Genetic variants of age at menopause are not related to timing of ovarian failure in breast cancer survivors Journal Article


Authors: Homer, M. V.; Charo, L. M.; Natarajan, L.; Haunschild, C.; Chung, K.; Mao, J. J.; DeMichele, A. M.; Su, H. I.
Article Title: Genetic variants of age at menopause are not related to timing of ovarian failure in breast cancer survivors
Abstract: Objective: To determine if interindividual genetic variation in single-nucleotide polymorphisms (SNPs) related to age at natural menopause is associated with risk of ovarian failure in breast cancer survivors. Methods: A prospective cohort of 169 premenopausal breast cancer survivors recruited at diagnosis with stages 0 to III disease were followed longitudinally for menstrual pattern via self-reported daily menstrual diaries. Participants were genotyped for 13 SNPs previously found to be associated with age at natural menopause: EXO1, TLK1, HELQ, UIMC1, PRIM1, POLG, TMEM224, BRSK1, and MCM8. A risk variable summed the total number of risk alleles in each participant. The association between individual genotypes, and also the risk variable, and time to ovarian failure (>12 months of amenorrhea) was tested using time-to-event methods. Results: Median age at enrollment was 40.5 years (range 20.6-46.1). The majority of participants were white (69%) and underwent chemotherapy (76%). Thirty-eight participants (22%) experienced ovarian failure. None of the candidate SNPs or the summary risk variable was significantly associated with time to ovarian failure. Sensitivity analysis restricted to whites or only to participants receiving chemotherapy yielded similar findings. Older age, chemotherapy exposure, and lower body mass index were related to shorter time to ovarian failure. Conclusions: Thirteen previously identified genetic variants associated with time to natural menopause were not related to timing of ovarian failure in breast cancer survivors. © 2017 by The North American Menopause Society.
Keywords: breast cancer; genotype; ovarian failure; single-nucleotide polymorphisms; age at menopause
Journal Title: Menopause
Volume: 24
Issue: 6
ISSN: 1072-3714
Publisher: Lippincott Williams & Wilkins  
Date Published: 2017-06-01
Start Page: 663
End Page: 668
Language: English
DOI: 10.1097/gme.0000000000000817
PROVIDER: scopus
PMCID: PMC5443693
PUBMED: 28118297
DOI/URL:
Notes: Article -- Export Date: 3 July 2017 -- Source: Scopus
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  1. Jun J Mao
    100 Mao