Prostate cancer risk heightened by gene mutations

A recent study has linked genetic mutations to an increased risk of developing prostate cancer.

Specifically, mutations in the gene butyrophilin-like 2 (BTNL2), which encodes a protein involved in regulating T-cell proliferation and cytokine production, were implicated in heightened risk of developing the disease.

For the study, which was published online in Cancer Epidemiology, Biomarkers & Prevention (Aug. 21, 2013), the authors studied multiple prostate cancer patients from families with a pattern of hereditary prostate cancer (HPC). Germline DNA provided by patients with more aggressive or early-onset disease was sequenced in an attempt to identify rare genetic mutations that predispose to prostate cancer. All the participants were men of European ancestry.

Several genes with candidate mutations were highlighted, but two coding variants in the BTNL2 gene were most strongly related to the development of prostate cancer. These missense mutations that change the genetic code were subsequently confirmed to be clearly associated with prostate cancer in an independent set of HPC families and in a case-control study population.

The authors found that the two BTNL2 mutations associated with elevated prostate cancer risk are rare. In the 270 HPC families used for confirmation, about 1.5% of affected men carried one of the mutations but unaffected men carried none. In the population-based case-control study, 2% of prostate cancer cases and less than 1% of men without prostate cancer carried one of the variants.

In the case-control study, men who carried one of these variants had a significant 2.5- to 2.7-fold higher risk for developing prostate cancer compared to men who did not carry either mutation.

“This research demonstrates for the first time that rare mutations in the BTNL2 gene enhance susceptibility to both hereditary and sporadic prostate cancer,” said senior author Janet L. Stanford, PhD, of Fred Hutchinson Cancer Research Center in Seattle. Common variants in this gene have been previously linked to several autoimmune and inflammatory diseases such as sarcoidosis and ulcerative colitis.

The authors used whole-exome sequencing to identify genetic variations within 91 men from 19 HPC families. Then, 130 candidate mutations that were observed more frequently in the men with prostate cancer were evaluated in an independent set of 270 HPC families for further confirmation.

Other candidate mutations found in this whole-exome sequencing study will be evaluated in a future investigation involving a larger group of HPC families and case-control populations to further assess their link to prostate cancer.

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