Infertile males at higher risk for melanoma, prostate cancer

San Francisco-Risks of developing melanoma and prostate cancer are increased among those with a diagnosis of male factor infertility, according to researchers from the University of California, San Francisco. Their finding, presented at the AUA annual meeting in Orlando, FL, came from a study based on data from approximately 43,400 men.

Putting the results into perspective, the investigators cautioned that the research is very preliminary. Furthermore, the results indicate that men diagnosed with male factor infertility have an increased relative risk of certain malignancies, but the absolute risk of these cancers is still very low.

Dr. Walsh noted there has been accumulating evidence over the past several years, both from epidemiologic and preclinical studies, of an association between infertility and somatic cancers. Much of the evidence originated from studies in animal models and evolved from the field of epigenetics, which may help to explain how environmental factors relate to altered gene expression, altered fertility potential, and eventually the development of adverse health conditions later in life. Evidence that mutations in certain DNA repair genes are involved in both infertility and cancer suggest a possible link.

Dr. Walsh and colleagues turned to a cohort of infertile couples who had been assembled for a previous research study and could provide subgroups of men with and without male factor infertility. Rates of subsequent cancer development among the male partners were determined through linkage with the Surveillance, Epidemiology, and End Results cancer registries in California.

Compared to an age-matched sample of men from the general population, the men from couples with infertility had a lower rate of all cancers, but were more likely to be diagnosed with prostate cancer and melanoma.

"Our initial assertion to explain the latter higher cancer rates would be that it reflects a screening phenomenon, especially for prostate cancer that is predominantly diagnosed by screening," Dr. Walsh said.

Expanding the study

A time-to-disease analysis was performed to investigate whether male factor infertility in itself was a cancer risk factor. Results showed that compared to men in the cohort without male factor infertility, those carrying the diagnosis were 1.5 times more likely to develop any cancer and 1.8 times more likely to be diagnosed with prostate cancer. Although there was a trend for male factor infertility being a risk factor for melanoma, this finding did not reach statistical significance.

Now the researchers are extending their investigations using the current cohort to conduct a case-cohort study in order to estimate relative risk of cancer based on the assumption that this large population of men evaluated for infertility is a reflection of the general population. Attempts will be made to contact men diagnosed with certain cancers and, within a subcohort, to compare various exposures, comorbidities, and other health-related conditions to determine specific risk factors for both infertility and cancer.

The investigators are also endeavoring to establish other large cohorts of infertile men and will be studying them in comparison to populations comprised of men with proven paternity.

"Male infertility is a condition that has been understudied but warrants investigation because of its potential impact on human reproductive potential overall," Dr. Walsh said.

"The findings from our study suggesting an association between male infertility and cancer may be a reflection of certain epigenetic and genetic phenomena; perhaps male factor infertility is the first sign of more severe diseases that would be seen later in life. In that regard, we may be seeing a snapshot of evolution during a single generation where people who are most susceptible to adverse disease outcomes do not have as good a reproductive potential."

Dr. Walsh observed that previous population-based research exploring an association between male infertility and testicular cancer has been conducted in countries outside of the United States, particularly Denmark and Sweden.

"Unfortunately, male infertility is not a reportable disease in the U.S., and so it has been very difficult to assemble a large cohort of men who seek infertility evaluation to see if this type of association exists," he said.