与初潮年龄、自然绝经年龄和生殖寿命相关的乳腺癌易感性基因座。
Breast cancer susceptibility loci in association with age at menarche, age at natural menopause and the reproductive lifespan.
机构信息
University of Wisconsin, Carbone Cancer Center, Madison, WI 53726, USA; Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
University of Wisconsin, Carbone Cancer Center, Madison, WI 53726, USA; Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
出版信息
Cancer Epidemiol. 2014 Feb;38(1):62-5. doi: 10.1016/j.canep.2013.12.001. Epub 2013 Dec 25.
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.
背景
全基因组关联研究已经确定了与乳腺癌风险相关的单核苷酸多态性（SNP）。其中一些基因座的功能意义尚不清楚，可能介导激素暴露对乳腺癌风险的影响。我们使用来自两个基于人群的研究的数据，研究了乳腺癌易感性变异与月经/生殖因素之间的关系。
方法
第一项分析基于 1328 名年龄在 20-74 岁的女性样本，这些女性作为三个美国州进行的乳腺癌病例对照研究的对照组参加了该研究。我们评估了初潮年龄、自然绝经年龄和生殖寿命与 13 个先前确定的乳腺癌变异之间的关系。还使用跨越 13 个变体的风险等位基因总和创建的遗传评分来检查关联。为了验证，在威斯康星州招募的作为队列研究一部分的 1353 名年龄在 43-86 岁的女性的第二个数据集上评估了显著结果。
结果
遗传评分或单独考虑的 13 个变体中的任何一个都与初潮年龄或生殖寿命无关。两个 SNP 与自然绝经年龄相关；rs17468277（CASP8）的次要等位基因（A）每增加一次，绝经年龄就会减少 1.12 岁（p=0.02）。rs10941679（5p12）的次要等位基因（G）与自然绝经年龄增加 1.01 岁相关（p=0.01）。这些结果在验证队列中没有得到复制（B=-0.61，p=0.14 和 B=-0.01，p=0.98，分别）。
结论
评估的变体和生殖经验可能通过单独的途径起作用，从而影响乳腺癌风险。
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