Abstract:
:Two genome-wide association studies (GWAS) have identified 5p15.33 (TERT-CLPTM1L) as one of the susceptible regions for glioma in European background. A replication research of our group highlighted the association signals in the TERT gene of this region in a Chinese Han population. To comprehensively explore the region of glioma association at 5p15.33 and to refine the potential causal variants to a smaller critical region, we conducted a fine-mapping association study among 983 cases and 1,024 controls in a Chinese Han population. Using Hapmap3 datasets as a reference, we genotyped 16 tag SNPs across this 87.9-kb region encompassing TERT. Significant association with glioma risk was observed for rs2853677 [GG vs. GA: adjusted OR = 1.46, p = 5.51 × 10(-6), GG vs. AA: adjusted OR = 1.72, p = 7.64 × 10(-6), GG vs. GA and AA: adjusted OR = 1.96, p = 6.8 × 10(-6)] in TERT and an uncommon CLPTM1L haplotype G-T-A of rs4635969, rs6554759 and rs414965 (haplotype frequency = 0.07) was associated with higher glioma risk compared with the most common G-C-G haplotype (adjusted OR = 1.44, simulated p = 6.00 × 10(-3) under additive model). Our results indicate that sequence variants in the region flanking rs2853677 may account for the GWAS and replication signals identified in 5p15.33 for glioma susceptibility in Chinese population; besides, haplotype G-T-A in CLPTM1L also confers a risk to glioma suggesting CLPTM1L is also involved in the etiology of glioma. Additional studies especially those taking advantage of sequencing platforms are warranted to further confirm the conclusions and go deeper with our findings.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Zhao Y,Chen G,Zhao Y,Song X,Chen H,Mao Y,Lu Ddoi
10.1002/ijc.27417subject
Has Abstractpub_date
2012-10-01 00:00:00pages
1569-76issue
7eissn
0020-7136issn
1097-0215journal_volume
131pub_type
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