Cigarette smoking and colorectal cancer:: APC mutations, hMLH1 expression, and GSTM1 and GSTT1 polymorphisms
Cigarette smoking and colorectal cancer:: APC mutations, hMLH1 expression, and GSTM1 and GSTT1 polymorphisms
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DOI：
10.1093/aje/kwi114
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发表时间：
2005-05-01
影响因子：
5
通讯作者：
van den Brandt, PA
中科院分区：
文献类型：
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作者：
Lüchtenborg, M;Weijenberg, MP;van den Brandt, PA
d 吸烟对散发性结直肠癌的影响可能因肿瘤的分子方面或谷胱甘肽 S-转移酶 M1 (GSTM1) 或谷胱甘肽 S-转移酶 T1 (GSTT1) 基因型而异。在荷兰饮食与癌症前瞻性队列研究中，根据吸烟特征（661 例，2,948 名亚队列成员），计算了 1986-1993 年整体结直肠癌、有或没有腺瘤性息肉病 (APC) 突变的肿瘤以及有或没有人类 mut-L 同源物 1 (hMLH1) 表达的肿瘤的调整后发病率比率。进行仅病例分析以估计吸烟与 GSTM1 和 GSTT1 基因型之间相互作用的比值比。与从不吸烟者相比，高吸烟频率会增加结直肠癌的风险（每天吸烟五支，发病率比 (IRR) = 1.07，95% 置信区间 (CI)：1.03, 1.12），并且这种关联在 371 个没有截短 APC 突变的肿瘤中更为明显（IRR = 1.11，95% CI：1.05, 1.17）。长期吸烟与 56 个肿瘤中 hMLH1 表达缺乏相关（10 年增量，IRR = 1.17，95% CI：1.00，1.37）。未观察到吸烟与 GSTM1 或 GSTT1 基因型之间存在统计学上显着的相互作用。这些结果表明吸烟与结直肠癌的风险相关，这种关联可能取决于 APC 突变和 hMLH1 表达状态所定义的肿瘤分子特征。
dThe contribution of cigarette smoking to sporadic colorectal cancer may differ according to molecular aspects of the tumor or according to glutathione S-transferase M1 (GSTM1) or glutathione S-transferase T1 (GSTT1) genotype. In the prospective Netherlands Cohort Study on Diet and Cancer, adjusted incidence rate ratios for 1986-1993 were computed for overall colorectal cancer, tumors with and without adenomatous polyposis coli (APC) mutations, and tumors with and without human mut-L homologue 1 (hMLH1) expression, according to cigarette smoking characteristics (661 cases, 2,948 subcohort members). Case-only analyses were performed to estimate odds ratios for interaction between cigarette smoking and GSTM1 and GSTT1 genotypes. In comparison with never smokers, a high smoking frequency increased the risk of colorectal cancer (for a five-cigarette/day increment, incidence rate ratio (IRR) = 1.07, 95% confidence interval (CI): 1.03, 1.12), and this association was stronger in 371 tumors without a truncating APC mutation (IRR = 1.11, 95% CI: 1.05, 1.17). Long-term smoking was associated with lack of hMLH1 expression in 56 tumors (for a 10-year increment, IRR = 1.17, 95% CI: 1.00, 1.37). No statistically significant interactions between smoking and GSTM1 or GSTT1 genotype were observed. These results indicate that cigarette smoking is associated with risk of colorectal cancer, and this association may depend on molecular characteristics of the tumor as defined by APC mutation and hMLH1 expression status.