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Clinical end points for developing pharmaceuticals to manage patients with a sporadic or genetic risk of colorectal cancer.

ABSTRACT: To reduce the morbidity and mortality from colorectal cancer (CRC), current clinical practice focuses on screening for early detection and polypectomy as a form of secondary prevention, complemented with surgical interventions when appropriate. No pharmaceutical agent is currently approved for use in clinical practice for the management of patients at risk for CRC. This article will review earlier attempts to develop pharmaceuticals for use in managing patients with a sporadic or genetic risk of CRC. It will also discuss therapeutic end points under evaluation in current efforts to develop drugs for treating CRC risk factors.

SUBMITTER: Rial NS

PROVIDER: S-EPMC3587976 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Clinical end points for developing pharmaceuticals to manage patients with a sporadic or genetic risk of colorectal cancer.

Rial Nathaniel S NS Zell Jason A JA Cohen Alfred M AM Gerner Eugene W EW

Expert review of gastroenterology & hepatology 20120801 4

To reduce the morbidity and mortality from colorectal cancer (CRC), current clinical practice focuses on screening for early detection and polypectomy as a form of secondary prevention, complemented with surgical interventions when appropriate. No pharmaceutical agent is currently approved for use in clinical practice for the management of patients at risk for CRC. This article will review earlier attempts to develop pharmaceuticals for use in managing patients with a sporadic or genetic risk of ...[more]

PMID: 22928902

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Project description:BackgroundThe 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 (APC) gene has been reported to have a "gatekeeper" function in the colonic mucosa.MethodsTo 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 APC 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 APC gene. Cases and controls were drawn from a homogeneous cohort of Norwegian origin.ResultsThe mutational spectra of the APC 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 APC truncation mutation status, an association was detected in adenomas without APC mutation in relation to "ever smoking", with an OR = 3.97 (1.26-12.51). For CRC cases without APC mutation "duration of smoking > 30 years", yielded a statistically significant OR = 4.06 (1.20-13.7). The smoking parameter "starting smoking > or = 40 years ago" was only associated with CRC cases with APC 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).ConclusionOur data suggest an association between smoking and adenoma and CRC development. This association was strongest for cases without APC truncation mutation. This may implicate other factors in development of these tumors. The association detected between smoking and CRC cases with APC mutation was in relationship to the smoking parameter "starting smoking > or = 40 years ago", a time period long enough to proceed CRC initiation.

Dataset Information

Clinical end points for developing pharmaceuticals to manage patients with a sporadic or genetic risk of colorectal cancer.

Publications

Clinical end points for developing pharmaceuticals to manage patients with a sporadic or genetic risk of colorectal cancer.

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