Each year, 51,200 people in the US are diagnosed with bladder cancer and 10,600 die of the disease. In addition to tumor invasiveness, metastatic state and nuclear grade, somatic alterations in tumor suppressor genes have been proposed as useful prognostic indicators in the treatment of bladder cancers. Studies are largely limited to clinical series, however, which may over-represent advanced lesions. Furthermore, polymorphisms in DNA repair genes may affect bladder cancer susceptibility and prognosis by compromising the normal repair of DNA lesions formed by exposure to DNA damaging agents. The overall goal of this research project is to investigate tumor markers, genetic factors, and environmental exposures that affect bladder cancer incidence and prognosis using data and samples collected through a large, population-based study of bladder cancer in New Hampshire. Specifically, the study will (1) examine whether DNA repair haplotype modifies bladder cancer incidence, (2) assess overall bladder cancer recurrence or survival rates by tumor stage / grade, and (3) evaluate the prognostic significance of a) constitutional genetic variation in the DNA repair pathway, b) environmental exposures such as smoking and arsenic, and c) the somatic markers: p53 expression and loss of heterozygosity (LOH) of chromosome 9q. This mentored molecular epidemiology research experience under the guidance of the epidemiologist, Dr. Margaret Karagas, (Principal Investigator of the parent case - control study) and molecular biologist, Dr. Joshua Hamilton is part of a training proposal that integrates formal coursework at Dartmouth Medical School. The Research Career Award will give Dr. Angeline Andrew the opportunity to develop her career in the clinical and molecular epidemiology of cancer, and integrate her background in molecular biology with new clinical epidemiology skills, enabling her to establish an independent translational research program. Building on an established investigation of her research mentors, Dr. Andrew's study of prognostic indicators will enable more accurate assessment of a tumor's aggressiveness, guide appropriate treatment options, and ultimately aid the reduction of bladder cancer mortality in the US. ? ? ?
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