Cigarette Smoking, Genetic Variants in Carcinogen-metabolizing Enzymes, and Colorectal Cancer Risk
Cigarette Smoking, Genetic Variants in Carcinogen-metabolizing Enzymes, and Colorectal Cancer Risk
复制标题
DOI：
10.1093/aje/kwq245
复制
发表时间：
2010-11-01
影响因子：
5
通讯作者：
Harper, Patricia
中科院分区：
文献类型：
--
作者：
Cleary, Sean P.;Cotterchio, Michelle;Harper, Patricia
与吸烟相关的结直肠癌风险尚不清楚，可能受到代谢香烟致癌物的酶的遗传变异的影响。作者在加拿大安大略家族性结直肠癌登记处从1997年至2001年招募的1,174例结直肠癌病例和1,293例以人群为基础的对照中，研究了与吸烟和致癌物代谢基因的26种变异相关的结直肠癌风险。校正后的比值比通过多变量logistic回归计算。在所有受试者中，吸烟> 27年与结直肠癌风险的统计学显著增加相关（校正比值比（AOR）= 1.25，95%置信区间（CI）：1.02，1.53）。在男性中，吸烟状态、持续时间和强度与结直肠癌风险相关。CYP1A1-3801-CC（AOR = 0.47，95% CI：0.23，0.94）和CYP 2C 9 -430-CT（AOR = 0.82，95% CI：0.68，0.99）基因型与风险降低相关，GSTM 1-K173 N-CG基因型与风险降低相关，（AOR = 1.99，95%CI：1.21，3.25）基因型与结直肠癌风险增加相关。吸烟和遗传变异之间的统计学相互作用进行了评估，通过比较逻辑回归模型，有和没有乘法的相互作用项。吸烟状态与SULT 1A 1 -638（P = 0.02）、NAT 2 -857（P = 0.01）和CYP 1B 1 -4390（P = 0.04）变异体之间以及吸烟持续时间与NAT 1 -1088（P = 0.02）、SULT 1A 1 -638（P = 0.04）和NAT 1-乙酰化（P = 0.03）状态之间观察到显著的相互作用。这些发现支持了这一假设，即长期吸烟与结直肠癌风险增加有关，并且这种风险可能会因致癌物代谢基因的变化而改变。
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.