Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States.
Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States.
Sci Rep. 2020 Feb 24;10(1):3242. doi: 10.1038/s41598-020-60032-3.
Most gene-environmental studies have focused on breast cancers generally, the preponderance of which occur after age 50. Young-onset breast cancers (YOBC) tend to be aggressive and may be etiologically different. The goal of this analysis was to assess interactions between an established 77-SNP polygenic risk score (PRS) and non-genetic risk factors for YOBC. We constructed the PRS using a family-based study of 1,291 women diagnosed with breast cancer before age 50 and their parents and unaffected sisters. We used conditional logistic regression to analyze interactions between the PRS and 14 established risk factors. In further analyses we assessed the same interactions, but for invasive cancer, estrogen receptor (ER) positive cancer and with broader inclusion of racial/ethnic groups. Results showed a decreased association between the PRS and YOBC risk for women who had ever used hormonal birth control (odds ratio [OR] = 2.20 versus 3.89) and a stronger association between the PRS and YOBC risk in pre-menopausal women (OR = 2.46 versus 1.23). Restricting the analysis to ER+ cancers or invasive cancers or using samples from all ethnic groups produced similar results. In conclusion, the PRS may interact with hormonal birth control use and with menopausal status on risk of YOBC.
大多数基因-环境研究都集中在一般的乳腺癌上，其中绝大多数发生在 50 岁以后。年轻发病的乳腺癌（YOBC）往往具有侵袭性，其病因可能不同。本分析的目的是评估已建立的 77-SNP 多基因风险评分（PRS）与 YOBC 的非遗传风险因素之间的相互作用。我们使用了一项基于家族的研究，该研究包括 1291 名 50 岁前被诊断患有乳腺癌的女性及其父母和未受影响的姐妹。我们使用条件逻辑回归分析了 PRS 与 14 个已确立的风险因素之间的相互作用。在进一步的分析中，我们评估了相同的相互作用，但针对浸润性癌症、雌激素受体（ER）阳性癌症，并更广泛地纳入了种族/民族群体。结果表明，对于曾经使用过激素避孕的女性，PRS 与 YOBC 风险之间的关联减弱（比值比 [OR] = 2.20 与 3.89），而 PRS 与年轻发病乳腺癌风险之间的关联在绝经前女性中更强（OR = 2.46 与 1.23）。将分析仅限于 ER+癌症或浸润性癌症，或使用所有种族群体的样本，得到了类似的结果。总之，PRS 可能与激素避孕的使用以及与绝经状态相互作用，影响 YOBC 的风险。
