Increased cancer risk in infertile men is explained by genetic predisposition

A study conducted by researchers at the University of Tartu showed a nearly five-fold enrichment of hereditary cancer variants in infertile compared to fertile men.

Every 10^th man suffers from sub- or infertility, and it is an independent risk factor for several chronic diseases. According to Anu Valkna, a Junior Research Fellow in the Chair of Human Genetics at the University of Tartu and one of the study's authors, previous research has shown that men with lower sperm counts have an increased risk of developing cancer during their lifetime. "Previous studies have also shown that not only infertile men but also their relatives have a higher risk of cancer. We explored whether these observations could be explained by genetic predisposition," she said.

In collaboration with the Andrology Clinic of Tartu University Hospital, over 500 men with unexplained infertility were studied to determine a possible genetic cancer predisposition. An analysis pipeline developed by the Chair of Human Genetics at the University of Tartu was used to assess more than 150 hereditary cancer genes.

The data showed a nearly five-fold higher load of hereditary cancer-linked findings in infertile men compared to fertile men. "We found that among infertile men, every 15th infertile man carried a predisposing genetic variant, compared to one in 64 fertile men. This may explain why infertile men have a higher cancer risk - they already have a genetic predisposition that makes the body more susceptible to cancer," said Valkna. The researchers also found that several patients had been diagnosed with cancer by the time the study was conducted, and several had a family history of the disease. "This supports the hypothesis that there is a predisposition in these families. Unfortunately, we couldn't assess the prevalence of cancer among the patients as hereditary cancer syndromes are usually diagnosed later than the average age of those included in the study," Valkna added.

According to Anu Valkna, the study results have broader clinical implications. "We know that men seek medical attention for infertility at a younger age, usually before the progression and diagnosis of cancer. Therefore, early identification of predisposed patients would offer effective monitoring and early interventions. Moreover, since some hereditary cancer syndromes tend to disproportionately affect female family members, additional identification of at-risk family members would offer added clinical value to these families," she explained.

The article "Significantly increased load of hereditary cancer–linked germline variants in infertile men" was published in the high-impact factor journal Human Reproduction Open.