title: A case-control and a family-based association study revealing an association between CYP2E1 polymorphisms and nasopharyngeal carcinoma risk in Cantonese.
abstract: 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 probably 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 single-nucleotide polymorphism approach. A total of 2499 individuals from 546 nuclear families were initially genotyped for the family-based association study. Single-nucleotide polymorphisms (SNPs) rs9418990, rs915908, rs8192780, rs1536826, rs3827688 and one haplotype h2 (CGTGTTAA) were revealed to be significantly associated with the NPC phenotype (P = 0.045-0.003 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 <46 years of age and had a history of cigarette smoking, with odds ratios (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 <0.015 for six SNPs, suggesting that the reported associations are less probably to be false. This study provides robust evidence for associations between genetic variants of CYP2E1 and NPC risk.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China. jiaweih@mail.sysu.edu.cn
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Pan
authors.forename: Hai-De
authors.initials: HD
authors.lastname: Qin
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Xu
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shen
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Chen
authors.forename: Qi-Sheng
authors.initials: QS
authors.lastname: Feng
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Hong
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Yin Yao
authors.initials: YY
authors.lastname: Shugart
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000235:genetics; D002277:Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005189:False Positive Reactions; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D000956:Antigens, Viral; D019392:Cytochrome P-450 CYP2E1