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Advances in Respiratory Cancerogenesis

Volume 911 of the series Advances in Experimental Medicine and Biology pp 23-32

Date:

Associations of CYP1A2 Polymorphisms with the Risk Haplotypes in Lung Cancer in the Slovak Population

  • T. MatakovaAffiliated withDepartment of Medical Biochemistry, Comenius University in Bratislava
  • , E. HalasovaAffiliated withDepartment of Medical Biology, Comenius University in Bratislava
  • , A. DzianAffiliated withClinic of Thoracic Surgery and University Hospital Martin, Comenius University in Bratislava Email author 
  • , R. HrubyAffiliated withDepartment of Oncology, Hospital in Zilina
  • , M. HalasaAffiliated withClinic Surgery and Transplant Center, University Hospital in Martin
  • , K. JavorkaAffiliated withDepartment of Midwifery, Catholic University in Ruzomberok
  • , M. SkerenovaAffiliated withDepartment of Clinical Biochemistry, University Hospital in Martin

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Abstract

Phase I enzymes, including cytochrome P450, family 1, subfamily A, and polypeptide 2 (CYP1A2), are involved in the activation of carcinogens to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of present study was to investigate the association of CYP1A2 gene polymorphisms and haplotypes with lung cancer risk. A case-control study was carried out on 105 lung cancer patients and 189 controls. To investigate three CYP1A2 polymorphisms: rs2472299, rs2470890, rs11072508 we used a high resolution melting analysis. We found significant allele associations (rs2470890 and rs2422299) with lung cancer risk. We searched for meaningful associations for all variants in the dominant, recessive, and additive genetic models. Genotype associations in the recessive model were of marginal significance for the same single nucleotide polymorphisms. A haplotype analysis included five variants with the frequency higher than 1 %. The haplotype “acc”, present with the highest frequency, was associated with increased lung cancer risk (38.7 % vs. 31.5 %; OR 1.38; 95 %CI 0.95–2.01). On the contrary, rare haplotype “gtc” was significantly associated with decreased lung cancer risk in the Slovak population. In conclusion, the present study identified the risk alleles and haploid genotype associations of the CYP1A2 gene in lung cancer.

Keywords

Carcinogenesis Cytochrome P450 Genotyping Haplotypes CYP1A2 Lung cancer Polymorphisms CYP1A2