Heritable Traits and Lung Cancer Risk: A Two-Sample Mendelian Randomization Study

Authors

Rowland W Pettit
Jinyoung Byun
Younghun Han
Quinn T Ostrom
Cristian Coarfa
Melissa L Bondy
Christopher I Amos

Publication Date

10-2-2023

Journal

Cancer Epidemiology, Biomarkers & Prevention

DOI

10.1158/1055-9965.EPI-22-0698

PMID

37530747

PMCID

PMC10651112

PubMedCentral® Posted Date

4-2-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Humans, Mendelian Randomization Analysis, Lung Neoplasms, Risk, Carcinoma, Non-Small-Cell Lung, Smoking, Genome-Wide Association Study, Polymorphism, Single Nucleotide

Abstract

INTRODUCTION: Lung cancer is a complex polygenic disorder. Analysis with Mendelian randomization (MR) allows for genetically predicted risks to be estimated between exposures and outcomes.

METHODS: We analyzed 345 heritable traits from the United Kingdom Biobank and estimated their associated effects on lung cancer outcomes using two sample MR. In addition to estimating effects with overall lung cancer, adenocarcinoma, small cell lung cancer, and squamous cell lung cancers, we performed conditional effect modeling with multivariate MR (MVMR) and the traits of alcohol use, smoking initiation, average pre-tax income, and educational attainment.

RESULTS: Univariate MR provided evidence for increased age at first sexual intercourse (OR, 0.55; P = 6.15 × 10-13), educational attainment (OR, 0.24; P = 1.07 × 10-19), average household income (OR, 0.58; P = 7.85 × 10-05), and alcohol usually taken with meals (OR, 0.19; P = 1.06 × 10-06) associating with decreased odds of overall lung cancer development. In contrast, a lack of additional educational attainment (OR, 8.00; P = 3.48 × 10-12), body mass index (OR, 1.28; P = 9.00 × 10-08), pack years smoking as a proportion of life span (OR, 9.93; P = 7.96 × 10-12), and weekly beer intake (OR, 3.48; P = 4.08 × 10-07) were associated with an increased risk of overall lung cancer development.

CONCLUSIONS: Many heritable traits associated with an increased or inverse risk of lung cancer development. Effects vary based on histologic subtype and conditional third trait exposures.

IMPACT: We identified several heritable traits and presented their genetically predictable impact on lung cancer development, providing valuable insights for consideration.

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