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Cigarette smoking and colorectal cancer: APC mutations, hMLH1 expression, and GSTM1 and GSTT1 polymorphisms

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Author: Lüchtenborg, M. · Weijenberg, M.P. · Kampman, E. · Muijen, G.N. van · Roemen, G.M.J.M. · Zeegers, M.P.A. · Goldbohm, R.A. · Veer, P. van't · Goeij, A.F.P.M. de · Brandt, P.A. van den
Institution: TNO Kwaliteit van Leven
Source:American Journal of Epidemiology, 9, 161, 806-815
Identifier: 238446
doi: doi:10.1093/aje/kwi114
Keywords: Food and Chemical Risk Analysis · Adenomatous polyposis coli · Colorectal neoplasms · Glutathione transferase · Neoplasm proteins · Polymorphism, genetic · Smoking · APC protein · glutathione transferase · glutathione transferase M1 · glutathione transferase T1 · protein MLH1 · unclassified drug · cancer · adult · aged · article · cancer incidence · cancer risk · cigarette smoking · colon polyposis · colorectal cancer · controlled study · female · gene expression · gene mutation · genetic polymorphism · genotype · human · major clinical study · male · Netherlands · polymerase chain reaction · risk assessment · smoking habit · Adenomatous Polyposis Coli · Aged · Carrier Proteins · Colorectal Neoplasms · Confidence Intervals · Diet · Female · Glutathione Transferase · Humans · Incidence · Male · Middle Aged · Neoplasm Proteins · Netherlands · Nuclear Proteins · Polymorphism, Genetic · Prospective Studies · Smoking


The 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. Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. Chemicals / CAS: glutathione transferase, 50812-37-8; protein MLH1, 155577-96-1; Carrier Proteins; Glutathione Transferase, EC; MLH1 protein, human; Neoplasm Proteins; Nuclear Proteins