Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.

Background: There are well-documented disparities in lung cancer outcomes across populations. Lung cancer screening (LCS) has the potential to reduce lung cancer mortality, but for this benefit to be realized by all high-risk groups, there must be careful attention to ensuring equitable access to this lifesaving preventive health measure. Objectives: To outline current knowledge on disparities in eligibility criteria for, access to, and implementation of LCS, and to develop an official American Thoracic Society statement to propose strategies to optimize current screening guidelines and resource allocation for equitable LCS implementation and dissemination. Methods: A multidisciplinary panel with expertise in LCS, implementation science, primary care, pulmonology, health behavior, smoking cessation, epidemiology, and disparities research was convened. Participants reviewed available literature on historical disparities in cancer screening and emerging evidence of disparities in LCS. Results: Existing LCS guidelines do not consider racial, ethnic, socioeconomic, and sex-based differences in smoking behaviors or lung cancer risk. Multiple barriers, including access to screening and cost, further contribute to the inequities in implementation and dissemination of LCS. Conclusions: This statement identifies the impact of LCS eligibility criteria on vulnerable populations who are at increased risk of lung cancer but do not meet eligibility criteria for screening, as well as multiple barriers that contribute to disparities in LCS implementation. Strategies to improve the selection and dissemination of LCS in vulnerable groups are described.

Landmark results from the National Lung Screening Trial (NLST) support recommendations for lung cancer screening (LCS) with low-dose computed tomography (LDCT) in the United States.^1-3 The NLST demonstrated that annual screening of high-risk adults with LDCT (vs chest radiography) led to a 20% reduction in lung cancer mortality.⁴ The Dutch-Belgian NELSON (Nederlands-Leuvens Longkanker Screenings Onderzoek) trial subsequently showed a mortality benefit from LDCT screening,⁵ substantiating LCS as an effective strategy to reduce the high mortality rate of lung cancer worldwide. Since the publication of the 2013 United States Preventive Services Task Force (USPSTF) and Centers for Medicare & Medicaid Services recommendations, which endorse annual LDCT screening of adults aged 55 to 77 years or 80 years with a smoking history of 30 or more pack-years and less than 15 years since quitting, the uptake of LCS has been increasing nationally.^6-9 However, for LCS to achieve similar long-term effectiveness in real-world practice, successful completion of multiple steps, including individuals returning for annual LDCT screening, is vital.¹⁰