Breast cancer susceptibility loci in association with age at menarche, age at natural menopause and the reproductive lifespan.

PubMed ID: 24373701

Author(s): Warren Andersen S, Trentham-Dietz A, Gangnon RE, Hampton JM, Skinner HG, Engelman CD, Klein BE, Titus LJ, Egan KM, Newcomb PA. Breast cancer susceptibility loci in association with age at menarche, age at natural menopause and the reproductive lifespan. Cancer Epidemiol. 2014 Feb;38(1):62-5. doi: 10.1016/j.canep.2013.12.001. Epub 2013 Dec 25. PMID 24373701

Journal: Cancer Epidemiology, Volume 38, Issue 1, Feb 2014

BACKGROUND Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Some of these loci have unknown functional significance and may mediate the effects of hormonal exposures on breast cancer risk. We examined relationships between breast cancer susceptibility variants and menstrual/reproductive factors using data from two population-based studies.

METHODS The first analysis was based on a sample of 1328 women age 20-74 who participated as controls in a case-control study of breast cancer conducted in three U.S. states. We evaluated the associations between age at menarche, age at natural menopause and the reproductive lifespan with 13 previously identified breast cancer variants. Associations were also examined with a genetic score created as the sum of at-risk alleles across the 13 variants. For validation, significant results were evaluated in a second dataset comprised 1353 women age 43-86 recruited as part of a cohort study in Wisconsin.

RESULTS Neither the genetic score nor any of the 13 variants considered individually were associated with age at menarche or reproductive lifespan. Two SNPs were associated with age at natural menopause; every increase in the minor allele (A) of rs17468277 (CASP8) was associated with a 1.12 year decrease in menopause age (p=0.02). The minor allele (G) of rs10941679 (5p12) was associated with a 1.01 year increase in age at natural menopause (p=0.01). The results were not replicated in the validation cohort (B=-0.61, p=0.14 and B=-0.01, p=.0.98, respectively).

CONCLUSIONS The evaluated variants and reproductive experiences may work through separate pathways to influence breast cancer risk.