| Summary: | <p>Abstract</p> <p>Background</p> <p>The association between colorectal cancer (CRC) and smoking has not been consistent. Incomplete smoking history and association to a specific subset of CRC tumors have been proposed as explanations. The adenomatous polyposis coli (<it>APC</it>) gene has been reported to have a "gatekeeper" function in the colonic mucosa.</p> <p>Methods</p> <p>To evaluate the hypothesis that cigarette smoking is associated with adenoma and carcinoma development and further to investigate whether this association is due to mutations in the <it>APC </it>gene, we used a study population consisting of 133 cases (45 adenomas and 88 carcinomas) and 334 controls. All tumors were sequenced in the mutation cluster region (MCR) of the <it>APC </it>gene. Cases and controls were drawn from a homogeneous cohort of Norwegian origin.</p> <p>Results</p> <p>The mutational spectra of the <it>APC </it>gene revealed no difference in frequencies of mutations in cases based on ever and never smoking status. An overall case-control association was detected for adenomas and "ever smoking" OR = 1.73 (95% CI 0.83–3.58). For CRC cases several smoking parameters for dose and duration were used. We detected an association for all smoking parameters and "duration of smoking > 30 years", yielded a statistically significant OR = 2.86 (1.06–7.7). When cases were divided based on <it>APC </it>truncation mutation status, an association was detected in adenomas without <it>APC </it>mutation in relation to "ever smoking", with an OR = 3.97 (1.26–12.51). For CRC cases without <it>APC </it>mutation "duration of smoking > 30 years", yielded a statistically significant OR = 4.06 (1.20–13.7). The smoking parameter "starting smoking ≥ 40 years ago" was only associated with CRC cases with <it>APC </it>mutations, OR = 2.0 (0.34–11.95). A case-case comparison revealed similar findings for this parameter, OR = 2.24 (0.73–6.86).</p> <p>Conclusion</p> <p>Our data suggest an association between smoking and adenoma and CRC development. This association was strongest for cases without <it>APC </it>truncation mutation. This may implicate other factors in development of these tumors. The association detected between smoking and CRC cases with <it>APC </it>mutation was in relationship to the smoking parameter "starting smoking ≥ 40 years ago", a time period long enough to proceed CRC initiation.</p>
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