Genetic risk factors for cancer are associated with infertility

A genetic variant known to increase the risk of various cancers, including breast and ovarian cancers, has been linked to infertility in mice.

Researchers from Monash University in Melbourne, Australia, used mice to show that inhibiting BRCA1 – a gene that protects against cancer – impacted the litter size and quality of their eggs. Approximately 1 in 350 women have a mutation in their BRCA genes, which increases the risk of developing breast and ovarian cancer.

Senior author Professor Karla Hutt, head of the Monash Biomedicine Discovery Institute's (BDI) Ovarian Biology Laboratory and co-head of BDI's Development and Stem Cells Program, said: 'The potential impacts of complete loss of BRCA1 function on egg number and fertility had never been studied. Using a unique mouse model with targeted loss of the BRCA1 gene specifically in eggs, this study also comprehensively assessed fertility across the entire reproductive lifespan. The data show that BRCA1 is important for maintaining egg number, quality, and fertility.'

The research, published in Lancet's eBio Medicine Journal, used mice with the BRCA1 gene knocked out in their eggs to simulate the complete loss of function of the gene. They found that the lack of BRCA1 meant that the mice produced smaller litter sizes, and egg maturation rates decreased by 45 percent in reproductively aged mice – however their fertile lifespan length was not altered.

The researchers also looked at a small number of women and found that the level anti-Muellerian hormone – a test used to estimate the number of eggs they may have – did not correspond with egg numbers in women with BRCA mutations.

Co-first author Dr Amy Winship, also from Monash University, said: 'This has implications for women who carry BRCA mutations to make considered family planning and possibly fertility preservation decisions, like egg freezing. Additionally, since these women are already at higher risk of developing breast and ovarian cancer during their lifetime, they are more likely to receive fertility-damaging cancer treatments.'

A second recent study, published in the Journal of Clinical Endocrinology and Metabolism, looked at the link between cancer and infertility by studying cancer rates in women with primary ovarian insufficiency and their relatives.

The researchers conducted a population-based case-control study on patient records for cancer patients in Utah from 1995 to 2022. They found that women with primary ovarian insufficiency had an increased risk of breast, as well as ovarian cancer, while their second-degree relatives had an increased risk for breast and colon cancer. The risk of developing prostate cancer was also increased in first-, second- and even third-degree relatives of women with primary ovarian insufficiency.

While data on BRCA mutations was not evaluated for this second study, authors noted mutations in the BRCA genes are known to increase the risk for all the above cancers.