Family members of men with fertility issues may have increased risk for some cancers
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Key takeaways:
- A man’s subfertility, infertility may have an association with increased cancer risk for extended family members.
- Risk magnitude is likely based on genetic or environmental factors.
Extended family members of men with severe subfertility or infertility may have an increased risk for several different cancer types, study results published in Human Reproduction showed.
The magnitude of that risk and which cancers individuals have a higher probability of developing vary, according to researchers. They identified multiple familial clusters in their study cohort that could be influenced by factors such as genetics and environment.
“We found 13 different multicancer patterns in the azoospermic [no sperm] families and 12 different multicancer patterns in oligozoospermic [limited sperm],” Joemy M. Ramsay, PhD, assistant professor at University of Utah, told Healio. “We found that there were different patterns between azoospermic families and oligozoospermic families, so it matters what type of subfertility the relative has in terms of what cancer patterns we’re seeing.”
Various cancers, cardiovascular and autoimmune diseases, “slightly” shorter lifespans, and increased mortality from chronic conditions in men have all been previously associated with poor quality and quantity of sperm, Ramsay said.
“A lot of those diseases [or] conditions can be linked with genetic and environmental factors, and a lot of genetic and environmental factors are shared with family members,” she continued. “We were curious — does this risk extend past the subfertile individual into their families? If so, can that help us learn some of the mechanistic underpinnings for these conditions? For infertility? For how they intersect?”
Ramsay and colleagues used the Subfertility Health and Assisted Reproduction and the Environment cohort to identify azoospermic and severely oligozoospermic (less than 1.5 × 106/mL) men, then used the Utah Population Database to find family members out to the third degree (to grandparents and their descendants) for their study.
They built cohorts using a ratio of 5:1 fertile men to subfertile/infertile men.
Families had to have at least 10 informative members and 1 or more years of follow-up between 1966 and 2017 to be included.
Researchers identified 426 case families and 3,105 control families for the azoospermic cohort and 360 case families and 2,569 control families for the ogliozoospermic cohort.
Azoospermic families had an increased risk for bone and joint, soft tissue, uterine, Hodgkin lymphoma and thyroid cancers compared with control famlies, and ogliozoospermic families had elevated risk for colon, bone and joint and testicular cancers. Ogliozoospermic families also had a reduced risk for esophageal cancer.
When examining familiar clusters, Ramsay and colleagues discovered 66% of azoospermic families had similar cancer risks as the general population. The other 12 clusters had increased risk for at least two different cancers. Additionally, most of those showed greater risk for cancer diagnoses at a younger age (risks ranged from twofold to 12-fold).
All the ogliozoospermic clusters displayed increased risk for at least one cancer, with a maximum of three, and five of those also showed elevated risk for adolescent and young adult cancers.
“There’s a lot of heterogeneity across families, which makes sense,” Ramsay said. “We can group different families together, but it still isn’t just a blanket — like if you’re related to someone who’s infertile you have increased cancer risk. It depends on the type of infertility, and it depends on the family.”
She noted how four of the 12 ogliozoospermic clusters had elevated risk for testicular cancer, but that ranged from fourfold to 24-fold.
“We’re still trying to figure out what those mechanisms are, and how we can identify and counsel those patients going forward,” Ramsay said.
She hopes to investigate these clusters further, examining biospecimens, mutations or any other patterns connecting the families.
“For some of these families, we might be able to find some genes or combinations of genes — maybe something that has to do with [something] like mutation repair that could increase mutation rate, could cause infertility; increased mutation rate can [also] cause cancer,” Ramsay said.
“For others, it could be a shared environmental exposure,” she added. “Maybe they all live in an area that has some chemical exposure, and that’s impacting both of those factors for the family members and the infertile individual.”
For more information:
Joemy M. Ramsay, PhD, can be reached at joemy.ramsay@utah.edu.
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