Colorectal polyps: the scope and management of the problem.
ABSTRACT Colorectal cancer affects over 150,000 individuals yearly, and accounts for over 50,000 deaths. Much of the benefit of colorectal cancer screening has been attributed to detection and removal of adenomatous polyps, highlighting the importance of colorectal polyps as targets for intervention and as biomarkers for colorectal cancer risk. This review details the epidemiology of sporadic colorectal polyps, rationale behind use of polyps as an important surrogate for colorectal cancer risk, the benefits and limitations of secondary prevention of colorectal polyps through chemopreventive and dietary interventions, as well as colon surveillance.
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ABSTRACT: Cancer is the second leading cause for mortality in US only after heart disease and lacks a good or effective therapeutic paradigm. Despite the emergence of new, targeted agents and the use of various therapeutic combinations, none of the treatment options available is curative in patients with advanced cancer. A growing body of evidence is supporting the idea that human cancers can be considered as a stem cell disease. Malignancies are believed to originate from a fraction of cancer cells that show self renewal and pluripotency and are capable of initiating and sustaining tumor growth. The cancer-initiating cells or cancer stem cells were originally identified in hematological malignancies but is now being recognized in several solid tumors. The hypothesis of stem cell-driven tumorigenesis raises questions as to whether the current treatments, most of which require rapidly dividing cells are able to efficiently target these slow cycling tumorigenic cells. Recent characterization of cancer stem cells should lead to the identification of key signaling pathways that may make cancer stem cells vulnerable to therapeutic interventions that target drug-effluxing capabilities, anti-apoptotic mechanisms, and induction of differentiation. Dietary phytochemicals possess anti-cancer properties and represent a promising approach for the prevention and treatment of many cancers.Mini Reviews in Medicinal Chemistry 04/2010; 10(5):359-71. · 3.19 Impact Factor
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ABSTRACT: Colorectal tumorigenesis is one of the best known processes of cellular transformation in humans. Its characterization has moved ahead by leaps and bounds during the last three decades thanks to major advances in the fields of endoscopy, histology and molecular pathology. And as often happens when a human disease is subjected to in-depth investigation, what originally appeared to be a single entity turns out to include several distinct clinical, histologic, and molecular phenotypes. Among other things, tumor phenotypes can tell us a great deal about the route taken by the tumor cells on their journey toward malignancy. Not surprisingly, some tumors develop along pathways that are “heavily trafficked” (and for this reason, relatively well known); others follow the “roads less traveled.” But if obstacles arise along the way, tumor cells are adept at exploiting alternative routes that permit them to continue their journey toward cancer, and these deviations can give rise to mixed phenotypes. These phenotypes are nonetheless consistent with the concept of carcinogenesis as a nonrandom – and therefore, predictable – process. Each pathway, each crossroads is the result of a specific set of genetic or epigenetic alterations. Many are already well defined, others are only partially characterized, and some are still in the realm of hypothesis. Thus far, we have fairly reliable maps of at least two of the major pathways to colorectal cancer, but with increasingly sophisticated molecular analysis of preinvasive lesions, there is little doubt that we will eventually identify variants of these pathways and uncover others whose existence was not even suspected.12/2010: pages 369-394;
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ABSTRACT: Obesity is a known risk factor for colon cancer and higher body mass index (BMI) has been associated with colorectal adenomas, which are precursor lesions to most colorectal cancers. Polymorphisms in the fat-mass and obesity-associated (FTO) gene have been associated with BMI and larger effects in older versus younger children have been reported. However, no studies have examined associations between FTO polymorphisms, BMI throughout adulthood and colorectal adenomas. Therefore, we evaluated associations between FTO polymorphisms (rs1421085, rs17817449, rs8050136, rs9939609, rs8044769), adult BMI (at recruitment, 50s, 40s, 30s, 20s age decades) and colorectal adenomas in 759 Caucasians and 469 African-Americans. We found that the highest versus the lowest BMI tertile at recruitment [odds ratio (OR) = 1.82; 95% confidence interval (CI): 1.07-2.16] and in the 30s (OR = 1.50; 95% CI: 1.04-2.15) was associated with higher adenoma risk. Stratification by ethnicity revealed that these associations only remained significant in Caucasians. We found that, in Caucasians, having two versus no copies of the variant allele in rs17817449, rs8050136 and rs9939609, which are all in strong linkage disequilibrium, was associated with higher BMI in the 30s and 40s but none of the polymorphisms were associated with adenomas. In African-Americans, having one or two copies of the variant in rs17817449 (OR = 0.61; 95% CI: 0.39-0.95) and rs8050136 (OR = 0.59; 95% CI: 0.38-0.93) was associated with colorectal adenomas and, having two variant copies in rs17817449 and rs8050136 was associated with higher BMI at recruitment and in the 40s, respectively. Our results are consistent with prior studies and show for the first time that FTO polymorphisms are associated with colorectal adenomas in African-Americans.Carcinogenesis 02/2011; 32(5):748-56. DOI:10.1093/carcin/bgr026 · 5.27 Impact Factor