Male Fertility Problems in the Family Linked to Cancer Risk

Certain cancers were more likely among the families of men with fertility problems, according to a retrospective cohort study.

When researchers analyzed families of men with azoospermia (no sperm in the ejaculate), they observed significantly increased risks of bone and joint cancer, soft tissue cancer such as sarcoma, cancer of the womb, Hodgkin lymphoma, and thyroid cancer, reported Joemy Ramsay, PhD, of the University of Utah in Salt Lake City, and colleagues in Human Reproduction.

Families of men with severe oligozoospermia (low sperm counts, also known as oligospermia) had a significantly increased risk for cancers of the colon, bone and joints, and testes. On the other hand, there was a decreased risk of esophageal cancer among members of these families.

“Our study identified several unique patterns of cancer risk in families of men with poor fertility,” Ramsay said in a press release. “When family members share cancer risk patterns, it suggests that they have genetic, environmental, or health behaviors in common. Genetic and environmental exposures can also act together to increase cancer risk.”

“By identifying which groups of families have similar cancer risk patterns we can improve our understanding of the biological mechanisms of both cancer and infertility,” Ramsay added. “It will help us to assess the risk of cancer for families and provide improved patient counseling.”

In this study, the research team analyzed semen from 786 men and matched them with 5,674 fertile men in the general population. Their family members out to third-degree relatives were identified using the Utah Population Database. Cancer history for the family members was identified through the Utah Cancer Registry. Families with at least 10 members followed for at least 1 year from 1966 to 2017 were included in the analysis.

Among the men with fertility problems, 426 were azoospermic and 360 were severely oligozoospermic, with sperm concentrations of 0 and <1.5 million/mL, respectively.

Within each family, familial risk for each cancer type was measured, adjusting for sex, age, birth cohort, and person-years of follow-up for the family members.

The authors found that compared with control families, significant increases in cancer risks were observed for both the azoospermia and severe oligozoospermia cohorts.

Among azoospermia families, increased risk was seen for the following:

• Bone and joint cancer (HR 2.56, 95% CI 1.48-4.42)
• Soft tissue cancer (HR 1.56, 95% CI 1.01-2.39)
• Uterine cancer (HR 1.27, 95% CI 1.03-1.56)
• Hodgkin lymphoma (HR 1.60, 95% CI 1.07-2.39)
• Thyroid cancer (HR 1.54, 95% CI 1.21-1.97)

Among severe oligozoospermia families, increased risk was seen for colon cancer (HR 1.16, 95% CI 1.01-1.32), bone and joint cancer (HR 2.43, 95% CI 1.30-4.54), and testis cancer (HR 2.34, 95% CI 1.60-3.42).

On the other hand, a significant decrease in risk for esophageal cancer (HR 0.39, 95% CI 0.16-0.97) was observed among these families.

The authors identified 13 clusters of familial multicancer patterns in families of azoospermic men, with one cluster — which included the majority of families — demonstrating population-level cancer risks. The remaining 12 clusters, however, all had increased risks of developing at least one type of cancer.

Within the severe oligospermia cohort, Ramsay and colleagues identified 12 distinct familial multicancer clusters, all of which showed an elevated risk for at least one kind of cancer.

The authors noted that several clusters with elevated risks showed significantly increased odds of diagnosis at younger ages, particularly in cancers often seen in adolescents and young adults (AYAs), such as breast, thyroid, melanoma, testis, cervix, sarcoma, and lymphoma.

“AYA cancers have been shown to have distinct intrinsic and extrinsic risk factors, tumor biologies, and prognosis, with some studies showing unique mutational and genomic profiles relative to older adults,” wrote Ramsay and co-authors. “Additional study of why these cancers appear to coaggregate in the families of subfertile men could lead to improved understanding of AYA cancer and infertility etiology.”

Please enable JavaScript to view the

comments powered by Disqus.