colorectal cancer risk.
关于致癌物代谢酶多态性与红肉摄入量/烹饪程度之间相互作用的结直肠癌文献并不一致。开展了一项病例对照研究，以评估红肉消费、烹饪程度与致癌物代谢酶多态性之间的相互作用。通过基于人群的安大略癌症登记处识别出1997年至2000年诊断出的年龄在20至74岁之间的结直肠癌病例，并由安大略家庭结直肠癌登记处招募。对照为安大略省人口中按性别和年龄组匹配的随机样本。1095例病例和1890名对照完成了流行病学和食物问卷；分别有842例病例和1251名对照提供了血液样本。采用多变量逻辑回归来获得调整后的比值比（OR）估计值。红肉摄入量增加与结直肠癌风险增加相关[OR（每周>5份与每周≤2份相比），1.67（1.36 - 2.05）]。熟肉摄入量增加也会使结直肠癌风险显著增加[OR（每周>2份熟肉与每周≤2份生熟适中的肉相比），1.57（1.27 - 1.93）]。我们评估了参与过度烹饪肉类中致癌物代谢的15种酶（细胞色素P450、谷胱甘肽S - 转移酶、尿苷二磷酸葡萄糖醛酸转移酶、磺基转移酶、N - 乙酰基转移酶、微粒体环氧化物水解酶和芳烃受体）的基因变异之间的相互作用。CYP2C9和NAT2变异与结直肠癌风险相关。无论基因型如何，红肉摄入量增加均与结直肠癌风险增加相关；然而，CYP1B1复合变异和SULT1A1 - 638G>A变异显著改变了红肉烹饪程度摄入量与结直肠癌风险之间的关联。总之，无论致癌物代谢基因型如何，熟红肉摄入量增加均与结直肠癌风险增加相关，尽管我们的数据表明携带CYP1B1和SULT1A1变异的人患结直肠癌的风险最高。
