In an analysis of genetic information among more than 87,000 men, a global team of scientists says it has found 23 new genetic variants – common differences in the genetic code—that increase a man’s risk for prostate cancer. The so-called “meta-analysis,” believed to be the largest of its kind, has revealed once hidden mutations among men in a broad array of ethnic groups comprising men of European, African, Japanese and Latino ancestry.

The meta-analysis combined information from smaller studies, according to William B. Isaacs, Ph.D., a genetic scientist at the Brady Urological Institute at the Johns Hopkins University School of Medicine. “There is a power in numbers that helped us find new variants that were only hinted at in smaller study populations, especially among minority men, and as we found the same variants across several populations, the evidence became stronger that they were definitively linked to prostate cancer,” Isaacs said.

To help build the number of samples for the current study, described online Sept. 14 in Nature Genetics, Isaacs and Alan Partin, M.D., Ph.D., Brady Urological Institute director, contributed blood and tissue samples and data from 800 African-American men (400 with prostate cancer and 400 cancer-free) treated at Johns Hopkins to the study. All told, the samples included information on 43,303 prostate cancer patients and 43,737 men without prostate cancer.

Scientists at the Institute of Cancer Research and Royal Marsden National Health Services Foundation Trust in London, UK, and the University of Southern California led the analysis, which scanned more than 10 million areas of the genome where one genetic building block of DNA was switched for another, referred to as genetic variants, or more specifically, single-nucleotide polymorphisms (SNPs).

The team then compared the scanned genome regions of prostate cancer patients with prostate cancer-free men to find the 23 new SNPs they now link to prostate cancer. Together with 76 previously discovered SNPs, the variants account for one-third of the inherited risk for prostate cancers in men of European descent. Because the variants are inherited commonly among populations, they can appear in men with little or no family history of prostate cancer.

“Inheriting any single one of these genetic variants has only a small effect of prostate cancer risk,” says Partin. “However, a subset of men will inherit many of these variants, putting them at substantially increase risk for the disease, from three to six times the population average. Men with these risk levels may benefit from disease screening at earlier ages.”

Isaacs says that men with a family history of prostate cancer are already encouraged to be screened at an earlier age, “but family history may be difficult to pin down.”

He suggests that the identification of prostate cancer-related SNPS could serve as a “molecular family history” to enable better screening guidelines and therapies.

Overweight and obesity

Prostate cancer death risk, and aggressive prostate cancer risk, is 9-15% higher per 5-unit body mass index (BMI) increment, meta-analyses have shown. Localised prostate cancer risk is 4-6% lower per 5-unit BMI increment, meta-analyses have shown. This difference by prostate cancer aggressiveness may reflect difficulty detecting and treating prostate cancer in overweight and obese men.

Prostate cancer risk may be 30% higher in men in Europe with metabolic syndrome (characterised by overweight/obesity, ineffective insulin use, diabetes and hypertension), a meta-analysis showed; this may be mainly linked to hypertension and abdominal obesity.