Two novel genetic variants in the STK38L and RAB27A genes are associated with glioma susceptibility

Hongyan Chen; Gong Chen; Gang Li; Shuo Zhang; Haitao Chen; Yuanyuan Chen; Dave Duggan; Zhibin Hu; Juxing Chen; Yingjie Zhao; Yao Zhao; Huiling Huang; S Lilly Zheng; Jeffrey M Trent; Long Yu; Deke Jiang; Zengnan Mo; Hongwei Wang; Yonggao Mou; Tao Jiang; Ying Mao; Jianfeng Xu; Daru Lu

doi:10.1002/ijc.32179

Two novel genetic variants in the STK38L and RAB27A genes are associated with glioma susceptibility

Int J Cancer. 2019 Nov 1;145(9):2372-2382. doi: 10.1002/ijc.32179. Epub 2019 Mar 18.

Authors

Hongyan Chen¹, Gong Chen², Gang Li³, Shuo Zhang^{1

4}, Haitao Chen^{1

5}, Yuanyuan Chen¹, Dave Duggan⁶, Zhibin Hu⁷, Juxing Chen⁸, Yingjie Zhao¹, Yao Zhao², Huiling Huang⁹, S Lilly Zheng¹⁰, Jeffrey M Trent⁶, Long Yu¹, Deke Jiang^{1

5}, Zengnan Mo¹¹, Hongwei Wang¹², Yonggao Mou¹³, Tao Jiang¹⁴, Ying Mao², Jianfeng Xu^{1

10}, Daru Lu¹

Affiliations

¹ State Key Laboratory of Genetic Engineering, Zhongshan Hospital, Fudan University, and School of Life Sciences, Fudan University, Shanghai, China.
² Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
³ Department of Neurosurgery, Tangdu hospital, the Fourth Military Medical University, Xi'an, China.
⁴ Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
⁵ State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, GuangZhou, China.
⁶ Translational Genomics Research Institute (TGen), Phoenix, AZ.
⁷ Department of Epidemiology, Center for Global Health, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
⁸ Department of Neurosurgery, Shanghai Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
⁹ Department of Neuroscience, Tianjin Huanhu Hospital, Tianjin, China.
¹⁰ Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, IL.
¹¹ Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China.
¹² Department of Medicine, The University of Chicago, Chicago, IL.
¹³ Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
¹⁴ Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

PMID: 30714141
DOI: 10.1002/ijc.32179

Abstract

Glioma is the most common malignant primary brain tumors with poor prognosis. Genome wide association studies (GWAS) of glioma in populations with Western European ancestry were completed in the US and UK. However, our previous results strongly suggest the genetic heterogeneity could be important in glioma risk. To systematically investigate glioma risk-associated variants in Chinese population, we performed a multistage GWAS of glioma in the Han Chinese population, with a total of 3,097 glioma cases and 4,362 controls. In addition to confirming two associations reported in other ancestry groups, this study identified one new risk-associated locus for glioma on chromosome 12p11.23 (rs10842893, p_meta = 2.33x10-12, STK38L) as well as a promising association at 15q15-21.1 (rs4774756, p_meta = 6.12x10-8, RAB27A) in 3,097 glioma cases and 4,362 controls. Our findings demonstrate two novel association between the glioma risk region marked by variant rs10842893 and rs4774756) and glioma risk. These findings may advance the understanding of genetic susceptibility to glioma.

Keywords: GWAS; RAB27A; STK38L; glioma; oncogene.

Publication types

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

MeSH terms

Brain Neoplasms / ethnology
Brain Neoplasms / genetics*
Case-Control Studies
China / ethnology
Europe / ethnology
Genetic Predisposition to Disease
Genome-Wide Association Study
Glioma / ethnology
Glioma / genetics*
Humans
Male
Polymorphism, Single Nucleotide*
Protein Serine-Threonine Kinases / genetics*
rab27 GTP-Binding Proteins / genetics*

Substances

rab27 GTP-Binding Proteins
Protein Serine-Threonine Kinases
STK38L protein, human
RAB27A protein, human