Choi Jungyoon, Jia Guochong, Wen Wanqing, Tao Ran, Long Jirong, Shu Xiao-Ou, Zheng Wei
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37203, USA.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37203, USA.
HGG Adv. 2021 Dec 10;3(1):100077. doi: 10.1016/j.xhgg.2021.100077. eCollection 2022 Jan 13.
Certain genetic variants are associated with risks of multiple cancers. We investigated breast cancer risk with overall genetic susceptibility to each of 16 other cancers. We constructed polygenic risk scores (PRS) for 16 cancers using risk variants identified by genome-wide association studies. We evaluated the associations of these PRSs with breast cancer risk (overall and by subtypes) using Breast Cancer Association Consortium data, including 106,278 cases and 91,477 controls of European ancestry. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated to measure the association of each PRS with breast cancer risk. Data from the UK Biobank, including 4,337 cases and 209,983 non-cases, were used to replicate the findings. A 5%-8% significantly elevated risk of overall breast cancer was associated with per unit increase of the PRS for glioma and cancers of the corpus uteri, stomach, or colorectum. Analyses by subtype revealed that the PRS for corpus uteri cancer (OR = 1.09; 95% CI, 1.03-1.15) and stomach cancer (OR = 1.07; 95% CI, 1.03-1.12) were associated with estrogen receptor-positive breast cancer, while ovarian cancer PRS was associated with triple-negative breast cancer (OR = 1.25; 95% CI, 1.01-1.55). UK Biobank data supported the positive associations of overall breast cancer risk with PRS for melanoma and cancers of the stomach, colorectum, and ovary. Our study provides strong evidence for shared genetic susceptibility of breast cancer with several other cancers. Results from our study help uncover the genetic basis for breast and other cancers and identify individuals at high risk for multiple cancers.
某些基因变异与多种癌症风险相关。我们研究了乳腺癌风险与对其他16种癌症的总体遗传易感性之间的关系。我们使用全基因组关联研究确定的风险变异构建了16种癌症的多基因风险评分（PRS）。我们利用乳腺癌协会联盟的数据评估了这些PRS与乳腺癌风险（总体及各亚型）之间的关联，该数据包括106278例病例和91477例欧洲血统对照。估计比值比（OR）和95%置信区间（CI）以衡量每个PRS与乳腺癌风险的关联。来自英国生物银行的数据，包括4337例病例和209983例非病例，用于重复这些发现。胶质瘤、子宫体癌、胃癌或结直肠癌的PRS每增加一个单位，总体乳腺癌风险显著升高5%-8%。按亚型分析显示，子宫体癌的PRS（OR = 1.09；95% CI，1.03 - 1.15）和胃癌的PRS（OR = 1.07；95% CI，1.03 - 1.12）与雌激素受体阳性乳腺癌相关，而卵巢癌的PRS与三阴性乳腺癌相关（OR = 1.25；95% CI，1.01 - 1.55）。英国生物银行的数据支持了总体乳腺癌风险与黑色素瘤、胃癌、结直肠癌和卵巢癌的PRS之间的正相关。我们的研究为乳腺癌与其他几种癌症存在共同的遗传易感性提供了有力证据。我们的研究结果有助于揭示乳腺癌和其他癌症的遗传基础，并识别患多种癌症风险较高的个体。
