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Gender-specific associations between MICA-STR and nasopharyngeal carcinoma in a southern Chinese Han population

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Abstract

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 (P C=0.006, OR=0.594, 95% CI=0.437–0.806). Gender-based stratification revealed a significant increase of MICA*A9 frequency (P C=0.000072, OR=3.255, 95% CI=1.855–5.709) and a significant decrease of MICA*A5.1 frequency (P C=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 (\({\text{X}}_{{W^{2} }} \)=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.

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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.

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Authors and Affiliations

  1. Department of Immunology, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan, 410078, People’s Republic of China

    Wei Tian, Li-xin Li, Qi-zhi Luo, Fan Wang & Shi-shi Guo

  2. Cancer Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan, 410078, People’s Republic of China

    Wei Tian & Ya Cao

  3. Department of Epidemiology and Statistics, Xiang-Ya School of Public Health, Central South University, Changsha, Hunan, 410078, People’s Republic of China

    Xiao-min Zeng

  4. Department of Radiotherapy, Oncology Hospital of Hunan Province, Changsha, Hunan, 410006, People’s Republic of China

    He-kun Jin

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  1. Wei Tian
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Correspondence to Ya Cao.

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Tian, W., Zeng, Xm., Li, Lx. et al. Gender-specific associations between MICA-STR and nasopharyngeal carcinoma in a southern Chinese Han population. Immunogenetics 58, 113–121 (2006). https://doi.org/10.1007/s00251-006-0093-6

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