Journal Article

Cigarette Smoking and Colorectal Cancer: <i>APC</i> Mutations, hMLH1 Expression, and <i>GSTM1</i> and <i>GSTT1</i> Polymorphisms

Margreet Lüchtenborg, Matty P. Weijenberg, Ellen Kampman, Goos N. van Muijen, Guido M. J. M. Roemen, Maurice P. A. Zeegers, R. Alexandra Goldbohm, Pieter van 't Veer, Anton F. P. M. de Goeij and Piet A. van den Brandt

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 161, issue 9, pages 806-815
Published in print May 2005 | ISSN: 0002-9262
Published online May 2005 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/kwi114
Cigarette Smoking and Colorectal Cancer: APC Mutations, hMLH1 Expression, and GSTM1 and GSTT1 Polymorphisms

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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.

Keywords: adenomatous polyposis coli; colorectal neoplasms; glutathione transferase; neoplasm proteins; polymorphism, genetic; smoking; APC, adenomatous polyposis coli; CI, confidence interval; GSTM1, glutathione S-transferase M1; GSTT1, glutathione S-transferase T1; hMLH1, human mut-L homologue 1; IRR, incidence rate ratio; PALGA, Pathologisch Anatomisch Landelijk Geautomatiseerd Archief; PCR, polymerase chain reaction

Journal Article.  5707 words.  Illustrated.

Subjects: Public Health and Epidemiology

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