Association Between Telomere Length and Risk of Lung Cancer in an Asian Population: A Mendelian Randomization Study

Yi Teng; Dan Qi Huang; Rui Xi Li; Chao Yi; Yi Qiang Zhan

doi:10.14740/wjon1624

Association Between Telomere Length and Risk of Lung Cancer in an Asian Population: A Mendelian Randomization Study

World J Oncol. 2023 Aug;14(4):277-284. doi: 10.14740/wjon1624. Epub 2023 Aug 4.

Authors

Yi Teng^{1

2

3}, Dan Qi Huang^{1

2

3}, Rui Xi Li^{4

3}, Chao Yi⁵, Yi Qiang Zhan^{1

6}

Affiliations

¹ Department of Epidemiology, School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, China.
² National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ These authors contributed equally to this work.
⁴ Department of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, China.
⁵ Guangming Center for Disease Control and Prevention, Shenzhen, China.
⁶ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Abstract

Background: Several traditional observational studies and Mendelian randomization (MR) studies have indicated an association between leukocyte telomere length (LTL) and the risk of lung cancer in the European population. However, the results in the Asian population are still unclear. The objective was to reveal the genetic causal association between LTL and the risk of lung cancer in the Asian population.

Methods: We conducted a two-sample MR analysis using summary statistics. Instrumental variables (IVs) were obtained from the genome-wide association studies (GWAS) of LTL (n = 23,096) and lung cancer (n = 212,453) of Asian ancestry. We applied the random-effects inverse-variance weighted (IVW) model as the main method. As well, several other models were performed as complementary methods to assess the impact of potential MR assumption violations, including MR-Egger regression, weighted median, and weighted mode models.

Results: We included eight single-nucleotide polymorphisms (SNPs) as IVs for LTL and found that LTL was significantly associated with the risk of lung cancer in the IVW model (odds ratio (OR): 1.60; 95% confidence interval (CI): 1.31 - 1.97; P = 5.96 × 10^-6), which was in line with the results in the weighted median and weighted mode models. However, the relationship was not statistically significant in the MR-Egger regression model (OR: 1.44; 95% CI: 0.92 - 2.26; P = 0.160). Sensitivity analyses indicated the robustness of the results.

Conclusions: This two-sample MR study confirmed that longer telomere length significantly increased the risk of lung cancer in the Asian population, which was in accord with findings in the Western population.

Keywords: Lung cancer; Mendelian randomization; Telomere length.