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Sequence Variants in Toll-Like Receptor 10 Are Associated with Nasopharyngeal Carcinoma Risk

¹ State Key Laboratory of Oncology in Southern China and ² Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China; and ³ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Requests for reprints: Yi-Xin Zeng, Sun Yat-sen University, Cancer Center, 651 Dong-Feng Road East, 510060 Guangzhou, China. Phone: 86-20-8734-3333; Fax: 86-20-8734-3295. E-mail: yxzeng{at}gzsums.edu.cn or Yin Yao Shugart, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Room E6516, 615 North Wolfe Street, Baltimore, MD 21205. E-mail: yyao{at}jhsph.edu

Nasopharyngeal carcinoma (NPC) is a common malignancy in southern China and Southeast Asia. Genetic susceptibility is a major factor in determining the individual risk of NPC in these areas. To test the association between NPC and variants in Toll-like receptor 10 (TLR10), we conducted a hospital-based case-control study in a Cantonese-speaking population in Guangdong province. Seven single nucleotide polymorphisms in TLR10, selected with a tagging algorithm, were genotyped. When assessing each unique haplotype compared with the most common haplotype, "GAGTGAA," with the expectation-maximization algorithm in Haplo.stats, the risk of developing NPC was significantly elevated among men who carried the haplotype "GCGTGGC" (P = 0.005). After adjusting for age, gender, and VCA-IgA antibody titers, this association was more significant (P = 0.0007). To further assess the overall differences of haplotype frequency profiles between cases and healthy controls, the global score test, considering all haplotypes and adjusting for age, gender, and VCA-IgA antibody titers, gave a haplo score of 27.52 with P = 0.002. The haplotype specific odds ratio was 2.66 (confidence interval, 1.34-3.82) for GCGTGGC. We concluded that in this Cantonese population–based study, haplotype GCGTGGC with frequency of 11.4% in TLR10 was found to be associated with NPC and this association was statistically significant after adjusting for age, gender, and VCA-IgA antibody titers. It is possible that this is not a causal haplotype for NPC; rather, it is in strong linkage disequilibrium with a causal single nucleotide polymorphism in close proximity. (Cancer Epidemiol Biomarkers Prev 2006;15(5):862–6)