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Research identifies cancer risk patterns in families of men with fertility problems

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Research identifies cancer risk patterns in families of men with fertility problems

For the primary time researchers have identified patterns of risk for several various kinds of cancer in men with fertility problems and their families.

The study, which is published today (Thursday) in Human Reproduction, considered one of the world’s leading reproductive medicine journals, found that families of men who’ve only a few or no sperm of their semen have a better risk of developing cancer, including developing cancer at younger ages, in comparison with families of fertile men.

The danger and the sort of cancer varied greatly depending on whether the boys had low numbers of sperm (oligozoospermic) or none (azoospermic), with several cancers identified in distinct clusters of families.

The researchers, led by Dr Joemy Ramsay, assistant professor on the University of Utah, Salt Lake City, USA, hope their findings will improve their understanding of the biological mechanisms involved in each cancer and infertility. This may enable doctors to make more accurate predictions of risk of cancer for men with fertility problems and their families, and to enhance the counselling that might be offered to them.

Previous research has shown that male infertility is linked to an increased risk of cancer in the boys and their families, but the outcomes have been inconsistent. Increased risks and the sorts of cancer varied considerably between family groups and depending on whether the boys were oligozoospermic or azoospermic.

On this study, we wanted to explain the extent to which patterns of cancer risk vary between families of subfertile men, and whether this risk is seen in all families or is driven by a small subset of families, akin to the way in which mutations within the BRCA gene increase the danger of breast cancer in families that carry this mutation. By identifying families with similar patterns of cancer, we may give you the chance to find aspects which are involved in each infertility and cancer.”

 Dr Joemy Ramsay, Assistant Professor, University of Utah, Salt Lake City

Dr Ramsay and colleagues took results from semen analyses carried out between 1996 and 2017 from 786 men attending fertility clinics in Utah, they usually matched them with information from 5674 fertile men in the overall population who had at the least one child to make sure they were fertile. Amongst the boys with fertility problems, 426 were azoospermic and 360 were severely oligozoospermic (with lower than 1.5 million sperm per millilitre of semen).

The researchers collected information on first, second and third degree relatives using the Utah Population Database. Cancer diagnoses were identified from the Utah Cancer Registry.

“We concurrently assessed the danger for multiple sorts of cancer inside each family after which we performed a cluster evaluation to seek out groups of families with similar patterns of risk for multiple cancers,” said Dr Ramsay. “That is the primary study to explain these multicancer patterns in families of subfertile men.”

When the researchers checked out all families of azoospermic men, they saw a significantly increased risk of 5 cancers: bone and joint cancer (156% increased risk), soft tissue cancers similar to sarcomas (56% increased risk), cancers of the womb (27% increased risk), Hodgkin Lymphomas (60% increased risk), and thyroid cancers (54% increased risk).

Families of the severely oligozoospermic men had a significantly increased risk of three cancers: colon cancer (16% increased risk), bone and joint (143% increased risk), and testicular cancer (134% increased risk). The researchers also found a 61% decreased risk of oesophageal cancer (cancer of the gullet).

The researchers found the danger of cancer and the sorts of cancer varied greatly among the many families of men with fertility problems, each by sort of subfertility and likewise inside subfertility type. This might explain the inconsistent associations between subfertility and cancer in previous studies. For instance, the study found an increased risk of testicular cancer in just a 3rd of the clusters of families of oligozoospermic men, however the increased risk ranged from four- to 24-fold depending on family cluster.

Among the many families of azoospermic men, the researchers identified 13 clusters of families. One cluster, which included nearly all of the families, had a risk of cancer that was much like that in the overall population. Nonetheless, the remaining 12 clusters all had increased risks of developing at the least one sort of cancer. Among the many families of oligozoospermic men, there have been 12 distinct clusters and all of them had an increased risk for at the least one sort of cancer.

“Our study identified several unique patterns of cancer risk in families of men with poor fertility. When relations share cancer risk patterns, it suggests that they’ve genetic, environmental, or health behaviours in common. Genetic and environmental exposures also can act together to extend cancer risk. By identifying which groups of families have similar cancer risk patterns we are able to improve our understanding of the biological mechanisms of each cancer and infertility,” said Dr Ramsay. “It is going to help us to evaluate the danger of cancer for families and supply improved patient counselling.”

The researchers have carried out genetic sequencing studies to search for specific genetic mutations that could be driving the associations between subfertility and cancer seen on this study.

Strengths of the study include the use of information from population registries for family structure, cancer diagnosis and subfertility. Limitations include lack of semen measures for the fertile men, lack of knowledge on other health conditions, lifestyle risk aspects, similar to smoking and body mass index, and exposure to environmental risk aspects among the many subfertile men; and, finally, that the boys with fertility problems on this study were all seen at a fertility clinic and, due to this fact, represent a subset of the general population of subfertile men who had the socioeconomic means to be evaluated by a health care provider.

Source:

Journal reference:

Ramsay, J. M., et al. (2024) Describing patterns of familial cancer risk in subfertile men using population pedigree data. ​​ Human Reproduction. doi.org/10.1093/humrep/dead270.

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