Cancer Care Ontario, Toronto, Ontario, Canada.
Am J Epidemiol. 2010 Nov 1;172(9):1000-14. doi: 10.1093/aje/kwq245. Epub 2010 Oct 11.
The risk of colorectal cancer associated with smoking is unclear and may be influenced by genetic variation in enzymes that metabolize cigarette carcinogens. The authors examined the colorectal cancer risk associated with smoking and 26 variants in carcinogen metabolism genes in 1,174 colorectal cancer cases and 1,293 population-based controls recruited in Canada by the Ontario Familial Colorectal Cancer Registry from 1997 to 2001. Adjusted odds ratios were calculated by multivariable logistic regression. Smoking for >27 years was associated with a statistically significant increased colorectal cancer risk (adjusted odds ratio (AOR) = 1.25, 95% confidence interval (CI): 1.02, 1.53) in all subjects. Colorectal cancer risk associated with smoking was higher in males for smoking status, duration, and intensity. The CYP1A1-3801-CC (AOR = 0.47, 95% CI: 0.23, 0.94) and CYP2C9-430-CT (AOR = 0.82, 95% CI: 0.68, 0.99) genotypes were associated with decreased risk, and the GSTM1-K173N-CG (AOR = 1.99, 95% CI: 1.21, 3.25) genotype was associated with an increased risk of colorectal cancer. Statistical interactions between smoking and genetic variants were assessed by comparing logistic regression models with and without a multiplicative interaction term. Significant interactions were observed between smoking status and SULT1A1-638 (P = 0.02), NAT2-857 (P = 0.01), and CYP1B1-4390 (P = 0.04) variants and between smoking duration and NAT1-1088 (P = 0.02), SULT1A1-638 (P = 0.04), and NAT1-acetylator (P = 0.03) status. These findings support the hypothesis that prolonged cigarette smoking is associated with increased risk of colorectal cancer and that this risk may be modified by variation in carcinogen metabolism genes.
吸烟与结直肠癌风险的关联尚不清楚，其风险可能受到香烟致癌物代谢酶的遗传变异的影响。作者研究了吸烟与 1997 年至 2001 年期间，加拿大安大略家族结直肠癌登记处通过安大略家族结直肠癌登记处招募的 1174 例结直肠癌病例和 1293 名基于人群的对照者中 26 种致癌物代谢基因变异与结直肠癌风险的关联。通过多变量逻辑回归计算调整后的比值比。所有受试者中，吸烟>27 年与结直肠癌风险显著增加相关（调整后的比值比（AOR）=1.25，95%置信区间（CI）：1.02，1.53）。在男性中，吸烟状态、持续时间和强度与吸烟相关的结直肠癌风险更高。CYP1A1-3801-CC（AOR=0.47，95%CI：0.23，0.94）和 CYP2C9-430-CT（AOR=0.82，95%CI：0.68，0.99）基因型与结直肠癌风险降低相关，而 GSTM1-K173N-CG（AOR=1.99，95%CI：1.21，3.25）基因型与结直肠癌风险增加相关。通过比较有和没有乘法交互项的逻辑回归模型来评估吸烟和遗传变异之间的统计相互作用。在吸烟状态和 SULT1A1-638（P=0.02）、NAT2-857（P=0.01）和 CYP1B1-4390（P=0.04）变异体之间，以及吸烟持续时间和 NAT1-1088（P=0.02）、SULT1A1-638（P=0.04）和 NAT1-乙酰基转移酶（P=0.03）之间观察到显著的相互作用。这些发现支持这样的假设，即长期吸烟与结直肠癌风险增加有关，而这种风险可能受到致癌物代谢基因变异的影响。
