Genetic associations of leisure sedentary behaviors and the risk of 15 site-specific cancers: A Mendelian randomization study

Jinwei Chen; Kaibin Yang; Youyu Qiu; Weijie Lai; Sifan Qi; Gaoyuan Wang; Lin Chen; Kunpeng Li; Dan Zhou; Qing Liu; Linglong Tang; Xu Liu; Xiaojing Du; Rui Guo; Jun Ma

doi:10.1002/cam4.5974

Genetic associations of leisure sedentary behaviors and the risk of 15 site-specific cancers: A Mendelian randomization study

Cancer Med. 2023 Jun;12(12):13623-13636. doi: 10.1002/cam4.5974. Epub 2023 May 6.

Authors

Jinwei Chen^{1

2}, Kaibin Yang¹, Youyu Qiu^{1

3}, Weijie Lai², Sifan Qi², Gaoyuan Wang¹, Lin Chen¹, Kunpeng Li¹, Dan Zhou¹, Qing Liu⁴, Linglong Tang¹, Xu Liu¹, Xiaojing Du¹, Rui Guo¹, Jun Ma¹

Affiliations

¹ Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, P. R. China.
² Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P. R. China.
³ Department of Radiation Oncology, Sixth Affiliated Hospital, Kunming Medical University, Yuxi, Yunan, China.
⁴ Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, P. R. China.

Abstract

Background and aims: Leisure sedentary behavior (LSB) is associated with the risk of cancer, but the causal relationship between them has not been clarified. The aim of this study was to assess the potential causal association between LSB and risk of 15 site-specific cancers.

Methods: The causal association between LSB and cancer were assessed with univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR). 194 SNPs associated with LSB (from the UK Biobank 408,815 individuals) were adopted as the instrument variables. Sensitivity analyses were performed to ensure the robustness of the results.

Results: UVMR analysis revealed that television watching significantly increased the risk of endometrial cancer (OR = 1.29, 95% CI = 1.02-1.64, p = 0.04) (mainly the endometrioid histology [OR = 1.28, 95% CI = 1.02-1.60, p = 0.031])，breast cancer (OR = 1.16, 95% CI = 1.04-1.30, p = 0.007) (both ER+ breast cancer [OR = 1.17, 95% CI = 1.03-1.33, p = 0.015], and ER- breast cancer [OR = 1.55, 95% CI = 1.26-1.89, p = 2.23 × 10^-5 ]). Although causal association was not found between television watching and ovarian cancer, it was seen in low grade and low malignant potential serous ovarian cancer (OR = 1.49, 95% CI = 1.07-2.08, p = 0.018). However, significant results were not obtained in the UVMR analysis between driving, computer use and the 15 types of cancer. Further MVMR analysis indicated that the above results are independent from most metabolic factors and dietary habits, but mediated by educational attainment.

Conclusion: LSB in form of television watching has independent causal association with the risk of endometrial cancer, breast cancer, and ovarian cancer.

Keywords: cancer risk factors; epidemiology and prevention; genome-wide association; women's cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / etiology
Breast Neoplasms* / genetics
Endometrial Neoplasms* / etiology
Endometrial Neoplasms* / genetics
Female
Genome-Wide Association Study
Humans
Leisure Activities
Mendelian Randomization Analysis / methods
Ovarian Neoplasms* / genetics
Polymorphism, Single Nucleotide
Risk Factors
Sedentary Behavior