TY - JOUR
T1 - Gender-specific associations between MICA-STR and nasopharyngeal carcinoma in a southern Chinese Han population
AU - Tian, Wei
AU - Zeng, Xiao Min
AU - Li, Li Xin
AU - Jin, He Kun
AU - Luo, Qi Zhi
AU - Wang, Fan
AU - Guo, Shi Shi
AU - Cao, Ya
N1 - Funding Information:
Acknowledgements The authors wish to thank the two anonymous reviewers for their very helpful comments and suggestions. This work was supported by grants from the National Natural Science Foundation of China (Proj. No. 30300311), the Outstanding Youth Science Foundation of Hunan Province (Proj. No. 04JJ1007), and Central South University. We express our gratitude to Dr. Patricia A. Fraser for providing four reference DNA samples.
PY - 2006/4
Y1 - 2006/4
N2 - Previous studies have identified several HLA-B specificities that are associated with nasopharyngeal carcinoma (NPC) in populations of Chinese descent, in particular HLA-B35, -B38, -B46, and -B58. Perhaps except for HLA-B46, other associations cannot be simply accounted for by the linkage disequilibrium between HLA-A and B loci. The human major histocompatibility complex (MHC) class I chain-related gene A (MICA) maps 46 kb centromeric to HLA-B and is highly polymorphic; it encodes a stress-inducible protein which functions as a ligand for the NKG2D/DAP10 complex to activate natural killer (NK) cells, γδ T cells, and CD8+ T cells. We postulated MICA gene as a susceptibility factor for nasopharyngeal carcinoma, an Epstein-Barr virus-associated malignancy. In this study, 218 unrelated patients newly diagnosed with NPC and 196 randomly selected healthy controls from southern China mainland were analyzed for the short tandem repeat polymorphism of exon 5 of MICA gene (MICA-STR) and MICA gene deletion, using fluorescent polymerase chain reaction-gene scanning (PCR/size-sequencing) and polymerase chain reaction-sequence-specific priming (PCR/SSP) technology. MICA*A9 was present at significantly increased frequency in the patient group (P C=0.0001002, OR=2.528, 95% CI=1.636-3.907), whereas the frequency of MICA*A5.1 was significantly decreased (PC=0-006, OR=0.594, 95% CI=0.437-0.806). Gender-based stratification revealed a significant increase of MICA*A9 frequency (PC=0.000072, OR=3.255, 95% CI=1.855-5.709) and a significant decrease of MICA* A5.1 frequency (PC=0. 000737, OR=0.486, 95% CI=0.337-0.702) in male patients with NPC (N=166), compared with male normal controls (N=120). A significant interaction between MICA*A9 and gender was observed (XW2 =41.58, P=0.0001). Statistics also revealed heterogeneity of effects among MICA*A5.1/ MICA*A9-bearing phenotypes and a dose-dependent effect of MICA*A5.1 and MICA*A9 on NPC risk in male subgroup. This constitutes the first demonstration of a gender-specific association between MICA-STR polymorphism and NPC, which could largely be attributable to the underlying gender-related mechanisms that modulate MICA gene expression. The results provide strong supporting evidence suggesting that MICA*A9 may be a genetic risk factor for NPC in male individuals in this population. The potential interaction between MICA and other non-HLA host factors and environmental exposures remains to be further studied.
AB - Previous studies have identified several HLA-B specificities that are associated with nasopharyngeal carcinoma (NPC) in populations of Chinese descent, in particular HLA-B35, -B38, -B46, and -B58. Perhaps except for HLA-B46, other associations cannot be simply accounted for by the linkage disequilibrium between HLA-A and B loci. The human major histocompatibility complex (MHC) class I chain-related gene A (MICA) maps 46 kb centromeric to HLA-B and is highly polymorphic; it encodes a stress-inducible protein which functions as a ligand for the NKG2D/DAP10 complex to activate natural killer (NK) cells, γδ T cells, and CD8+ T cells. We postulated MICA gene as a susceptibility factor for nasopharyngeal carcinoma, an Epstein-Barr virus-associated malignancy. In this study, 218 unrelated patients newly diagnosed with NPC and 196 randomly selected healthy controls from southern China mainland were analyzed for the short tandem repeat polymorphism of exon 5 of MICA gene (MICA-STR) and MICA gene deletion, using fluorescent polymerase chain reaction-gene scanning (PCR/size-sequencing) and polymerase chain reaction-sequence-specific priming (PCR/SSP) technology. MICA*A9 was present at significantly increased frequency in the patient group (P C=0.0001002, OR=2.528, 95% CI=1.636-3.907), whereas the frequency of MICA*A5.1 was significantly decreased (PC=0-006, OR=0.594, 95% CI=0.437-0.806). Gender-based stratification revealed a significant increase of MICA*A9 frequency (PC=0.000072, OR=3.255, 95% CI=1.855-5.709) and a significant decrease of MICA* A5.1 frequency (PC=0. 000737, OR=0.486, 95% CI=0.337-0.702) in male patients with NPC (N=166), compared with male normal controls (N=120). A significant interaction between MICA*A9 and gender was observed (XW2 =41.58, P=0.0001). Statistics also revealed heterogeneity of effects among MICA*A5.1/ MICA*A9-bearing phenotypes and a dose-dependent effect of MICA*A5.1 and MICA*A9 on NPC risk in male subgroup. This constitutes the first demonstration of a gender-specific association between MICA-STR polymorphism and NPC, which could largely be attributable to the underlying gender-related mechanisms that modulate MICA gene expression. The results provide strong supporting evidence suggesting that MICA*A9 may be a genetic risk factor for NPC in male individuals in this population. The potential interaction between MICA and other non-HLA host factors and environmental exposures remains to be further studied.
KW - Gender
KW - Human leukocyte antigen
KW - MHC class-i chain-related gene A
KW - Microsatellite DNA
KW - Nasopharyngeal carcinoma
UR - http://www.scopus.com/inward/record.url?scp=33645471753&partnerID=8YFLogxK
U2 - 10.1007/s00251-006-0093-6
DO - 10.1007/s00251-006-0093-6
M3 - Article
C2 - 16547745
AN - SCOPUS:33645471753
VL - 58
SP - 113
EP - 121
JO - Immunogenetics
JF - Immunogenetics
SN - 0093-7711
IS - 2-3
ER -