TY - JOUR
T1 - Multiple low-frequency and rare HLA-B allelic variants are associated with reduced risk in 1,105 nasopharyngeal carcinoma patients in Hunan province, southern China
AU - Tian, Wei
AU - Zhu, Fa Ming
AU - Cai, Jin Hong
AU - Li, Li Xin
AU - Jin, He Kun
AU - Wang, Wen Yi
N1 - Funding Information:
We thank all of the blood donors. The authors express their gratitude to the two anonymous reviewers for their valuable comments and suggestions. Assistance of Dr KangLong Liu during sample collection is greatly appreciated. We also thank Fan Wang for his help in the early stage of our study. This work was supported by grants from the Program for New Century Excellent Talents in University (Proj.No.NCET‐08‐0564), National Natural Science Foundation of China (Proj.No.30671915, 30300311), The Outstanding Youth Science Foundation of Hunan Province (Proj.No.04JJ1007) and Central South University (Proj.No.2013JSJJ038) all awarded to W.T.
Publisher Copyright:
© 2020 UICC
PY - 2020/9/1
Y1 - 2020/9/1
N2 - In our study, 1,105 cases of nasopharyngeal carcinoma (NPC) and 1,430 normal controls recruited from Hunan province, southern China were typed for human leukocyte antigen (HLA)-B locus by Sanger sequencing exons 2–4. Besides confirming the NPC association with HLA-B*46:01 allele, HLA-A*02:07-B*46:01 and HLA-A*33:03-B*58:01 haplotypes (all positive), and HLA-B*13 lineage (negative), all of which were relatively common, strong negative associations were observed for five low-frequency and rare alleles or lineages, including HLA-B*07, -B*27:04, -B*39, -B*51:02 and -B*55:02, with odds ratio (OR) ranging from 0.16 to 0.3 (all pcorrected < 0.05). These strong protective associations were independent of linkage disequilibrium (LD) between HLA-A and HLA-B loci. Further analysis indicated a single amino acid change from histidine to tyrosine at residue 171 is probably crucial for the mutant allele, HLA-B*51:02, to mediate resistance to NPC. A subset of NPC cases (n = 821) and normal controls (n = 1,035) were tested for antivirus capsid antigen immunoglobulin A (anti-VCA IgA), which differed drastically between the two groups [67.7% vs. 5.5%, OR (95% confidence interval) = 36 (26.55–48.81), p < 0.0001]. HLA-B allelic variation did not associate with seropositivity for anti-VCA IgA in either group. Results from our study show, more clearly than previously, the existence of a cluster of low-frequency and rare HLA-B variants conferring low, or very low risk to NPC, a phenomenon not observed in other ethnic groups. Our data shed new insights into genetic susceptibility to NPC in southern Chinese populations. Future independent studies are warranted to replicate the findings reported in our study.
AB - In our study, 1,105 cases of nasopharyngeal carcinoma (NPC) and 1,430 normal controls recruited from Hunan province, southern China were typed for human leukocyte antigen (HLA)-B locus by Sanger sequencing exons 2–4. Besides confirming the NPC association with HLA-B*46:01 allele, HLA-A*02:07-B*46:01 and HLA-A*33:03-B*58:01 haplotypes (all positive), and HLA-B*13 lineage (negative), all of which were relatively common, strong negative associations were observed for five low-frequency and rare alleles or lineages, including HLA-B*07, -B*27:04, -B*39, -B*51:02 and -B*55:02, with odds ratio (OR) ranging from 0.16 to 0.3 (all pcorrected < 0.05). These strong protective associations were independent of linkage disequilibrium (LD) between HLA-A and HLA-B loci. Further analysis indicated a single amino acid change from histidine to tyrosine at residue 171 is probably crucial for the mutant allele, HLA-B*51:02, to mediate resistance to NPC. A subset of NPC cases (n = 821) and normal controls (n = 1,035) were tested for antivirus capsid antigen immunoglobulin A (anti-VCA IgA), which differed drastically between the two groups [67.7% vs. 5.5%, OR (95% confidence interval) = 36 (26.55–48.81), p < 0.0001]. HLA-B allelic variation did not associate with seropositivity for anti-VCA IgA in either group. Results from our study show, more clearly than previously, the existence of a cluster of low-frequency and rare HLA-B variants conferring low, or very low risk to NPC, a phenomenon not observed in other ethnic groups. Our data shed new insights into genetic susceptibility to NPC in southern Chinese populations. Future independent studies are warranted to replicate the findings reported in our study.
KW - HLA-B
KW - nasopharyngeal carcinoma
KW - rare allele
KW - sequencing
KW - southern Chinese population
UR - http://www.scopus.com/inward/record.url?scp=85083156604&partnerID=8YFLogxK
U2 - 10.1002/ijc.32992
DO - 10.1002/ijc.32992
M3 - Article
C2 - 32212153
AN - SCOPUS:85083156604
VL - 147
SP - 1397
EP - 1404
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 5
ER -