Abbas Mohammad, Srivastava Kirti, Imran Mohd, Banerjee Monisha
Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India.
Department of Radiotherapy, King George's Medical University, Lucknow 226003, Uttar Pradesh, India.
Eur J Obstet Gynecol Reprod Biol. 2014 May;176:68-74. doi: 10.1016/j.ejogrb.2014.02.036. Epub 2014 Mar 4.
To evaluate the association of CYP1A1 gene polymorphisms with cervical cancer susceptibility in general and in relation to tobacco smoking.
The study included 408 subjects from North India (208 controls and 200 cases). All subjects were genotyped for CYP1A1 m1 T>C (rs4646903) and m2 A>G (rs1048943) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by statistical analysis (SPSS, version 15.0; SHEsis online version).
In our population, individuals with TC and CC genotypes of CYP1A1 m1 polymorphism have significantly higher risk of cervical cancer (adjusted odds (OR) 2.76, P=0.001; 3.13, P=0.006 respectively). In the case of m2 polymorphism, individuals with AG and GG genotypes show increased risk of cervical cancer (OR 1.90, P=0.021; and 3.05, P=0.285 respectively). The 'C' allele of m1 and 'G' allele of m2 polymorphism were strongly associated with the disease (P<0.0001 and 0.008 respectively). Multiple combinations showed that women carrying the genotypes viz. TC/AA (+/-), TC/AG (+/+), CC/AG (-/+) and CC/AG (+/+) were at higher risk of developing cervical cancer. The relationship between CYP1A1 m1 and m2 genotypes and tobacco smoking showed an 8-11-fold higher risk of cervical cancer amongst active smokers and 3-4-fold in passive smokers as well. Linkage disequilibrium between m1 and m2 showed highly significant association in the case of TA* (P<0.0001) haplotype, while 'CG' appeared to be the risk haplotype (P=0.002).
Our results suggest that presence of the 'C' allele of m1 (T>C) and 'G' of m2 (A>G) may be the risk alleles for cervical cancer susceptibility. Moreover, CYP1A1 m1 and m2 polymorphisms show considerable association with tobacco smoking in our study population.
评估CYP1A1基因多态性与宫颈癌易感性之间的总体关联以及与吸烟的关系。
该研究纳入了来自印度北部的408名受试者（208名对照和200例病例）。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对所有受试者进行CYP1A1 m1 T>C（rs4646903）和m2 A>G（rs1048943）基因分型，随后进行统计分析（SPSS 15.0版；SHEsis在线版）。
在我们的人群中，CYP1A1 m1多态性的TC和CC基因型个体患宫颈癌的风险显著更高（调整后的优势比（OR）分别为2.76，P=0.001；3.13，P=0.006）。在m2多态性方面，AG和GG基因型个体患宫颈癌的风险增加（OR分别为1.90，P=0.021；3.05，P=0.0285）。m1的“C”等位基因和m2多态性的“G”等位基因与该疾病密切相关（P分别<0.0001和0.008）。多种组合显示，携带TC/AA（+/-）、TC/AG（+/+）、CC/AG（-/ +）和CC/AG（+/ +）基因型的女性患宫颈癌的风险更高。CYP1A1 m1和m2基因型与吸烟之间的关系表明，主动吸烟者患宫颈癌的风险高8至11倍，被动吸烟者高3至4倍。m1和m2之间的连锁不平衡在TA*单倍型的情况下显示出高度显著的关联（P<0.0001），而“CG”似乎是风险单倍型（P=0.002）。
我们的结果表明，m1（T>C）的“C”等位基因和m2（A>G）的“G”等位基因的存在可能是宫颈癌易感性的风险等位基因。此外，在我们的研究人群中，CYP1A1 m1和m2多态性与吸烟有显著关联。
