title: Genetic variants of age at menopause are not related to timing of ovarian failure in breast cancer survivors.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Thirteen previously identified genetic variants associated with time to natural menopause were not related to timing of ovarian failure in breast cancer survivors.
authors.affiliation: 1Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA 2Division of Biostatistics and Bioinformatics, University of California, San Diego, La Jolla, CA 3Moores Cancer Center, University of California, San Diego, La Jolla, CA 4Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 5Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA 6Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY 7Department of Internal Medicine and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Homer
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Charo
authors.forename: Loki
authors.initials: L
authors.lastname: Natarajan
authors.forename: Carolyn
authors.initials: C
authors.lastname: Haunschild
authors.forename: Karine
authors.initials: K
authors.lastname: Chung
authors.forename: Jun J
authors.initials: JJ
authors.lastname: Mao
authors.forename: Angela M
authors.initials: AM
authors.lastname: DeMichele
authors.forename: H Irene
authors.initials: HI
authors.lastname: Su
mesh_terms: D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008593:Menopause / Q000235:genetics*; D008594:Menopause, Premature / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017697:Premenopause; D011446:Prospective Studies; D013997:Time Factors