Evaluation of human leukocyte antigen-A (HLA-A), other non-HLA markers on chromosome 6p21 and risk of nasopharyngeal carcinoma

The association between human leukocyte antigen (HLA) genes (located in the Major Histocompatibility Complex [MHC] region of chromosome 6p21) and NPC has been known for some time. Recently, two genome-wide association studies (GWAS) conducted in Taiwan and China confirmed that the strongest evidence...

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Published in:	PloS one 2012-08, Vol.7 (8), p.e42767-e42767
Main Authors:	Hsu, Wan-Lun, Tse, Ka-Po, Liang, Sharon, Chien, Yin-Chu, Su, Wen-Hui, Yu, Kelly J, Cheng, Yu-Juen, Tsang, Ngan-Ming, Hsu, Mow-Ming, Chang, Kai-Ping, Chen, I-How, Chen, Tzu-I, Yang, Czau-Siung, Goldstein, Alisa M, Chen, Chien-Jen, Chang, Yu-Sun, Hildesheim, Allan
Format:	Article
Language:	eng
Subjects:	Alleles Antigens Biology Cancer Cancer genetics Carcinoma Chromosome 6 Chromosomes Chromosomes, Human, Pair 6 - genetics Confidence Intervals Consent Epidemiology Evaluation Exons Genes Genetic aspects Genetic Markers Genetic Predisposition to Disease Genetics Genome-wide association studies Genome-Wide Association Study Genomes Genomics Genotyping Haplotypes Haplotypes - genetics Health care Histocompatibility antigen HLA Histocompatibility antigens HLA antigens HLA histocompatibility antigens HLA-A Antigens - genetics Homogeneity Hospitals Humans Leukocytes Major histocompatibility complex Medical screening Medicine Middle Aged Nasopharyngeal Carcinoma Nasopharyngeal Neoplasms - genetics Odds Ratio Otolaryngology Preventive medicine Public health Risk analysis Risk Factors Single-nucleotide polymorphism Statistical analysis Studies Taiwan Throat cancer White blood cells
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Summary:	The association between human leukocyte antigen (HLA) genes (located in the Major Histocompatibility Complex [MHC] region of chromosome 6p21) and NPC has been known for some time. Recently, two genome-wide association studies (GWAS) conducted in Taiwan and China confirmed that the strongest evidence for NPC association was mapped to the MHC region. It is still unclear, however, whether these findings reflect direct associations with Human Leukocyte Antigen (HLA) genes and/or to other genes in this gene-rich region. To better understand genetic associations for NPC within the MHC region of chromosome 6, we conducted an evaluation that pooled two previously conducted NPC case-control studies in Taiwan (N = 591 cases and N = 521 controls). PCR-based genotyping was performed for 12 significant SNPs identified within 6p21 in the Taiwan NPC GWAS and for the HLA-A gene (exons 2 and 3). After confirming homogeneity between the two studies, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. We found that HLA-A (p-trend = 0.0006) and rs29232 (within the GABBR1 gene; p-trend = 0.005) were independent risk factors for NPC after adjustment for age, gender, study and each other. NPC risk was highest among individuals who were homozygous for the HLA-A*0207 risk allele and carriers of the rs29232 risk allele (A). Our study suggests that most of the SNPs significantly associated with NPC from GWAS reflect previously identified HLA-A associations. An independent effect of rs29232 (GABBR1), however, remained, suggesting that additional genes within this region might be associated with NPC risk.
ISSN:	1932-6203 1932-6203