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Archives of Industrial Hygiene and Toxicology, Vol. 67 No. 4, 2016.

Original scientific paper

https://doi.org/10.1515/aiht-2016-67-2812

Association between the TP53 and CYP2E1*5B gene polymorphisms and non-small cell lung cancer

Ahmet Oguz Ada ; Department of Toxicology, Faculty of Pharmacy, University of Ankara, Ankara, Turkey
Serdar Bilgen ; Department of Toxicology, Faculty of Pharmacy, University of Ankara, Ankara, Turkey
Volkan Karacaoglan ; Department of Toxicology, Faculty of Pharmacy, University of Ankara, Ankara, Turkey
Celalettin Semih Kunak ; Department of Toxicology, Faculty of Pharmacy, University of Ankara, Ankara, Turkey
Emre Soydas ; Department of Toxicology, Faculty of Pharmacy, University of Ankara, Ankara, Turkey
Sibel Alpar ; Ataturk Pulmonary Diseases and Thoracic Surgery Hospital, Ankara, Turkey
Meral Gulhan ; Ataturk Pulmonary Diseases and Thoracic Surgery Hospital, Ankara, Turkey
Mumtaz Iscan ; Department of Toxicology, Faculty of Pharmacy, University of Ankara, Ankara, Turkey

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Abstract

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Genetic polymorphisms in tumour suppressor genes and genes encoding xenobiotic metabolising enzymes alter the activity of their corresponding enzymes and are important individual susceptibility factors for NSCLC. Because of the lack of information in literature, the aim of our study was to investigate the role of the tumour suppressor gene TP53 (Arg72Pro) and the xenobiotic metabolizing CYP2E1*5B gene polymorphisms on the risk of NSCLC development. The study population consisted of 172 patients and 172 controls (156 men and 16 women in each group). Genetic polymorphisms were determined with real-time polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). Multivariate analysis showed a significant association with NSCLC for the combination between the TP53 codon72 Arg/Pro and the Pro/Pro genotypes (OR 2.21, 95 % CI 1.39–3.51; p=0.001). We also analysed whether combinations of these gene variants with GSTM1, GSTT1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) gene polymorphisms were associated with the NSCLC risk. A significant increase in the risk was observed for the following combinations: TP53 codon72 variant with GSTM1 null (OR 2.22, 95 % CI 1.23-4.04; p=0.009), GSTT1 null (OR 2.98, 95 % CI 1.49-5.94; p=0.002), and GSTP1 (Ala114Val) variant genotypes (OR 3.38, 95 % CI 1.54-7.41; p=0.002). Further studies with larger samples are needed to verify these findings.

Keywords

carcinogen metabolism; CYP2E1; genetic polymorphism; GST; NSCLC

Hrčak ID:

170513

URI

https://hrcak.srce.hr/170513

Publication date:

14.12.2016.

Article data in other languages: croatian

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