Wednesday, July 25, 2012

Confirmed: Mutation Increases Prostate Cancer Risk Rare but Recurrent Nick Mulcahy From Medscape Medical News > Oncology


July 20, 2012 — A new study has confirmed that a genetic mutation significantly increases the risk for prostate cancer, especially early-onset and familial cancers, in white men.
The study was published online July 9 in the Journal of the National Cancer Institute and moves academic research a step closer to a possible commercial test.
The new study comes about 6 months after a groundbreaking article was published on the discovery of the mutation. That article established the G84E mutation as the first major genetic variant associated with inherited prostate cancer.
The G84E mutation occurs in the HOXB13 gene, which is important in prostate development. However, the mutation is rare: In the new study, it occurred in less than 1% of the men.
The mutation is detected using DNA sequencing.
"This new genetic test is one more tool in the arsenal to potentially identify patients who may benefit from earlier or additional screening," Robert Nam, MD, lead author of the new study, said in a news release. Dr. Nam is from the Odette Cancer Centre at Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
The new study involved 4068 men from the general population who were screened for prostate cancer and subsequently underwent a biopsy.
The researchers identified and compared the frequency of HOXB13 mutations in 2 groups: 1843 men subsequently diagnosed with the disease and 2225 men who were disease-free (control patients).
The mutation was only found among white men, not among any of the other ethnic groups in the study. As a result, the authors concentrated their analysis on the white men. The G84E mutation was 7 times more frequent in white men with prostate cancer compared with white control patients. Namely, 10 (0.7%) of 1525 men with prostate cancer had the mutation vs 2 (0.1%) of 1759 control patients.
The frequency of the mutation was also more pronounced among men with prostate cancer who had early-onset disease or a family history of the illness compared with the control patients (1.6% vs 0.1%).
In both analyses, the presence of the mutation was associated with a statistically significant increased risk for prostate cancer.
Among the men with cancer who had early onset or a family history of the disease, the frequency of the mutation was 1 in 250. The carrier frequency for BRCA 1 and 2 mutations is about 1 in 300 to 1 in 800, according to press materials on the study.
Dr. Nam suggested that testing for the prostate cancer mutation may evolve into something akin to testing for BRCA mutations in certain women.
"For men with this gene mutation, especially younger men at higher risk, similar to women with BRCA mutations at increased risk for breast and ovarian cancer, our goal is to extend lives as much as possible to their expected years of living through more proactive and better informed interventions," said Dr. Nam.
Unknowns With Testing
There are 3 "big questions" that remain unanswered about using a test to detect the G84E mutation in men, said Kathleen Cooney, MD, from the University of Michigan Medical School in Ann Arbor. Dr. Cooney was the lead author of an article published earlier this year on the discovery of the mutation. She spoke with Medscape Medical News about the new study.
The questions are, Who to test? When to test? And how does this affect clinical decision making? Dr. Cooney said.
The test will likely be used in men with a family history of prostate cancer or in young men who are somehow identified as more likely to have the mutation, she said. Nevertheless, "it isn't going to be a widely used test," said Dr. Clooney.
The timing of testing is an unknown because carriers will have had the mutation since birth, which invites the question of how soon to test, she pointed out.
In addition, when men are mutation positive, it is not yet known how to proceed clinically, Dr. Clooney said.
However, the new study advances the state of knowledge about the mutation in a number of ways, she said.
The study strengths are that is derived from a "random clinical sample," she said. That makes it different from her earlier study, which included an "enriched" population of group of families with a pronounced history of prostate cancer. Thus, Dr. Cooney's team found a slightly higher frequency of the mutation. The new study was also large, and "therefore powered to detect the impact of a rare mutation," she said.
J Natl Cancer Inst. Published online July 9, 2012. Abstract

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