Prostate cancer is the most common solid tumor and the second leading cause of cancer deaths among American men. Despite the high morbidity and mortality associated with the disease, little is known about the risk factors or underlying molecular defects that predispose men to prostate cancer. It is clear, however, that both environmental and genetic factors are implicated in the etiology of this complex disease. Genetic epidemiology studies of prostate cancer are focusing on identification of rare, high-penetrant genes responsible for hereditary prostate cancer and frequent, low-penetrant genes thought to account for a substantial proportion of the prostate cancers in the general population and to be involved in gene-environmental interactions. The proposed study will focus on the latter type of gene, by investigating polymorphism in the GSTPi gene involved in the intracellular detoxification of mutagens, carcinogens, and related metabolites. The investigators hypothesize that allelic variation in the GSTPi gene influences prostate cancer incidence. Specifically, they will test the hypothesis that men who are heterozygous for the GSTPi 1a/1b alleles have a reduced ability to detoxify environmental carcinogens and thereby have an elevated risk of prostate cancer. To address this question the investigators propose a population-based case-control study. Extensive risk factor data, dietary questionnaires and blood samples have been collected from 648 incident, histologically confirmed prostate cancer cases and 571 control men without a history of prostate cancer. Constitutional DNA will be used to genotype cases and controls for polymorphism in the GSTPi gene. Logistic regression models will be used to estimate the relative risk of prostate cancer associated with genotype. They also will examine whether or not the strength of the associations with these polymorphisms differ according to family history of prostate cancer, dietary intake, and occupational exposures. The proposed study may provide clues on specific molecular markers that identify men at elevated risk of prostate cancer, increase our knowledge of the molecular biology of this common disease, and suggest new approaches for prostate cancer prevention.
| Agalliu, Ilir; Langeberg, Wendy J; Lampe, Johanna W et al. (2006) Glutathione S-transferase M1, T1, and P1 polymorphisms and prostate cancer risk in middle-aged men. Prostate 66:146-56 |
