Association between cigarette smoking, <it>APC </it>mutations and the risk of developing sporadic colorectal adenomas and carcinomas
<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 (&l...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2006-03-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/6/71 |
| _version_ | 1829138033394319360 |
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| author | Hagen Per Lothe Inger Breistein Rebecca Skjelbred Camilla F Sæbø Mona Bock Gunter Hansteen Inger-Lise Kure Elin H |
| author_facet | Hagen Per Lothe Inger Breistein Rebecca Skjelbred Camilla F Sæbø Mona Bock Gunter Hansteen Inger-Lise Kure Elin H |
| author_sort | Hagen Per |
| collection | DOAJ |
| description | <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> |
| first_indexed | 2024-12-14T19:08:53Z |
| format | Article |
| id | doaj.art-4e1077573b91453284881f0e2e58cf41 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-14T19:08:53Z |
| publishDate | 2006-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-4e1077573b91453284881f0e2e58cf412022-12-21T22:50:46ZengBMCBMC Cancer1471-24072006-03-01617110.1186/1471-2407-6-71Association between cigarette smoking, <it>APC </it>mutations and the risk of developing sporadic colorectal adenomas and carcinomasHagen PerLothe IngerBreistein RebeccaSkjelbred Camilla FSæbø MonaBock GunterHansteen Inger-LiseKure Elin H<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>http://www.biomedcentral.com/1471-2407/6/71 |
| spellingShingle | Hagen Per Lothe Inger Breistein Rebecca Skjelbred Camilla F Sæbø Mona Bock Gunter Hansteen Inger-Lise Kure Elin H Association between cigarette smoking, <it>APC </it>mutations and the risk of developing sporadic colorectal adenomas and carcinomas BMC Cancer |
| title | Association between cigarette smoking, <it>APC </it>mutations and the risk of developing sporadic colorectal adenomas and carcinomas |
| title_full | Association between cigarette smoking, <it>APC </it>mutations and the risk of developing sporadic colorectal adenomas and carcinomas |
| title_fullStr | Association between cigarette smoking, <it>APC </it>mutations and the risk of developing sporadic colorectal adenomas and carcinomas |
| title_full_unstemmed | Association between cigarette smoking, <it>APC </it>mutations and the risk of developing sporadic colorectal adenomas and carcinomas |
| title_short | Association between cigarette smoking, <it>APC </it>mutations and the risk of developing sporadic colorectal adenomas and carcinomas |
| title_sort | association between cigarette smoking it apc it mutations and the risk of developing sporadic colorectal adenomas and carcinomas |
| url | http://www.biomedcentral.com/1471-2407/6/71 |
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