Research Paper|Volume 13, Issue 9|pp 12456—12465

Age-related differences of genetic susceptibility to patients with acute lymphoblastic leukemia

Qing Hao^1,^2,³, Minyuan Cao⁴, Chunlan Zhang⁵, Dandan Yin⁴, Yuelan Wang⁴, Yuanxin Ye⁴, Shan Zhao⁴, Yunfan Yang⁵, Ke-Ling Chen⁶, Binwu Ying⁴, Lanlan Wang⁴, Yiguan Zhang³, Caigang Xu⁵, Yiping Zhu⁷, Yu Wu⁵, Ju Gao⁷, Jun-Ning Zhao³, Yan Zhang¹, Xiaoxi Lu⁷

¹Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
²College of Pharmaceutical Sciences, Southwest Medical University, Luzhou, China
³Sichuan Center for Translational Medicine of Traditional Chinese Medicine, Institute of Translational Pharmacology, Sichuan Academy of Chinese Medicine Sciences, Chengdu, China
⁴Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
⁵Department of Hematology, West China Hospital, Sichuan University, Chengdu, China
⁶Digestive Surgery Institute, West China Hospital, Sichuan University, Chengdu, China
⁷Department of Hematology/Oncology, West China Second Hospital, Sichuan University, Chengdu, China

* Equal contribution

Received: January 5, 2021Accepted: March 5, 2021Published: April 23, 2021

https://doi.org/10.18632/aging.202903

Copyright: © 2021 Hao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Inherited predispositions to acute lymphoblastic leukemia have been well investigated in pediatric patients, but studies on adults, particularly Chinese patients, are limited. In this study, we conducted a genome-wide association study in 466 all-age Chinese patients with Acute lymphoblastic leukemia (ALL) and 1,466 non-ALL controls to estimate the impact of age on ALL susceptibility in the Chinese population. Among the 17 reported loci, 8 have been validated in pediatric and 1 in adult patients. The strongest association signal was identified at ARID5B locus and gradually decreased with age, while the signal at GATA3 exhibited the opposite trend and significantly impact on adult patients. With genome-wide approaches, germline variants at 2q14.3 rank as the top inherited predisposition to adult patients (e.g., rs73956024, P = 4.3 × 10^-5) and separate the genetic risk of pediatric vs. adult patients (P = 3.6 × 10^-6), whereas variants at 15q25.3 (e.g., rs11638062) have a similar impact on patients in different age groups (overall P = 2.9 × 10^-7). Our analysis highlights the impact of age on genetic susceptibility to ALL in Chinese patients.