Multiple genes may affect age at onset of hereditary prostate cancer

Multiple genes may affect patients’ age at the onset of hereditary prostate cancer.

In the July 10th issue of the International Journal of Cancer, a multicenter team headed by Dr. Ellen M. Wijsman at the University of Seattle, Washington describes a study of 3796 men in 263 families with multiple cases of prostate cancer. The families were participants in the Prostate Cancer Genetic Research Study. The authors used Markov chain Monte Carlo oligogenic segregation analysis to estimate the number of quantitative trait loci and their contribution to the variance in age at the diagnosis of hereditary prostate cancer. They also investigated the mode of inheritance of each quantitative trait locus.According to their report, two to three genes contribute to variance in age at onset. The two largest quantitative trait loci, which together contribute approximately 90% to the total variance, “are both effectively dominant,” the researchers report.The largest quantitative trait locus accounted for 77% of the variance. “The shift in age at onset for the high-risk genotypes for the largest…locus is almost twice that for the next largest,” the authors note. They found, for example, that the mean age of onset in men homozygous for the high-risk allele of the largest locus was approximately 40 years of age, while the mean age at onset for men homozygous for the low-risk allele was approximately 90 years of age.The authors also analyzed the effects of two covariates. Because primary neuroepithelial brain cancer is associated with prostate cancer, they estimated the effect of the presence or absence of at least one blood relative with primary neuroepithelial brain cancer. In addition, they estimated the effect of a diagnosis of prostate cancer before and after 1988, when the prostate-specific antigen test became available. The presence or absence of brain cancer in a relative did not make a significant contribution to the variance of age at onset. The availability of prostate-specific antigen testing, however, did make an important contribution.Their findings, the investigators write, suggest “that single-locus models used for localizing genes for hereditary prostate cancer may…be inefficient, and may explain the difficulty of confirmation in linkage studies based on single-locus models.”They point out, however, that they were studying variance in age at onset, and not risk of disease. “Our results,” they conclude, “are instructive for further mapping studies and show the need for complex analysis methods, which can incorporate multiple trait loci, to localize genes for hereditary prostate cancer.”(Source: Int J Cancer 2003;105:630-635: Reuters Health: July 11, 2003: Oncolink)