Scientists at deCODE genetics, who made this discovery together with colleagues in Iceland, Sweden and the USA, say that finding this common genetic variant conferring significant risk of a common cancer in the general population is a "milestone in cancer genetics."
About 1 in 5 of men of European ancestry with prostate cancer carry at least one copy of the variant. Men who do carry this gene variant have a 60% higher risk of developing prostate cancer than other men. The gene variant accounts for about 8% of all cases of prostate cancer in men of European ancestry.
The variant confers roughly the same increase in risk among African Americans but is twice as common. As part of the overall project the scientists conducted an African American case-control study, which found that 41% of African American men affected by prostate cancer and 30% of the population are carriers. The variant thus accounts for approximately 16% of prostate cancer among African American men and thereby contributes to the higher incidence of the disease among African Americans than in men of European ancestry.
The discovery of this common gene variant came about through an ongoing genetic study of the entire population of Iceland and was confirmed in groups of men in Sweden and the USA. The findings have been announced in a letter to the online edition of Nature Genetics at www.nature.com/ng, and will appear in the journal's June print edition under the title A common variant associated with prostate cancer in European and African populations.
"This is one of the first genetic variants ever found to confer significant risk of a major cancer among the population in general," Kari Stefansson, CEO of deCODE and senior author on the study said.
"Most previously identified cancer genes have their effect on cancer risk only in families with a clear family history of cancer, or are only found mutated in tumors." Stefanson explained.
"This discovery is important from a medical standpoint because the only firmly established risk factors for the disease until now have been age, family history and ethnicity. As this variant also appears to be associated with the development of more aggressive prostate tumors, a diagnostic test for the variant may enable doctors to make more informed decisions as to how closely they should monitor those who are at high risk, and how aggressively they should treat the disease once it presents. We plan to use this discovery as the basis for the development of such a diagnostic tes."
The variant is located within what deCODE describes as "a putative gene of unknown function" in a region on chromosome 8. Chromosome 8 is one of the most common regions of amplification in cancers of several organs, especially cancers of the breast and prostate. Specifically, the newly discovered variant is allele-8 of the microsatellite DG8S737 on chromosome 8q24.
The total number of patient and control samples analyzed in the study was 3430 and 2675, respectively. Study groups were drawn from the Icelandic Cancer Registry; CAPS1, a population-based study of prostate cancer patients in Sweden; the Prostate Cancer Specialized Program of Research Excellence (SPORE) at Northwestern University; and the Flint Men's Health Study and the Prostate Cancer Genetics Project, both of the University of Michigan.
Prostate cancer
Prostate cancer is the most common non-cutaneous cancer
in men in the industrial world, and is responsible for
more deaths among men than any other cancer except lung
cancer. Prostate cancer develops most frequently in
those over fifty. However many men who develop prostate
cancer never have symptoms, undergo no therapy, and
eventually die of other causes. Whether and how to treat
localized prostate cancer is thus a difficult decision,
and depends largely upon an appraisal of the aggressiveness
of the tumor and the likelihood that the cancer will
spread to other organs.
