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Association of CYP1A1 and CYP2D6 gene polymorphisms with head and neck cancer in Tunisian patients

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Abstract

The purpose of this study was to investigate the relationship between head and neck cancer (HNC) and environmental agents and polymorphisms in CYP1A1, CYP2D6, NAT1 and NAT2 metabolic enzymes genes. To the best of our knowledge, this is the first report on polymorphisms in CYP1A1 6310C>T, CYP2D6 Arg365His, NAT1 52936A>T and NAT2 Arg268Lys (NAT2*12A) genes and susceptibility to HNC in Tunisian population. We study the prevalence of these polymorphisms in 169 patients with HNC and 261 control subjects using polymerase chain reaction based methods in a Tunisian population. We detected an association between HNC and CYP1A1 6310C>T (TT) and CYP2D6 Arg365His (His/His) variant carriers (OR 1.75, P = 0.008 and OR 1.66, P = 0.016, respectively). No association was found between the polymorphisms genotypes of NAT1 52936T>A and NAT2 Arg268Lys and risk of HNC. An association between HNC and CYP1A1 (TT) genotype was found among patients with smoking (P = 0.011) and drinking habit (P = 0.009). The combinations of NAT1 (AT or AA) and NAT2 (AA) at-risk genotypes increased HNC risk (OR 4.23, P = 0.005 and OR 3.60, P = 0.048, respectively). However, the combinations of CYP1A1 (AA) and CYP2D6 (CC) genotypes decreased risk of HNC (OR 0.20; P = 0.006). Genetic polymorphisms in CYP1A1 and CYP2D6 may significantly associate with HNC in the Tunisian population. The results of this study suggest a possible gene–environment interaction for certain carcinogen metabolizing enzymes, but larger studies that fully evaluate the interaction are needed.

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Abbreviations

CYP450:

Cytochrome P450

CI:

Confidence interval

CY:

Consumption-year

HNC:

Head and neck cancer

LC:

Laryngeal cancer

NPC:

Nasopharyngeal cancer

NAT:

N-Acetyl-transferase

OR:

Odds ratio

PY:

Pack-years

PCR:

Polymerase chain reaction

RFLP:

Restriction fragment length polymorphism

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Acknowledgments

This work was supported by the Ministry of Higher Education and Scientific Research, Tunisia. We thank the Department of Otorhinolaryngology, Habib Borguiba Hospital, Sfax, Tunisia for the recruitment of patients. We thank all members of this Department of and specially Dr Adel Chakroun and Dr Bouthaina Hammami for their efforts and assistance in recruiting patients.

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The authors declare that they have no conflict of interest.

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Khlifi, R., Chakroun, A., Hamza-Chaffai, A. et al. Association of CYP1A1 and CYP2D6 gene polymorphisms with head and neck cancer in Tunisian patients. Mol Biol Rep 41, 2591–2600 (2014). https://doi.org/10.1007/s11033-014-3117-6

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