Carcinogenesis Advance Access published online on October 5, 2009
Carcinogenesis, doi:10.1093/carcin/bgp239
A Case-Control and a Family-Based Association Study Revealing an Association between CYP2E1 Polymorphisms and Nasopharyngeal Carcinoma Risk in Cantonese
1 State Key Laboratory of Oncology in Southern China
2 Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
3 Department of Statistics and Epidemiology, Sun Yat-sen University School of Public Health, Guangzhou, 510060, China
4 Department of Social Medicine, University of Bristol, White Ladies Road, UK
5 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
* Address for correspondence: Wei-Hua Jia, M.D, Ph.D, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou 510060, The People's Republic of China. E-mail: jiaweih{at}mail.sysu.edu.cn, Tel: 86 20 87343195, Fax: 86 20 87343392
Nasopharyngeal carcinoma (NPC) is rare in most parts of the world but is more prevalent in Southern China, especially in Guangdong. The cytochrome P450 2E1 (CYP2E1) has been recognized as one of the critically important enzymes involved in oxidizing carcinogens, and is likely to be associated with NPC carcinogenesis. To systematically investigate the association between genetic variants in CYP2E1 and NPC risk in Cantonese, two independent studies, a family-based association study and a case-control study, were conducted using the haplotype-tagging SNP approach. A total of 2,499 individuals from 546 nuclear families were initially genotyped for the family-based association study. SNPs rs9418990, rs915906, rs915908, rs8192780, rs1536826, rs3827688 and one haplotype h2 (CGTGTTAA) were revealed to be significantly associated with the NPC phenotype (P = 0.045 to 0.003 and P = 0.003, respectively). To follow up the initial study, a case-control study including 755 cases and 755 controls was conducted. Similar results were observed in the case-control study in individuals younger than 46 years of age and had a history of cigarette smoking, with ORs of specific genotypes ranging from 1.88 to 2.99 corresponding to SNP rs9418990, rs3813865, rs915906, rs2249695, rs8192780, rs1536826, rs3827688, and of haplotypes h2 with OR = 1.65 (P = 0.026), h5 (CCCGTTAA) with OR = 2.58 (P = 0.007). The values of false-positive report probability were less than 0.015 for six SNPs, suggesting that the reported associations are less likely to be false. This study provides robust evidence for associations between genetic variants of CYP2E1 and NPC risk.
# Equal contributors
Received July 17, 2009; revised September 7, 2009; accepted September 28, 2009.