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

• Published in: International journal of cancer 2019-11, Vol.145 (9), p.2372-2382
• Main Authors: Chen, Hongyan, Chen, Gong, Li, Gang, Zhang, Shuo, Chen, Haitao, Chen, Yuanyuan, Duggan, Dave, Hu, Zhibin, Chen, Juxing, Zhao, Yingjie, Zhao, Yao, Huang, Huiling, Zheng, S. Lilly, Trent, Jeffrey M., Yu, Long, Jiang, Deke, Mo, Zengnan, Wang, Hongwei, Mou, Yonggao, Jiang, Tao, Mao, Ying, Xu, Jianfeng, Lu, Daru
• Format: Article
• Language: English
• Subjects: Brain cancer; Brain Neoplasms - ethnology; Brain Neoplasms - genetics; Brain tumors; Cancer; Case-Control Studies; China - ethnology; Chromosome 12; Europe - ethnology; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genome-wide association studies; Genome-Wide Association Study; Genomes; Glioma; Glioma - ethnology; Glioma - genetics; GWAS; Heterogeneity; Humans; Male; Medical research; oncogene; Polymorphism, Single Nucleotide; Protein-Serine-Threonine Kinases - genetics; rab27 GTP-Binding Proteins - genetics; RAB27A; STK38L
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32179

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, pmeta = 2.33x10‐12, STK38L) as well as a promising association at 15q15‐21.1 (rs4774756, pmeta = 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. What's new? While very few brain tumors are attributed to familial risk factors, the previous identification of inherited genetic variants linked to glioma has raised new questions about the impact of genetics on brain tumor risk. In this genome‐wide association study in a Han Chinese population, two independent genetic variants, one on chromosome 12p11.23 and the second on 15q15‐21.1, were found to be significantly associated with glioma risk. In addition, two risk‐associated variants previously reported in other ancestry groups were also associated with glioma risk in Han Chinese patients. The findings may help advance understanding of genetic susceptibility to glioma.