Association of cytochrome P450 1B1 haplotypes with head and neck cancer risk

作者：Katiyar Tridiv; Maurya Shailendra S; Hasan Feza; Singh Arvind P; Khan Anwar J; Hadi Rahat; Singh Sudhir; Bhatt Madan L B; Parmar Devendra^*

来源：Environmental and Molecular Mutagenesis, 2017, 58(6): 443-450.

DOI：10.1002/em.22098

• HNSCC
• tobacco
• CYP1B1
• haplotypes
• mRNA
• risk

Genetic polymorphisms have been reported in several cytochrome P450 (CYP) genes, including CYP1B1 which metabolically activates procarcinogens present in tobacco to carcinogenic intermediates. This study used a case-control approach in North Indian population to determine associations between genetic variants in CYP1B1 and risk of Head and Neck Squamous Cell Carcinoma (HNSCC). We examined the genotype and haplotype frequencies at various single-nucleotide polymorphisms (SNPs), including SNPs previously reported in the promoter region and intron 1 of CYP1B1 in Caucasians. Using cycle sequencing, 9 SNPs were identified in the promoter region, intron 1, and exons 2 and 3. Haplotype analysis revealed that 5 SNPs (those in the promoter region, intron, and Arg48Gly and Ala119Ser in exon 2) were in strong linkage disequilibrium (LD). Cases with the T-A-T-G-T haplotype were significantly associated with increased risk of HNSCC. Interestingly, qRT-PCR studies revealed a significant increase in mRNA expression of CYP1B1 in peripheral blood isolated from cases with the T-A-T-G-T haplotype compared with cases with the C-G-C-C-G haplotype, and in cases compared to controls for both main haplotypes. The data thus provide evidence that CYP1B1 haplotypes could be more effective in predicting HNSCC risk. Environ. Mol. Mutagen. 58:443-450, 2017.

• 出版日期2017-7
• 单位河北医科大学