Association of<i>BRCA1</i>Mutations with Impaired Ovarian Reserve: Connection Between Infertility and Breast/Ovarian Cancer Risk

Giordano, Sara; Garrett‐Mayer, Elizabeth; Mittal, Navdha; Smith, Kristin; Shulman, L.P.; Passaglia, C.; Gradishar, William J.; Pavone, Mary Ellen

doi:10.1089/jayao.2016.0009

Cited by 62 publications

(65 citation statements)

References 28 publications

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“…(35) Another study examining 124 BRCA1 carriers and controls observed that BRCA1 carriers have increased odds of low AMH but only among women older than 35. (36)…”

Section: Discussionmentioning

confidence: 99%

Antimüllerian hormone levels are lower in BRCA2 mutation carriers

Johnson

Sammel

Domchek

et al. 2017

Fertility and Sterility

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Objective To compare Anti-Mullerian Hormone (AMH) levels in women at high risk for hereditary breast and ovarian cancer compared to healthy, low-risk controls. Design Prospective cohort Setting Ambulatory Patient(s) Reproductive age women with a uterus and both ovaries were analyzed in four groups: BRCA1 carriers, BRCA2 carriers, BRCA negative, and low-risk controls Intervention(s) Self-collected dried blood spot (DBS) Main Outcome Measure(s) AMH levels Result(s) One hundred ninety-five women were included: 55 BRCA1 carriers, 50 BRCA2 carriers, 26 BRCA negative, and 64 low-risk controls. After adjusting for confounders, BRCA2 carriers had AMH levels that were 33% lower than controls (Geometric Mean Ratio(GMR)=0.67, 95% CI 0.47–0.94) and an increased odds of having AMH<1 ng/mL (OR 3.69, 95% CI 1.34–10.19). BRCA1 carriers and BRCA negative women had similar AMH levels to controls. When analysis was restricted to regularly menstruating women younger than 40, BRCA2 carriers continued to demonstrate significantly lower AMH levels and increased likelihood of low AMH. Also, in this restricted group, BRCA negative women demonstrated AMH levels that were 42% lower than controls (GMR=0.58; 95%CI 0.35–0.95). No difference in AMH was observed among BRCA1 carriers. Conclusion(s) We observed significantly lower AMH levels among BRCA2 carriers compared to low-risk controls. These results were stable across all models. BRCA negative women also had lower AMH values, but only in models restricted to young, regularly menstruating women. In contrast to previous analyses, BRCA1 carriers had AMH values that were similar to low-risk controls, but this may be due to differences in the population studied.

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“…(35) Another study examining 124 BRCA1 carriers and controls observed that BRCA1 carriers have increased odds of low AMH but only among women older than 35. (36)…”

Section: Discussionmentioning

confidence: 99%

Antimüllerian hormone levels are lower in BRCA2 mutation carriers

Johnson

Sammel

Domchek

et al. 2017

Fertility and Sterility

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“…There is a significant evidence from small studies on women with BRCA1 mutations that these individuals have low ovarian reserve and poor response to fertility treatments. 7,117 There are few studies which fail to associate the link between BRCA1 and BRCA2 gene mutations, age of menopause, fertility problems, and parity. 118,119 Nonetheless, the converse, whether POI in itself carries a higher risk for breast, ovarian, or other forms of cancer is currently unknown.…”

Section: Accelerated Ovarian Aging and Adverse Health Outcomesmentioning

confidence: 99%

Genetics of Reproductive Aging from Gonadal Dysgenesis through Menopause

Desai

Rajkovic

2017

Semin Reprod Med

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Reproduction is essential for the survival of the species and is influenced by external factors such as smoking and exposure to chemotherapy as well as chronic disorders such as obesity and autoimmunity. Reproductive senescence, such as menopause, is also dependent on multiple intrinsic genetic factors. Reproductive aging is not isolated from an overall aging process, and several studies strongly support the link between the early age of menopause and mortality. The extreme form of reproductive aging is primary ovarian insufficiency (POI) with prevalence ranging from 1 to 5% of the female population. POI has been shown to have long-term consequences on overall health. POI and age of menopause have a significant hereditary component. The population-based genome-wide association studies have identified 44 genomic loci to associate with age of menopause, and 29 of 44 loci harbor DNA damage response genes. Recent application of whole exome sequencing on carefully selected families with POI has also revealed a significant contribution of DNA damage response genes. The inability to repair the DNA damage in both somatic and germ cells might be a predisposing factor for the link between reproductive and overall aging in a subset of individuals with POI. The aim of this review is to characterize recent advances in the genetics of POI and its link with overall health.

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“…Another potential common mechanism between cancer and infertility is the presence of mutations in genes associated with DNA repair (e.g. BRCA) that may increase the risk of both conditions (Giordano et al, 2016;Johnson et al, 2017). In summary, our findings suggest an association between infertility and higher risk of cancer compared to a population deemed by claimsbased criteria to be non-infertile.…”

Section: Subset Analysesmentioning

confidence: 56%

Risk of cancer in infertile women: analysis of US claims data

Murugappan

Lathi

et al. 2019

Human Reproduction

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Is female infertility associated with higher risk of cancer? SUMMARY ANSWER: Although absolute risks are low, infertility is associated with higher risk of cancer compared to a group of noninfertile women. WHAT IS KNOWN ALREADY: Infertile women are at higher risk of hormone-sensitive cancers. Information on risk of non-gynecologic cancers is rare and conflicting, and the effect of pregnancy on these risk associations is known for only a minority of cancer types.

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Association ofBRCA1Mutations with Impaired Ovarian Reserve: Connection Between Infertility and Breast/Ovarian Cancer Risk

Cited by 62 publications

References 28 publications

Antimüllerian hormone levels are lower in BRCA2 mutation carriers

Antimüllerian hormone levels are lower in BRCA2 mutation carriers

Genetics of Reproductive Aging from Gonadal Dysgenesis through Menopause

Risk of cancer in infertile women: analysis of US claims data

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