Variation in Gene Increases Prostate Cancer Risk

This gene variation was discovered on chromosome 8. Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 8, one inherited from each parent, form one of the pairs. Chromosome 8 spans about 146 million base pairs (the chemicals that comprise DNA), and represents about 5% of the total DNA in cells, containing an estimated 700 to 1,100 genes.

The research was conducted by investigators from the U.S. National Cancer Institute (NCI; Bethesda, MD, USA), part of the U.S. National Institutes of Health (NIH; Bethesda, MD, USA), and their partners in the Cancer Genetic Markers of Susceptibility (CGEMS; Bethesda, MD, USA) initiative. CGEMS researchers are scanning the entire human genome to identify common, inherited gene mutations that increase the risks for breast and prostate cancers. The results appear in the May 1, 2007, issue of the journal Nature Genetics.

Discovery of this common variation is very exciting. Building on this finding we may be able to identify men at highest risk for prostate cancer, diagnose the disease earlier, and hopefully prevent it all together. One of the next steps is to understand the mechanism by which this genetic variation exerts its effect on cancer risk, said NCI director John E. Niederhuber, M.D.

The region the CGEMS study identified on chromosome 8 is marked by a number of single nucleotide polymorphisms (SNPs), including rs6983267. SNPs are the most common type of gene variant in which a single unit of DNA may vary from one person to the next. The rs6983267 SNP is located in a segment of DNA that has few known or predicted genes for prostate cancer.

The researchers also confirmed that a previous finding of a different variant, marked by SNP rs1447295, is also associated with prostate cancer. The rs1447295 SNP is located nearby on the same arm of chromosome 8. The old and the new susceptibility loci, or gene locations, appear to act independently; a change in one region did not affect the degree of risk conferred by the other. We now have two significant regions in the same general area that convey risk for prostate cancer. This will undoubtedly focus multidisciplinary studies on this stretch of DNA, called 8q24, said Meredith Yeager, Ph.D., lead author of the study.

The rs1447295 location could be responsible for about 7% of prostate cancer cases in white men of northern European descent. Thus, taken together with rs6983267, these two genetic changes could account for as much as one quarter of prostate cancer cases in white men. The increased risk conferred by these loci was observed for all age groups studied.

CGEMS allows us to look systematically across the entire human genome and search for common genetic variations that confer risk for prostate cancer, a very common and very complex disease said Stephen Chanock, M.D., director of NCI's Core Genotyping Facility in the Advanced Technology Center.

Identification of new regions like 8q24 furthers efforts to uncover the genetic basis of prostate cancer, which may eventually lead to more insights into cancer causation in general, added Gilles Thomas, M.D., Ph.D., lead scientist of CGEMS.

An initial genome-wide association study was conducted in 2,329 men from across the United States who are participating in the NCI's Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) that began in 1993. The PLCO analysis compared 1,172 men with prostate cancer to 1,157 who did not have cancer.


Related Links:
National Institutes of Health
National Cancer Institute
Cancer Genetic Markers of Susceptibility