Murphy Maureen E, Liu Song, Yao Song, Huo Dezheng, Liu Qin, Dolfi Sonia C, Hirshfield Kim M, Hong Chi-Chen, Hu Qiang, Olshan Andrew F, Ogundiran Temidayo O, Adebamowo Clement, Domchek Susan M, Nathanson Katherine L, Nemesure Barbara, Ambs Stefan, Blot William J, Feng Ye, John Esther M, Bernstein Leslie, Zheng Wei, Hu Jennifer J, Ziegler Regina G, Nyante Sarah, Ingles Sue A, Press Michael F, Deming Sandra L, Rodriguez-Gil Jorge L, Haiman Christopher A, Olopade Olufunmilayo I, Lunetta Kathryn L, Palmer Julie R, Ambrosone Christine B
Program in Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA 19104 USA.
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY 14263 USA.
NPJ Breast Cancer. 2017 Feb 27;3:5. doi: 10.1038/s41523-017-0007-9. eCollection 2017.
A coding region polymorphism exists in the gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia. We used multivariable logistic regression to estimate associations between the TP53 Pro47Ser allele and overall breast cancer risk. Because polymorphisms in tend to be associated with cancer risk in pre-menopausal women, we also limited our analyses to this population in the AMBER and ROOT consortia, where menopausal status was known, and conducted a fixed effects meta-analysis. In an analysis of all women in the AMBER, ROOT, and AABC consortia, we found no evidence for association of the Pro47Ser variant with breast cancer risk. However, when we restricted our analysis to only pre-menopausal women from the AMBER and ROOT consortia, there was a per allele odds ratio of 1.72 (95% confidence interval 1.08-2.76; -value = 0.023). Although the Pro47Ser variant was not associated with overall breast cancer risk, it may increase risk among pre-menopausal women of African ancestry. Following up on more studies in human populations may better elucidate the role of this variant in breast cancer etiology. However, because of the low frequency of the polymorphism in women of African ancestry, its impact at a population level may be minimal.
在非洲裔个体中，该基因存在一个编码区多态性（Pro47Ser；rs1800371），在小鼠模型中，这会降低p53肿瘤抑制功能。目前尚不清楚这种具有功能意义的多态性是否会改变人类患癌风险。该分析纳入了来自AMBER、ROOT和AABC联盟的6907名乳腺癌女性患者和7644名对照。我们使用多变量逻辑回归来估计TP53 Pro47Ser等位基因与总体乳腺癌风险之间的关联。由于该基因的多态性往往与绝经前女性的癌症风险相关，我们还将分析限制在AMBER和ROOT联盟中已知绝经状态的该人群，并进行了固定效应荟萃分析。在对AMBER、ROOT和AABC联盟的所有女性进行的分析中，我们没有发现Pro47Ser变体与乳腺癌风险相关的证据。然而，当我们将分析仅限于AMBER和ROOT联盟中的绝经前女性时，每个等位基因的优势比为1.72（95%置信区间1.08 - 2.76；P值 = 0.023）。虽然Pro47Ser变体与总体乳腺癌风险无关，但它可能会增加非洲裔绝经前女性的患病风险。开展更多针对人群的研究可能会更好地阐明该变体在乳腺癌病因学中的作用。然而，由于非洲裔女性中该多态性的频率较低，其在人群层面的影响可能很小。
