Population attributable fraction of lung cancer due to genetic variants, modifiable risk factors, and their interactions: a nationwide prospective cohort study

Xiaojie Wang; Zhengmin Min Qian; Zilong Zhang; Miao Cai; Lan Chen; Yinglin Wu; Haitao Li; Echu Liu; Stephen Edward McMillin; Hualiang Lin

doi:10.1016/j.chemosphere.2022.134773

Population attributable fraction of lung cancer due to genetic variants, modifiable risk factors, and their interactions: a nationwide prospective cohort study

Chemosphere. 2022 Aug:301:134773. doi: 10.1016/j.chemosphere.2022.134773. Epub 2022 Apr 29.

Authors

Affiliations

¹ Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
² Department of Epidemiology and Biostatistics, College for Public Health & Social Justice, Saint Louis University, Saint Louis, USA.
³ Department of Social Medicine and Health Service Management, Shenzhen University General Hospital, Shenzhen, China.
⁴ Department of Health Management and Policy, College for Public Health and Social Justice, Saint Louis University, Saint Louis, USA.
⁵ School of Social Work, College for Public Health and Social Justice, Saint Louis University, Saint Louis, USA.
⁶ Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China. Electronic address: linhualiang@mail.sysu.edu.cn.

PMID: 35500626
DOI: 10.1016/j.chemosphere.2022.134773

Abstract

Background: Genetic variants and modifiable risk factors (including environmental exposure and lifestyle) greatly contribute to the development of lung cancer. The population attributable fraction (PAF) of these risk factors, especially their interactive effects, has not been well quantified.

Methods: A total of 398,577 participants were included in this analysis. There were 2504 incident lung cancer cases identified over an average 10.4-year follow-up. We applied Cox proportional hazards models to examine the associations between risk factors and incident lung cancer. We further developed a polygenic risk score and evaluated whether environmental factors modified the effect of genetic risk on incident lung cancer. Furthermore, we calculated the PAF for each risk factor, as well as their gene-environment additive interaction, and then combined them to create a weighted PAF that takes into consideration participants with overlapping risk factors.

Results: Our analysis showed that smoking was the leading risk factor for lung cancer with a PAF of 63.73%. We observed additive interactions between smoking, PM_2.5, NO_x, and genetic risk, with PAFs of 17.85% (smoking-high genetic risk interaction), 10.79% (smoking-intermediate genetic risk interaction), 5.30% (NO_x-high genetic risk interaction), 6.55% (PM_2.5-high genetic risk interaction), and 4.99% (PM_2.5-intermediate genetic risk interaction). We estimated that 73.46% of lung cancer cases could be attributable to potentially modifiable risk factors after adjusting for the correlation between them.

Conclusion: High genetic risk and several modifiable factors may increase the risk of incident lung cancer. Participants with a high genetic risk may be more vulnerable to developing lung cancer if exposed to smoking and/or high air pollution. Our findings provide evidence that the majority of incident lung cancer cases could be prevented by eliminating modifiable risk factors.

Keywords: Additive interaction; Genetic susceptibility; Lung cancer; Modifiable risk factors; Population attributable fractions.

MeSH terms

Air Pollution*
Humans
Lung Neoplasms* / epidemiology
Lung Neoplasms* / genetics
Particulate Matter
Prospective Studies
Risk Factors

Substances

Particulate Matter

Abstract

MeSH terms

Substances

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