Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan.
Karmanos Cancer Institute, Detroit, Michigan.
Cancer Epidemiol Biomarkers Prev. 2023 Nov 1;32(11):1558-1563. doi: 10.1158/1055-9965.EPI-23-0174.
Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black populations in model development.
We used a previously published lung cancer PRS on the basis of 80 SNPs associated with lung cancer risk in the OncoArray cohort and validated in UK Biobank. The PRS was evaluated for association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of chronic obstructive pulmonary disease, and the top five principal components for genetic ancestry.
Among the 80 PRS SNPs included in the score, 14 were significantly associated with lung cancer risk (P < 0.05) in INHALE White participants, while there were no significant SNPs among INHALE Black participants. After adjusting for covariates, the PRS was significantly associated with risk in Whites (continuous score P = 0.007), but not in Blacks (continuous score P = 0.88). The PRS remained a statistically significant predictor of lung cancer risk in Whites ineligible for lung cancer screening under current U.S. Preventive Services Task Force guidelines (P = 0.02).
Using a previously validated PRS, we did find some predictive ability for lung cancer in INHALE White participants beyond traditional risk factors. However, this effect was not observed in Black participants, indicating the need to develop and validate ancestry-specific lung cancer risk models.
While a previously published lung cancer PRS was able to stratify White participants into different levels of risk, the model was not predictive in Blacks. Our findings highlight the need to develop and validate ancestry-specific lung cancer risk models.
多基因风险评分（PRS）已成为评估癌症易感性的一种越来越受欢迎的方法，但在模型开发中并未充分代表黑人人群。
我们使用了先前发表的基于 OncoArray 队列中与肺癌风险相关的 80 个 SNP 的肺癌 PRS，并在 UK Biobank 中进行了验证。该 PRS 用于评估与肺癌风险的关联，调整因素包括年龄、性别、总吸烟包年数、肺癌家族史、慢性阻塞性肺疾病史和遗传祖先的前五个主要成分。
在纳入评分的 80 个 PRS SNP 中，有 14 个与 INHALE 白人参与者的肺癌风险显著相关（P < 0.05），而 INHALE 黑人参与者中则没有显著的 SNP。在调整了协变量后，PRS 在白人中与风险显著相关（连续评分 P = 0.007），但在黑人中则不相关（连续评分 P = 0.88）。在目前美国预防服务工作组指南下不符合肺癌筛查条件的白人中，PRS 仍然是肺癌风险的统计学上显著预测因子（P = 0.02）。
使用先前验证的 PRS，我们确实发现 INHALE 白人参与者的肺癌风险除了传统风险因素外，还有一些预测能力。然而，这一效应在黑人参与者中并未观察到，这表明需要开发和验证特定种族的肺癌风险模型。
虽然先前发表的肺癌 PRS 能够将白人参与者分层为不同的风险水平，但该模型在黑人中没有预测能力。我们的研究结果强调了开发和验证特定种族的肺癌风险模型的必要性。
