Journal Article

Cigarette smoking and genetic alterations in sporadic colon carcinomas

Brenda Diergaarde, Alina Vrieling, Annemieke A. van Kraats, Goos N.P. van Muijen, Frans J. Kok and Ellen Kampman

in Carcinogenesis

Volume 24, issue 3, pages 565-571
Published in print March 2003 | ISSN: 0143-3334
Published online March 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/24.3.565
Cigarette smoking and genetic alterations in sporadic colon carcinomas

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Cigarette smoking has been inconsistently associated with colon cancer risk. To evaluate the hypothesis that smoking is primarily linked to a specific colon tumor subgroup(s), we assessed associations between smoking and the occurrence of mutations in the APC, K-ras and p53 genes, p53 overexpression, and microsatellite instability (MSI) in a Dutch population-based case–control study on sporadic colon carcinomas. The study population consisted of 176 cases and 249 controls. Smoking status (never, ever), number of cigarettes smoked per day (never, <15, ≥15), total years of smoking (never, ≤30, >30), and years since first started smoking (never, ≤35, >35) were all evaluated. Cigarette smoking status was significantly differently related to p53 overexpression-positive (p53pos) tumors compared with p53 overexpression-negative (p53neg) tumors (p53pos versus p53neg, OR 0.4, 95% CI 0.2–0.9), as well as to tumors with transversion mutations in APC, K-ras or p53 (transv+) compared with tumors without transversion mutations in one of these genes (transv) (transv+ versus transv, OR 2.5, 95% CI 1.0–5.9). Positive associations were observed with p53neg tumors and transv+ tumors when compared with the population-based controls (ever versus transv, OR 1.5, 95% CI 0.9–2.8 and OR 2.2, 95% CI 0.9–5.6, respectively), inverse associations with p53pos tumors and transv tumors (ever versus never, OR 0.5, 95% CI 0.3–1.0 and OR 0.8, 95% CI 0.5–1.3, respectively). Similar patterns of association were observed for the other smoking variables evaluated. In addition, although statistically non-significant, smoking was more notably positively associated with tumors that exhibit K-ras mutations, especially K-ras transversion mutations, than with tumors without K-ras mutations. An inverse relationship between smoking and the occurrence of APC mutations was suggested, whereas no clear associations were observed with MSI. Our data suggest that smoking-related colon cancers develop through a p53neg pathway and that smoking particularly results in colon carcinomas with transversion mutations.

Keywords: APC, adenomatous polyposis col; CI, confidence interval; MCR, mutation cluster region; MSI, microsatellite instability; OR, odds ratio; p53neg, p53 overexpression-negative; p53pos, p53 overexpression-positive; SSCP, single-strand conformation polymorphism.

Journal Article.  6538 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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