Polymorphisms of HLA-A and HLA-B genes in genetic susceptibility to esophageal carcinoma in Chaoshan Han Chinese.

Esophageal carcinoma (EC) occurs at high rate in Chaoshan region of southern China. Human leukocyte antigen (HLA) polymorphism has been implicated in risk for various cancers. To investigate the impact of HLA-A and HLA-B polymorphisms on susceptibility to EC, a case-control study was conducted among 206 patients with esophageal squamous cell carcinoma and 524 controls from Chaoshan Han population. HLA-A and HLA-B polymorphisms were genotyped by polymerase chain reaction-sequence-specific primers. Genotypic association tests for dominant, recessive, and additive models, and haplotypic association were calculated using unconditional logistic regression. A*11 was identified in a recessive model as an only allele strongly associated with EC risk (odds ratios [OR]=2.10, 95% confidence interval [CI]=1.33-3.31) even after correction for multiple test. The haplotypes A*02-B*46 (OR=1.53, 95% CI=1.04-2.24) and A*11-B*51 (OR=2.29, 95% CI=1.20-4.40) showed association with increased risk for EC, whereas A*11-B*58 (OR=0.00, 95% CI=0.00-0.82) was associated with decreased risk, though the significance of these haplotypes was lost after correction. This is a first association study at genetic level identifying HLA-A and HLA-B-related variations in genetic susceptibility to EC among Chaoshan population. The variation pattern is likely to be EC-specific because it is different from that observed for nasopharyngeal carcinoma in the same study population and might, at least in part, explain the high rate of EC in this ethnic group.

Genetic link between Chaoshan and other Chinese Han populations: Evidence from HLA-A and HLA-B allele frequency distribution.

The genetic polymorphism of HLA-A and HLA-B loci was investigated in 505 Chaoshanese using PCR-SSP method. Among the HLA-A alleles detected, A*11 (35.64%) was most frequent, followed by A*02 (31.78%). Of 34 HLA-B alleles tested, 30 were observed, in which B*60 (21.68%), B*46 (14.46%), and B*58 (10.69%) were highly predominant. Comparison was made with other nine Chinese Han ethnic groups covering the Mainland China, Taiwan, Hong Kong, and Singapore. The high frequent alleles found in Chaoshanese were also common in other Chinese groups compared though the frequency levels varied from group to group. The phylogenic tree analysis based on the HLA-A and -B allele frequencies of all the 10 Chinese ethnic groups revealed that Chaoshanese, while clustering in general with the southern China-related Han Chinese, had the highest affinity to the Mainland Minnanese, but separated distinctively from the northern Han Chinese. The study, however, was yet to confirm the hypothesis of the Central Plains Han origin of Chaoshanese. Interestingly, the alleles (B*46, B*38, and B*58) and the related haplotypes (A*02-B*46 and A*33-B*58) that are positively associated with nasopharyngeal carcinoma (NPC), a disease prevailing predominantly among southern Chinese, were always at much higher frequencies among southern Chinese than among northern Chinese, whereas A*31 and B*13, the two alleles with highly protective effects for NPC, and the associated haplotype A*30-B*13 were predominantly high in northern Chinese. The different genetic background between northern and southern China may explain, at least partially, the prevalence of NPC among southern Chinese.