Slattery M L, Potter J D, Samowitz W, Bigler J, Caan B, Leppert M
University of Utah School of Medicine, Salt Lake City 84108, USA.
Cancer Epidemiol Biomarkers Prev. 1998 Dec;7(12):1079-84.
Cigarette smoking has been associated inconsistently with colon cancer. The extent to which genetic profile influences susceptibility to the inducement of colon cancer by cigarette smoking is not known. In this study, we evaluated the associations between smoking cigarettes and polymorphisms of the NAT2 and GSTM-1 genes using data obtained from an incident case-control study of 1993 cases of colon cancer and 2410 age- and sex- matched controls. Neither NAT2 nor GSTM-1 polymorphisms were significantly associated with colon cancer, except among older women, in whom the intermediate/rapid imputed phenotype was associated with increased risk of colon cancer [odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.0-1.81. Using several indicators of cigarette smoking, we observed no significant interaction between these genotypes and cigarette smoking and colon cancer. The major variation in association with colon cancer was from the amount of cigarette exposure, with those smoking a pack or more of cigarettes per day being at an approximately 40% increased risk of colon cancer; this association did not vary by genotype. However, those who stopped smoking 5-14 years prior to diagnosis and who where intermediate/rapid acetylators were at a slightly greater risk than those who were slow acetylators (for men, OR = 1.6, 95% CI = 1.0-2.4; for women, OR = 2.5, 95% CI = 1.4-4.4). Associations were similar when proximal and distal tumors were examined and separated for age at the time of diagnosis. The lack of an association does not rule out the possibility of other genetic polymorphisms interacting with cigarette smoke to cause colon cancer, nor does it take into account individual phenotypic variability.
吸烟与结肠癌的关联并不一致。基因谱在多大程度上影响吸烟诱发结肠癌的易感性尚不清楚。在本研究中，我们利用1993例结肠癌病例及2410例年龄和性别匹配的对照的发病病例对照研究数据，评估了吸烟与NAT2和GSTM-1基因多态性之间的关联。除老年女性外，NAT2和GSTM-1基因多态性均与结肠癌无显著关联，在老年女性中，中间/快速推断表型与结肠癌风险增加相关[比值比(OR)=1.4，95%置信区间(CI)=1.0-1.8]。使用几种吸烟指标，我们未观察到这些基因型与吸烟及结肠癌之间存在显著的相互作用。与结肠癌相关的主要差异来自吸烟暴露量，每天吸烟一包或更多的人患结肠癌的风险增加约40%；这种关联不因基因型而异。然而，在诊断前5-14年戒烟且为中间/快速乙酰化者的风险略高于慢乙酰化者(男性，OR=1.6，95%CI=1.0-2.4；女性，OR=2.5，95%CI=1.4-4.4)。在检查近端和远端肿瘤并按诊断时的年龄分开时，关联相似。缺乏关联并不排除其他基因多态性与香烟烟雾相互作用导致结肠癌的可能性，也未考虑个体表型变异性。
