A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma

• Published in: Journal of human genetics Vol. 54; no. 7; pp. 392 - 397
• Main Authors: Ng, Ching Ching, Yew, Poh Yin, Puah, Suat Moi, Krishnan, Gopala, Yap, Lee Fah, Teo, Soo Hwang, Lim, Paul Vey Hong, Govindaraju, Selvaratnam, Ratnavelu, Kananathan, Sam, Choon Kook, Takahashi, Atsushi, Kubo, Michiaki, Kamatani, Naoyuki, Nakamura, Yusuke, Mushiroda, Taisei
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-07-2009
• Subjects: Adolescent; Adult; Aged; Alleles; Asian Continental Ancestry Group - genetics; Case-Control Studies; Chromosome 3; Female; Genetic diversity; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotyping; Humans; Integrins - genetics; Linkage disequilibrium; Linkage Disequilibrium - genetics; Malaysia; Male; Middle Aged; Nasopharyngeal carcinoma; Nasopharyngeal Neoplasms - genetics; Polymorphism, Single Nucleotide - genetics; Reproducibility of Results; Single-nucleotide polymorphism; Throat cancer; Young Adult; Malaysia
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/jhg.2009.49

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-alpha 9) gene, rs2212020, to be strongly associated with NPC (P=8.27 x 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 x 10(-8) (OR=3.18, 95% CI=1.94-5.21), suggesting that a genetic variation(s) in ITGA9 may influence susceptibility to NPC in the Malaysian Chinese population.