越来越多的证据表明当地环境暴露对癌症易感性的影响。尽管如此，一些协会仍然存在争议。此外，我们对当地环境与遗传变异之间可能存在的相互作用的了解仍然非常有限。本研究的目的是阐明当地环境的作用及其与遗传学对常见癌症发展的可能相互作用。使用英国生物银行(UKBB) 前瞻性队列中，我们选择了 12 种当地环境暴露：氮氧化物、二氧化氮、颗粒物（10 和 2.5μm）、噪音污染、城市交通、距海岸的居住距离、绿地百分比、自然环境、水和各参赛者居住坐标1000m以内的国内花园。对总共 53,270 例病例和 302,645 名对照者测试了所有这些暴露与 17 种不同类型癌症的关联。此外，还计算了每种癌症的多基因评分（PGS），以测试可能的基因-环境相互作用。最后，进行中介分析。考虑到多重测试，观察到 36 个具有统计学显着性的关联（p<2.19×10-4）。在这些新的关联中，我们观察到居住在离海岸较远的个体患前列腺癌的风险较高（OR=1.13，CI95%=1.06-1.20，P=1.98×10-4）。这种关联部分是由体力活动（间接效应（IE）=-8.48×10-7）和户外活动时间（IE=9.07×10-6）介导的。所有 PGS 均显示出统计学上显着的关联。最后，基因组-环境相互作用分析表明，当地环境和遗传变异独立影响癌症风险。靠近海岸居住和空气污染分别与前列腺癌和皮肤黑色素瘤风险降低相关。 UKBB 的这些发现支持当地环境对癌症发展的作用，这种作用独立于遗传学，并且可能由多种生活方式因素介导。版权所有 © 2023。由 Elsevier Inc. 出版。

There is a growing body of evidence on the effect of the local environment exposure on cancer susceptibility. Nonetheless, several of the associations remain controversial. Moreover, our understanding of the possible interaction between the local environment and the genetic variability is still very limited.The aim of this study was to clarify the role of the local environment and its possible interplay with genetics on common cancers development.Using the UK Biobank (UKBB) prospective cohort, we selected 12 local environment exposures: nitrogen oxides, nitrogen dioxides, particulate matter (10 and 2.5  μm), noise pollution, urban traffic, living distance from the coast, percentage of greenspace, natural environment, water, and domestic garden within 1000 m from the residential coordinates of each participant. All these exposures were tested for association with 17 different types of cancer for a total of 53,270 cases and 302,645 controls. Additionally, a polygenic score (PGS) was computed for each cancer, to test possible gene-environment interactions. Finally, mediation analyses were carried out.Thirty-six statistically significant associations considering multiple testing (p < 2.19 × 10-4) were observed. Among the novel associations we observed that individuals living farther from the coast had a higher risk of developing prostate cancer (OR = 1.13, CI95% = 1.06-1.20, P = 1.98 × 10-4). This association was partially mediated by physical activity (indirect effect (IE) = -8.48 × 10-7) and the time spent outdoor (IE = 9.07 × 10-6). All PGSs showed statistically significant associations. Finally, genome-environment interaction analysis showed that local environment and genetic variability affect cancer risk independently.Living close to the coast and air pollution were associated with a decreased risk of prostate cancer and skin melanoma, respectively. These findings from the UKBB support the role of the local environment on cancer development, which is independent from genetics and may be mediated by several lifestyle factors.Copyright © 2023. Published by Elsevier Inc.