OBJECTIVE: We aimed to evaluate independent and joint associations of CVH and polygenic risk score (PRS) with risks of overall and site-specific cancers.
METHODS: We undertook a population-based cohort study based on the UK Biobank. The CVH score was constructed by physical activity, body mass index, nicotine exposure, sleep, diet, blood pressure, lipid profile, and blood glucose. PRSs were assessed individually for 18 cancer types by their independent single-nucleotide polymorphisms previously identified in genome-wide association studies. Multivariable Cox proportional-hazards models were applied to explore the independent and joint associations of CVH and PRS with cancer incidence risk. The results were displayed as hazard ratio (HR) and 95% confidence interval (CI).
RESULTS: Compared with low CVH, high CVH was associated with decreased risks of overall cancer and the majority of common cancers, including digestive system [HRs (95% CI): 0.33 (0.23, 0.45)-0.66 (0.58, 0.75)], lung (HR: 0.25; 95% CI: 0.21, 0.31), renal (HR: 0.42; 95% CI: 0.32, 0.56), bladder (HR: 0.55; 95% CI: 0.44, 0.69), breast (HR: 0.83; 95% CI: 0.74, 0.92), and endometrial cancers (HR: 0.39; 95% CI: 0.30, 0.51). For overall cancer in males, there was an interaction between CVH and PRS. Notably, individuals with high CVH across all levels of PRS had lower risks of overall cancer for females and 8 site-specific cancers than those with low CVH and high PRS [HRs (95% CIs): 0.18 (0.12, 0.25)-0.79 (0.71, 0.87)].
CONCLUSIONS: High CVH was related to decreased risks of overall cancer and multiple cancers regardless of genetic predispositions. Our findings underscored the value of improving CVH for cancer prevention in the general population.
目的:我们旨在评估CVH和多基因风险评分(PRS)与整体和特定部位癌症风险的独立和联合关联。
方法:我们基于UKBiobank进行了一项基于人群的队列研究。CVH评分是通过体力活动构建的,身体质量指数,尼古丁暴露,睡眠,饮食,血压,血脂谱,和血糖。通过先前在全基因组关联研究中报道的独立单核苷酸多态性,对18种癌症类型的PRS进行了单独评估。应用多变量Cox比例风险模型来探讨CVH和PRS与癌症发生风险的独立和联合关联。结果显示为风险比(HR)和95%置信区间(CI)。
结果:与低CVH相比,高CVH与总体癌症和大多数常见癌症的风险降低相关,包括消化系统[HR(95%CI):0.33(0.23,0.45)-0.66(0.58,0.75)],肺[HR(95%CI):0.25(0.21,0.31)],肾[HR(95%CI):0.42(0.32,0.56)],膀胱[HR(95%CI):0.55(0.44,0.69)],乳腺癌[HR(95%CI):0.83(0.74,0.92)]和子宫内膜癌[HR(95%CI):0.39(0.30,0.51)]。对于男性的整体癌症,CVH和PRS之间存在相互作用。值得注意的是,在所有水平的PRS中,与低CVH和高PRS患者相比,高CVH患者的女性和8种部位特异性癌症患者的总体癌症风险较低[HRs(95CIs):0.18(0.12,0.25)-0.79(0.71,0.87)].
结论:高CVH与总体癌症和多种癌症的风险降低有关,无论遗传易感性如何。我们的发现强调了改善CVH对普通人群癌症预防的价值。