生殖窗、基因位点与乳腺癌风险。
Reproductive windows, genetic loci, and breast cancer risk.
作者信息
Warren Andersen Shaneda, Trentham-Dietz Amy, Gangnon Ronald E, Hampton John M, Figueroa Jonine D, Skinner Halcyon G, Engelman Corinne D, Klein Barbara E, Titus Linda J, Egan Kathleen M, Newcomb Polly A
机构信息
University of Wisconsin Carbone Cancer Center, Madison; Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
University of Wisconsin Carbone Cancer Center, Madison; Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
出版信息
Ann Epidemiol. 2014 May;24(5):376-82. doi: 10.1016/j.annepidem.2014.02.007. Epub 2014 Mar 2.
PURPOSE
The reproductive windows between age at menarche and age at first birth (standardized age at first birth) and from menarche to menopause (reproductive lifespan) may interact with genetic variants in association with breast cancer risk.
METHODS
We assessed this hypothesis in 6131 breast cancer cases and 7274 controls who participated in the population-based Collaborative Breast Cancer Study. Risk factor information was collected through telephone interviews, and DNA samples were collected on a subsample (N= 1484 cases, 1307 controls) to genotype for 13 genome-wide association study-identified loci. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and P values for the interaction between reproductive windows and genotypes were obtained by adding cross-product terms to statistical models.
RESULTS
For standardized age at first birth, the OR was 1.52 (CI, 1.36-1.71) comparing the highest quintile with the lowest quintile. Carrier status for rs10941679 (5p12) and rs10483813 (RAD51B) appeared to modify this relationship (P = .04 and P = .02, respectively). For reproductive lifespan, the OR comparing the highest quintile with the lowest quintiles was 1.62 (CI, 1.35-1.95). No interactions were detected between genotype and reproductive lifespan (all P > .05). All results were similar regardless of ductal versus lobular breast cancer subtype.
CONCLUSIONS
Our results suggest that the reproductive windows are associated with breast cancer risk and that associations may vary by genetic variants.
目的
月经初潮年龄与首次生育年龄（标准化首次生育年龄）之间以及从月经初潮到绝经（生殖寿命）的生殖窗口可能与乳腺癌风险相关的基因变异相互作用。
方法
我们在参与基于人群的协作性乳腺癌研究的6131例乳腺癌病例和7274例对照中评估了这一假设。通过电话访谈收集危险因素信息，并在一个子样本（n = 1484例病例，1307例对照）中收集DNA样本，对13个全基因组关联研究确定的位点进行基因分型。计算调整后的比值比（OR）和95%置信区间（CI），并通过在统计模型中添加交叉乘积项获得生殖窗口与基因型之间相互作用的P值。
结果
对于标准化首次生育年龄，将最高五分位数与最低五分位数进行比较，OR为1.52（CI，1.36 - 1.71）。rs10941679（5p12）和rs10483813（RAD51B）的携带者状态似乎改变了这种关系（分别为P = 0.04和P = 0.02）。对于生殖寿命，将最高五分位数与最低五分位数进行比较，OR为1.62（CI，1.35 - 1.95）。未检测到基因型与生殖寿命之间的相互作用（所有P > 0.05）。无论乳腺癌亚型是导管癌还是小叶癌，所有结果均相似。
结论
我们的结果表明，生殖窗口与乳腺癌风险相关，并且这种关联可能因基因变异而异。
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