Abstract
Associations between single nucleotide polymorphisms (SNPs) at 5p15 (TERT-CLPTM1L) and multiple cancer types have been reported. We examined whether polymorphisms in the TERT-CLPTM1L locus were related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. In the first stage, 26 tag SNPs were genotyped in a Guangxi population (855 patients and 1036 controls). In the second stage, the SNPs, which showed significant association, were further genotyped in a Guangdong population (997 patients and 972 controls). Functional analyses were conducted to verify the biological relevance of the associated polymorphism. In the 1st stage, four SNPs (rs2736098, rs2735845, rs402710, and rs401681) were significantly associated with the risk of developing NPC. After the 2nd stage validation, rs2735845 and rs401681 were independently associated with the risk of developing NPC in the additive model (rs2735845, OR = 1.19, 95% CI = 1.04-1.37, P = 0.011; rs401681, OR = 0.85, 95% CI = 0.74-0.99, P = 0.034). Furthermore, we observed higher CLPTM1L messenger RNA levels in fetal mesenchymal stem cells from the rs2735845 G allele carriers compared with that from non-carriers. In addition, using an immunohistochemistry assay, we observed higher TERT and CLPTM1L levels in NPC tissues compared with that in non-cancerous nasopharyngeal tissues. Our findings suggest that polymorphisms in the TERT-CLPTM1L locus may play a role in mediating the susceptibility to NPC in Chinese populations.
Highlights
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck
We investigated the associations of 26 tag SNPs in the telomerase reverse transcriptase (TERT)-CLPTM1L locus on 5p15.33 with the risk of occurrence and progression of NPC in populations in southern China
We found that the expression of TERT and CLPTM1L was higher in the NPC tissues compared to the non-cancer nasopharyngeal tissues
Summary
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck. The incidence of NPC is higher in Southeast Asia and Africa but lower among Caucasians in North America and Europe. In southern China, the incidence rate is approximately 15–50 per 100,000 person-years, which is 100-fold higher than that in the Western world [1]. NPC is a complex disease caused by an interaction among Epstein-Barr virus infection, environmental risk factors and host genes in a multistep process of carcinogenesis [2]. The identification of susceptibility genes contributing to NPC may help clarify the pathogenesis of carcinogenesis and improve the prevention and treatment of this malignancy. The human 5p15.33 locus contains two wellknown genes, the telomerase reverse transcriptase (TERT) and the cleft lip and palate transmembrane www.impactjournals.com/oncotarget
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