To the Editors: Cancer of the left and right colon shows different prevalence at varying ages, in high- and low-incidence nations, and in men and in women. Colorectal carcinomas that arise proximal (right) or distal (left) to the splenic flexure exhibit different epidemiologic and clinicopathologic characteristics, reflecting distinct biological features acquired in embryonic or postnatal development and distinct pathways of transformation that produce a differential response to environmental factors (1, 2). On the other hand, the differences in the epidemiology of proximal and distal colorectal carcinomas could derive from different procarcinogenic factors in the ascending colon compared with the descending colon (1). In comparison with distal colorectal cancer, proximal tumors have been found to be statistically significantly different on mucinous content, degree of histologic differentiation, p53 protein expression, and gene mutation (3). Previous studies have reported a migration in the occurrence of colorectal cancer toward a proximal colonic location. In older individuals, the burden of colorectal carcinoma is greatest, and right colorectal carcinoma is the most common site (4). Thus, the proximal migration of colorectal carcinoma over time may not be attributed to a true increase in the incidence of right colorectal carcinoma but to a decrease in the incidence of distal colorectal carcinoma coupled with the aging of the population (4). All these factors are important in understanding the “shift of tumors from more distal to more proximal sites in the colon” and in evaluating potential strategies for instituting advances in diagnosis and prevention.
More recently, Schoenfeld et al. (5) have observed that among men and women who were matched for a negative fecal occult-blood test and the absence of a family history of colorectal cancer, the diagnostic yield of flexible sigmoidoscopy was significantly higher in men (P ≤ 0.001). The same Authors have suggested that, considered the lower diagnostic yield of flexible sigmoidoscopy among women, “there is a right-sided shift for advanced neoplasia in women as compared with men.”
It has been reported that colorectal carcinomas that arise proximal (right) or distal (left) to the splenic flexure exhibit differences in incidence according to geographic region, age, and gender: proximal tumors would occur predominantly in females, in older individuals, and in low-incidence areas, and distal ones would occur predominantly in younger males from high-incidence areas (2). However, diet, physical activity, smoking, migration from low-risk to high-risk areas, cholecystectomy, chemopreventive agents, and reproductive and hormonal status “per se” could potentially favor the development of right- or left-sided colon tumors (2). Based on the recent technical advances in the molecular characterization of solid tumors, we think that a detailed molecular profiling of colorectal carcinoma would be more reliable. Glebov et al. applied cDNA microarray technology to explore the possibility that mucosal epithelium from adult proximal and distal colon can be distinguished by their pattern of gene expression (1). They showed that, with almost complete concordance, biopsies of adult colonic epithelium can be correctly classified as proximal or distal by gene expression profile.
For this reason, molecular-based classification systems for colorectal carcinoma relying upon distinctive gene expression patterns (1) may allow a better discrimination of subgroups than that provided by tumor location alone.
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