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. 2015 Jul 25;34(1):70.
doi: 10.1186/s13046-015-0185-y.

Heterozygote of TAP1 Codon637 decreases susceptibility to HPV infection but increases susceptibility to esophageal cancer among the Kazakh populations

Ningjing Zou  1 , Lan Yang  2 , Ling Chen  3 , Tingting Li  4 , Tingting Jin  5 , Hao Peng  6 , Shumao Zhang  7 , Dandan Wang  8 , Ranran Li  9 , Chunxia Liu  10 , Jinfang Jiang  11 , Lianghai Wang  12 , Weihua Liang  13 , Jianming Hu  14 , Shugang Li  15 , Chuanyue Wu  16   17 , Xiaobin Cui  18   19 , Yunzhao Chen  20   21 , Feng Li  22   23
Affiliations

Heterozygote of TAP1 Codon637 decreases susceptibility to HPV infection but increases susceptibility to esophageal cancer among the Kazakh populations

Ningjing Zou et al. J Exp Clin Cancer Res. .

Abstract

Background: The role of human papillomavirus (HPV) may be involved in the development of esophageal cancer (EC) and the polymorphic immune response gene transporter associated with antigen processing (TAP) may be involved in HPV persistence and subsequent cancer carcinogenesis. The current study aims to provide association evidence for HPV with EC, to investigate TAP1 polymorphisms in EC and assess its association with HPV statuses and EC in Kazakhs.

Methods: The HPV genotypes in 361 patients with EC and 66 controls selected from Kazakh population were evaluated using PCR. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to detect two SNPs of TAP1 in 150 cases comprised of 75 HPV(+) and 75 HPV(-) patients and 283 pure ethnic population of Kazakh and evaluate their associations with susceptibility to EC. A case-to-case comparison based on the genotyping results was conducted to address the function of TAP1 variants in the involvement of HPV.

Results: The presence of four HPV genotypes in EC tissues - including HPV 16, 18, 31, 45 - was significantly higher at 64.6 % than those in controls at 18.2 % (P < 0.001). Such presence was strongly associated with increased risk of EC (OR 8.196; 95 % CI 4.280-15.964). The infection of HPV16, and multi-infection of 16 and 18 significantly increase the risk for developing EC (OR 4.616, 95 % CI 2.099-10.151; and OR 6.029, 95 % CI 1.395-26.057 respectively). Heterozygote of TAP1 D637G had a significantly higher risk for developing EC (OR 1.626; 95 % CI 1.080-2.449). The odds ratio for HPV infection was significantly lower among carriers of TAP1 D637G polymorphism (OR 0.281; 95 % CI 0.144-0.551).

Conclusions: HPV infection exhibits a strong positive association with the risk of EC in Kazakhs. Heterozygote of TAP1 D637G decreases susceptibility to HPV infection in patients with EC but increases susceptibility to EC among the Kazakh populations.

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Figures

Fig. 1
Fig. 1
Electrophoretic analysis of the HPV genotyping using PCR. (a) GP5+/GP6+ PCR. Lane 1, 2, 4, 6 and 7 in HPV infection (150 bp); Lane 3 and 4 without HPV infection; Lane 8, negative control; Lane 9, positive control; Lane 10, blank control; M, molecular weight marker. (b) Human papillomavirus PCR results. Lane 1, 3, 5 and 6 in HPV16 infection (150 bp); Lane 2, 4 and 7 without HPV16 infection; Lane 8, negative control; Lane 9, positive control; Lane 10, blank control; M, molecular weight marker
Fig. 2
Fig. 2
Sequencing map of the genotype for the HPV L1 (a) and HPV 16E7 (b)
Fig. 3
Fig. 3
PCR-RFLP assay for analyzing the TAP1 Codon333 and 637 polymorphisms. PCR product was digested by restriction enzyme and visualized in 3 % agarose gel stained with ethidium bromide. (a) The typical genotypes of TAP1 Codon333 A/G. Lane 1: AG genotype (430,274 and 156 bp); lane 2: AA genotype (274 and 156 bp); lane 3: GG genotype (430 bp). (b) The typical genotypes of TAP1 Codon637 A/G. Lane 1: AG genotype (405,260 and 145 bp); lane 2: GG genotype (405 bp); lane 3: AA genotype (260 and 145 bp). M, molecular weight marker
Fig. 4
Fig. 4
Sequencing map of the genotype for the TAP1 Codon333 polymorphism (a) and TAP1 Codon637 polymorphism (b)
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