Highest Genetic Risk Group Has 5-fold Higher Risk of Prostate Cancer

The risk for developing prostate cancer is more than 5 times higher for men in the top 1% of the genetic risk score group.
The risk for developing prostate cancer is more than 5 times higher for men in the top 1% of the genetic risk score group.

ORLANDO, FL The risk for developing prostate cancer is more than 5 times higher for men in the top 1% of the genetic risk score group compared with those with the median risk group, according to a study presented at 2017 Genitourinary Cancers Symposium.1

Genome-wide association studies (GWAS) identified greater than 100 prostate cancer susceptibility loci that have a role in the familial risk of prostate cancer in individuals of European ancestry. To identify additional susceptibility variants, Rosalind Eeles, PhD, of The Institute of Cancer Research in the United Kingdom, and colleagues conducted a prostate cancer GWAS larger than previous studies.

For the prostate component of the NCI Genetic Associations & Mechanisms in Oncology (GAME-ON) initiative, investigators analyzed genotypes from about 49,000 cases and 29,000 controls among individuals for European and Asian descent using the OncoArray platform. OncoArray consists of a 260K GWAS backbone, some common content, including fine-mapping of common cancer susceptibility loci, and cancer specific variants.

The researchers combined data from 82,308 genotypes of prostate cancer cases and 61,074 controls from several prostate cancer GWAS of European ancestry to conduct a meta-analysis of overall and aggressive prostate cancer risk. Of the cases, 20% were aggressive disease.

Investigators identified 65 novel prostate cancer susceptibility loci, including 2 single nucleotide polymorphisms (SNPs) associated with early-onset prostate cancer in individuals 55 years of age or younger and 4 associated with both aggressive and indolent disease. Their analysis also captured an additional 6% of the familial relative risk.

Dr Eeles and her colleagues estimate that common variants capture 26% of the familial relative risk, rare SNPs comprise 5% to 6%, the newly identified SNPs capture 6%, and 62% remain unexplained.

"Up until these results, we were really having trouble finding SNPs associated with aggressive disease," noted Dr Eeles.

In risk stratification, men in the top 1% of the genetic risk score group have a 5.72-fold higher risk for developed prostate cancer compared with the median risk group in the middle fiftieth percentile (relative risk [RR], 5.72; 95% CI, 5.04-6.49). Men in the ninetieth to ninety-ninth percentile have a 2.71 times higher risk than the median group (RR, 2.71; 95% CI, 2.57-2.84).

RELATED: Targeting AR Mutations Promising In Prostate Cancer

"We all know that prostate cancer is the most common solid tumor, particularly in the Western world, and the second most common cause of [cancer-related] death," said Dr Eeles. "So it is really incumbent on us to do the right tests as a result of these genetic findings to see if they are really going to help in targeted screening."

Reference

  1. Eeles R, Amin Al Olama A, Berndt S, et al. Prostate cancer meta-analysis from more than 145,000 men to identify 65 novel prostate cancer susceptibility loci. Paper presented at: 2017 Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.

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