Breast cancer susceptibility genes (BRCA1 and BRCA2) influence the length of some women's fertile period, according to a global meta-analysis.
There have been conflicting results from studies of how BRCA mutations influence anti-Müllerian hormone (AMH) levels, which is used as an indicator of egg reserves. While some have found that the BRCA1 mutation lower AMH levels (see BioNews 848), others have failed to reproduce this. Now, an international group of scientists including some from Yale School of Medicine, Connecticut, report that BRCA1 but not BRCA2 mutations reduce AMH levels.
Professor Kutluk Oktay, director of Laboratory of Molecular Reproduction and Fertility Preservation at Yale, and study leader, said, 'These results can translate into a ten-year shortening of reproductive life period in these women, which means that women with BRCA mutations should be vigilant about completing childbearing early and/or considering fertility preservation if delaying childbearing.'
Professor Oktay and colleagues investigated a large cohort of women with known BRCA status. They used five published datasets from which they were able to analyse the data from 824 women for the cohort study. Of these, 246 carried a BRCA1 and/or BRCA2 mutation while 578 were negative. The majority of the BRCA mutation carriers also had breast cancer.
The average level of AMH in the serum of BRCA1/2 carriers was 2.04 ng/mL versus 3.36 ng/mL in noncarriers. This was significantly lower after adjusting for age, smoking status, and oral contraceptive use. However, while the mean level of AMH was significantly lower in the women with just BRCA1 mutations versus controls, the same was not true for BRCA2 carriers.
'Although this meta-analysis could not demonstrate lower AMH levels in BRCA2 mutation carriers, this could be due to smaller sample size for the BRCA2 population,' Professor Oktay added.
Additionally, the results of this analysis may be influenced by the fact that most of the women with BRCA mutations also had breast cancer. Importantly, chemotherapy can also influence ovarian reserve. Therefore, further analyses in woman with BRCA mutations without breast cancer must be conducted.
Professor Oktay concluded, 'Cancer is a disease of ageing and these studies will not only help with future fertility counselling for women carrying DNA repair gene mutations but... may also unravel the mechanisms of ageing in general.'
The study was published in Journal of Clinical Oncology.
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