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BRCA1/2 ATM Mutations ID Risk for Lethal Prostate Cancer

After adjustment for covariates, mutation carrier remained independent predictor of lethal PCa

genetic helix

FRIDAY, Dec. 16, 2016 (HealthDay News) -- The rate of germline BRCA1/2 and ATM mutations is significantly higher among patients with lethal prostate cancer (PCa) and is an independent predictor of lethal PCa, according to a study published online Dec. 15 in European Urology.

Rong Na, from Fudan University in Shanghai, and colleagues directly assessed whether germline mutations in BRCA1/2 and ATM distinguish lethal from indolent PCa. Data were included from a retrospective study of 313 patients who died of PCa and 486 with low-risk localized PCa of European, African, and Chinese descent. Germline DNA from all patients was sequenced for these genes.

The researchers found that lethal PCa patients had a significantly higher combined BRCA1/2 and ATM mutation rate compared with localized PCa patients (6.07 versus 1.44 percent; P = 0.0007). Among lethal PCa patients the rate also differed significantly as a function of age at death (P = 0.046) and time to death after diagnosis (P = 0.0006). After adjustment for race and age, prostate-specific antigen, and Gleason score at the time of diagnosis, being a mutation carrier remained an independent predictor of lethal PCa (hazard ratio, 2.13; P = 0.004).

"Mutation status of BRCA1/2 and ATM distinguishes risk for lethal and indolent PCa and is associated with earlier age at death and shorter survival time," the authors write.

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