For example, Benedix et al. (18) demonstrated that right-sided tumors tended to occur in older women with more co-morbidities. These tumors tended to show a more poorly differentiated histology and there was an overall worse prognosis

in patients with RCC as compared to LCC. Mequid et al. using retrospective survival analysis of data from the Lenvatinib research buy Surveillance, Epidemiology, and End Results Program (SEER) database between 1988 and 2003, showed that RCC had a 5% increased mortality risk relative to LCC (19). The Mequid study treated many of the parameters observed by the Benedix group as confounders, and as such, Inhibitors,research,lifescience,medical more stringently controlled for age, gender, race, tumor stage, tumor size, histologic grade, number of lymph nodes examined, and year of diagnosis. From these two studies, it appears

there is a difference in behavior of RCC and LCC, but it is not precisely clear what the extent of the difference is. Other studies appear to contradict these reports, although they also Inhibitors,research,lifescience,medical have shown differences in morbidity and mortality between patients with right-sided versus left-sided cancers. Weiss et al. also used SEER data to show that there was no Inhibitors,research,lifescience,medical statistically significant difference in mortality between RCC and LCC for all stages combined and for stage I disease. However, there was a significant decrease in mortality seen with stage II RCC as Inhibitors,research,lifescience,medical compared to LCC. This is in

contrast to an increased mortality seen in stage III right-sided cancers when compared to the left colon (17). In addition, this group performed an extensive adjustment of confounding factors as well as limiting the sample to a more homogenous group of patients with a narrow age distribution (66 years and older as a result of Medicare linkage) and those considered for surgery with curative therapy (by excluding AJCC stage IV and those undergoing palliative procedures). While this body of literature implies differences Inhibitors,research,lifescience,medical in tumor biology based on anatomic location, it does not either unambiguously define those differences. More studies are necessary to fully elucidate the phenomenon in question. Molecular basis of colorectal cancer Differences between right- and left-sided colorectal cancers are observed at the molecular level as well as the gross anatomic level. The primary mechanism through which molecular alterations lead to colorectal cancer appears to be genomic instability. Genomic instability may take a number of forms which are generally classified as chromosomal instability, DNA-repair defects, and aberrant DNA methylation (20). Chromosomal instability is the most common type of genomic instability associated with the development of colorectal cancers. These somatic defects are characteristic of roughly 80-85% of sporadic colorectal cancers (20).