DNA-repair Gene Mutations More Frequent in Metastatic Prostate Cancer

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The incidence of germline mutations in genes mediating DNA-repair processes was significantly higher among men with metastatic prostate cancer.
The incidence of germline mutations in genes mediating DNA-repair processes was significantly higher among men with metastatic prostate cancer.

The incidence of germline mutations in genes mediating DNA-repair processes was significantly higher among men with metastatic prostate cancer compared with those with localized disease, according to a study published in The New England Journal of Medicine.1

Researchers prospectively assessed mutations in 20 DNA-repair genes associated with autosomal dominant cancer-predisposition syndrome in patients with metastatic prostate cancer.

For this multicenter study, investigators enrolled 692 men with documented metastatic disease who were unselected for family history of cancer or age at diagnosis. Germline DNA was isolated and multiplex sequencing assays were used to evaluate gene mutations.

There were a total of 84 germline DNA-repair gene mutations that were presumed to be deleterious in 11.8% of the 692 men.

Researchers identified mutations in 16 genes, including BRCA in 5.3%, ATM in 1.6%, CHEK2in 1.9%, BRCA1 in 0.9%, RAD51D in 0.4%, and PALB2 in 0.4%. There was no significant difference in the frequency of germline mutations according to age at diagnosis or family history of prostate cancer.

RELATED: Early Salvage Radiotherapy Recommended for Patients With Prostate Cancer Post-prostatectomy

The frequency of germline mutations in DNA-repair genes was significantly higher among men with metastatic prostate cancer, versus those with localized disease (11.8% versus 4.6%; P < .001), and versus those without a known cancer diagnosis (11.8% versus 2.7%; P < .001).

Reference

  1. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375:443-453.

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