GENETIC EPIDEMIOLOGY AND MOLECULAR PATHOLOGY OF COLORECTAL CANCER IN HISPANICS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our overall goal is to develop a paradigm for the prevention, diagnosis, and treatment of colorectal cancer among Hispanics. This pilot study represents the first step to explore the pathways involved in the carcinogenesis of colorectal cancer among Hispanics and will lay the foundation for future investigations into the pathogenesis, molecular biology, and genetic epidemiology relevant to Hispanics with colorectal cancer. The epidemiology and molecular genetics of colorectal neoplasia are well understood, and international population differences are known to occur. Colorectal cancer is the second most common cause of cancer deaths in the United States. In Puerto Rico, colorectal cancer is the second most common cause of cancer affecting approximately 1,500 individuals annually, which represents 12% of all cancer cases in the island. There has been a paucity of reports in the literature regarding colorectal cancer in Puerto Rico. Thus, little is known about the genetic profile and the genetic epidemiology of colorectal cancer in Puerto Rican patients. This proposal will investigate some of the most common genetic changes reported in colorectal cancer to assess their frequency in Hispanic patients. The following specific aims will be pursued: (1) To determine the genetic epidemiology of Puerto Rican Hispanic colorectal cancer patients with regards to demographic and clinicopathologic features for patients treated at the UPRCC; (2) To determine the prevalence of microsatellite instability, determined by automated analysis of shifts in dinucleotide and mononucleotide repeat sequences, for Puerto Rican Hispanic colorectal cancer patients treated at UPRCC; (3) To determine the prevalence of mismatch repair genes' protein expression (hMSH2, hMLH1, hMSH6, hPMS2), determined by immunohistochemisty, and hMLH1 promoter methylation for Puerto Rican Hispanic colorectal cancer patients treated at UPRCC. Understanding the underlying colorectal cancer molecular alterations in Hispanics may perhaps facilitate the development of new strategies for prevention, detection, and treatment that could ultimately decrease the burden of this disease. This pilot investigation will give us preliminary data about the genetic epidemiology of CRC in Puerto Rican Hispanics in a well-characterized cohort of patients, which will be the foundation for future investigations and proposals to secure extramural funding.