Conference Coverage

Prostate cancer susceptibility loci identified



A large analysis has identified 65 novel prostate cancer susceptibility loci, including an early-onset locus, and captured an additional 6% of the familial relevant risk for prostate cancer.

In the Oncoarray stratified analysis, the researchers detected two single nucleotide polymorphisms (SNPs) that were associated with early-onset prostate cancer, defined as disease occurring in men younger than 55 years, and four that were associated with both aggressive and indolent disease.

“But there were none that were only specifically for aggressive disease,” lead author Rosalind Eeles, PhD, of the Institute of Cancer Research in London, said at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

“By the end of this year we will have a genetic test with 170 variants, and men at the top of 1% of risk group would have a 5.72% risk over the average man,” she said. “But if we incorporated in the rarer variants, which are associated with very nasty disease, could we then start to identify men who are at risk for aggressive disease, and if so, how should we intensively screen them or even treat them?”

Currently genome-wide association studies (GWAS) have identified over 100 prostate cancer susceptibility loci, which included 33% of the prostate cancer familial relative risk in Europeans.

“We already know how to stratify populations into risk groups,” said Dr. Eeles. “It is important for us to do the right tests to see if they are really going to help in terms of targeted screening.”

The heritability of prostate cancer is 57%, but currently there are no common aggressive-disease markers.

To identify further susceptibility variants, Dr. Eeles and her colleagues conducted a prostate cancer GWAS that was far larger than previous investigations. Their analysis included 46,939 prostate cancer cases and 27,910 controls of European ancestry who were genotyped using the 35,369 prostate cancer cases and 33,164 controls of European ancestry that were generated using other large-scale genotyping arrays.

Dr. Eeles explained that, because they want their data to be useful for future investigations and “you can’t type everything as just too expensive – there are millions of SNPs across the genome – we put in a GWAS backbone.”

What that means, she explained, is that, when these are typed, it can be inferred that the other genotypes are using mathematical modeling.

Their Oncoarray was a large sample consisting of various ethnic groups, but in this presentation Dr. Eeles focused on an analysis of 98.500 European samples. The number reached 145,000 because they combined it with previous results in a meta-analysis of samples derived from men of both European and Asian descent.

The identification of additional loci also will enable fine mapping efforts into the underlying biology of prostate cancer susceptibility, she added.

There was no funding source disclosed. Dr. Eeles has received honoraria from Janssen and Succinct Communications. Coauthor Peter Kraft reported a relationship with Merck, but none of the other investigators had any disclosures.

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