Genetic variability in LMP2 and LMP7 is associated with the risk of esophageal squamous cell carcinoma in the Kazakh population but is not associated with HPV infection

• Published in: PloS one 2017-10, Vol.12 (10), p.e0186319-e0186319
• Main Authors: Yang, Lan, Ji, Yu, Chen, Ling, Li, Mei, Wu, Fei, Hu, Jianming, Jiang, Jinfang, Cui, Xiaobin, Chen, Yunzhao, Pang, Lijuan, Wei, Yutao, Li, Feng
• Format: Article
• Language: English
• Subjects: Alphapapillomavirus - pathogenicity; Antigens; Biology and Life Sciences; Cancer therapies; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Case-Control Studies; China; Complications and side effects; Cysteine Endopeptidases - genetics; Cytokines; Cytotoxicity; Deoxyribonucleic acid; Development and progression; DNA; Esophageal cancer; Esophageal carcinoma; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophageal Neoplasms - virology; Esophageal Squamous Cell Carcinoma; Esophagus; Ethnic Groups; Etiology; Female; Gene expression; Gene polymorphism; Genetic aspects; Genetic Predisposition to Disease; Genetic variability; Genotypes; Genotyping; Haplotypes; Health aspects; Hospitals; Human papillomavirus; Humans; Infections; Laboratories; Linkage Disequilibrium; LMP7 gene; Lymphocytes; Male; Medical research; Medicine; Medicine and Health Sciences; Middle Aged; Mortality; Ovarian cancer; Papillomavirus infections; Paraffin; Pathology; Patients; People and Places; Peripheral blood; Physiological aspects; Polymerase chain reaction; Polymorphism; Polymorphism, Single Nucleotide; Population; Proteasome Endopeptidase Complex - genetics; Research and Analysis Methods; Restriction fragment length polymorphism; Risk factors; Risk reduction; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Squamous cell carcinoma; Studies; Variability; Viral infections
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0186319

The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076-2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168-3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286-0.621, p = 8.83×10-6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC.