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African Ancestry–Specific Variant May Be Linked to Familial Prostate Cancer Risk

By: Julia Fiederlein
Posted: Tuesday, August 11, 2020

Christopher A. Haiman, ScD, of the Keck School of Medicine, University of Southern California (USC), Los Angeles, and colleagues analyzed genetic data to determine whether the T risk allele rs72725854 is associated with several prostate cancer risk parameters in men of African ancestry. The results of this RESPOND study, which were published in European Urology, revealed this African ancestry–specific risk variant appeared to be significantly correlated with a younger age at diagnosis, more aggressive disease, and a family history of prostate cancer.

“About 12% of men of African ancestry carry this particular variant in the genome, which increases their risk twofold. The variant is not found in other populations,” Dr. Haiman commented in a USC press release. “This is a marker that may be used to identify African Americans and their family members who are at high risk and would benefit from more precise, targeted, and earlier prostate-specific antigen screening.”

This analysis aggregated data from 9,052 men of African ancestry with prostate cancer. Of these patients, 2,041 had high-risk disease, 692 had lethal disease, and 8,595 were identified as controls. A total of 143 high-risk familial cases were identified.

The African ancestry–specific variant was identified in 32% of high-risk familial cases, 23% of nonfamilial cases, and 12% of controls. In patients with at least two first-degree relatives with prostate cancer and at least one family member diagnosed before age 60, the odds ratio was higher among TT homozygotes (33.41) than TA heterozygotes (3.92). The absolute risks by age 60 for TA heterozygotic and TT homozygotic men with a family history of prostate cancer were 21% versus 38%, respectively. According to the investigators, rs72725854 accounts for more than 30% of the total familial risk caused by all known prostate cancer risk variants.

Disclosure: The study authors reported no conflicts of interest.



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