To identify a gene(s) susceptible to nasopharyngeal carcinoma (NPC), we carried out a genome-wide association study (GWAS) through genotyping of more than 500 000 tag single-nucleotide polymorphisms (SNPs), using an initial sample set of 111 unrelated NPC patients and 260 controls of a Malaysian Chinese population. We further evaluated the top 200 SNPs showing the smallest P-values, using a replication sample set that consisted of 168 cases and 252 controls. The combined analysis of the two sets of samples found an SNP in intron 3 of the ITGA9 (integrin-α 9) gene, rs2212020, to be strongly associated with NPC (P8.27 × 10 7, odds ratio (OR)2.24, 95% confidence intervals (CI)1.59-3.15). The gene is located at 3p21 which is commonly deleted in NPC cells. We subsequently genotyped additional 19 tag SNPs within a 40-kb linkage disequilibrium (LD) block surrounding this landmark SNP. Among them, SNP rs189897 showed the strongest association with a P-value of 6.85 × 10 8 (OR3.18, 95% CI1.94-5.21), suggesting that a genetic variation(s) in ITGA9 may influence susceptibility to NPC in the Malaysian Chinese population.
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