Evaluation of Human Leukocyte Antigen-A (HLA-A), Other Non-HLA Markers on Chromosome 6p21 and Risk of Nasopharyngeal Carcinoma
Resource
PLoS One, 7(8)
Journal
PLoS ONE
Pages
e42767
Date Issued
2012
Date
2012
Author(s)
Hsu, Wan-Lun
Tse, Ka-Po
Liang, Sharon
Chien, Yin-Chu
Su, Wen-Hui
Yu, Kelly J.
Cheng, Yu-Juen
Tsang, Ngan-Ming
Chang, Kai-Ping
Chen, I-How
Chen, Tzu-I
Yang, Czau-Siung
Goldstein, Alisa M.
Chen, Chien-Jen
Chang, Yu-Sun
Hildesheim, Allan
Abstract
Background: 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.
Methods: 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).
Findings: 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).
Conclusion: 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.
SDGs
Other Subjects
HLA antigen; human leukocyte antigen A; unclassified drug; adult; age; allele; article; cancer risk; case control study; chromosome 6p; chromosome structure; controlled study; disease association; exon; female; gender; gene; genetic association; genetic predisposition; genetic risk; genotype; HLA A gene; homozygosity; human; major clinical study; major histocompatibility complex; male; nasopharynx carcinoma; polymerase chain reaction; single nucleotide polymorphism; Taiwan; Alleles; Chromosomes, Human, Pair 6; Confidence Intervals; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Haplotypes; HLA-A Antigens; Humans; Middle Aged; Nasopharyngeal Neoplasms; Odds Ratio; Risk Factors; Taiwan
Type
journal article
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