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CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer

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Abstract

Purpose

As risk-modifiers of alcohol and tobacco effects, metabolic genes polymorphisms were investigated as susceptibility candidates for squamous cell carcinoma of the head and neck (SCCHN).

Methods

A total of 210 cases and 245 hospital controls, age and gender matched, were genotyped for CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms. A measurement of the biological interaction among two risk factors was estimated by the attributable proportion (AP) due to interaction and its 95% confidence interval (CI).

Results

SCCHN risk was associated with high-levels of alcohol intake [OR = 3.50 (95%CI: 1.93–6.35) and OR = 6.47 (95%CI: 2.92–14.35) for 19–30 g/day and >30 g/day, respectively], cigarette smoking [OR = 3.47 (95%CI: 1.88–6.41) and OR = 7.65 (95%CI: 4.20–13.90) for 1–25 and >25 pack-years of smoking, respectively] and low-fruit and vegetables consumption (OR = 2.45; 95%CI: 1.53–3.92). No differences were observed for the genotypes or haplotypes distributions among cases and controls, and no biological interaction emerged from gene–gene and gene–environment interaction analyses. An attributable proportion (AP) due to biological interaction of 0.65 (95%CI: 0.40–0.90) was detected for heavy drinkers with a low intake of fruit and vegetables, and an AP of 0.40 (95%CI: 0.10–0.72) resulted forever smokers with low fruit and vegetables consumption.

Conclusions

Even in presence of high alcohol consumption or cigarette smoking, a high intake of fruit and vegetables might prevent the development of around one quarter of SCCHN cases. The lack of interaction between the studied polymorphisms and the environmental exposures suggests that chronic consumption of tobacco and alcohol overwhelm enzyme defences, irrespective of genotype.

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Abbreviations

SCCHN:

Squamous cell carcinoma of the head and neck

CYP:

Cytochrome P-450

GST:

Glutathione S-transferase

NAT:

N-acetyltransferase 2

mEH:

microsomal Epoxide hydrolase

ORs:

Odds ratios

CI:

Confidence intervals

HWE:

Hardy–Weinberg equilibrium

AP:

Attributable proportion

DFS:

Disease free survival

HR:

Hazard ratio

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Acknowledgments

We are grateful to Francesco Gianfagna and Paola Galli for the assistance in the database management, to Rosarita Amore for the blood samples processing and to Wendy Morotti for the linguistic revision of the final manuscript.

Conflict of interest

All authors disclose any financial and personal relationships with other people or organisations that could inappropriately influence the work.

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Authors and Affiliations

  1. Genetic Epidemiology and Molecular Biology Unit, Institute of Hygiene, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy

    Stefania Boccia, Dario Arzani, Angelo De Lauretis & Gualtiero Ricciardi

  2. Otorhinolaryngology, Università Cattolica del Sacro Cuore, Rome, Italy

    Gabriella Cadoni, Mariangela Volante, Giovanni Almadori & Gaetano Paludetti

  3. Medicines Evaluation Board Agency, The Hague, The Netherlands

    Fakhredin A. Sayed-Tabatabaei

  4. Geriatric Medicine, Università Cattolica del Sacro Cuore, Rome, Italy

    Caterina Cattel

  5. Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands

    Cornelia M. van Duijn

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  1. Stefania Boccia
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  2. Gabriella Cadoni
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  3. Fakhredin A. Sayed-Tabatabaei
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Correspondence to Stefania Boccia.

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Boccia, S., Cadoni, G., Sayed-Tabatabaei, F.A. et al. CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer. J Cancer Res Clin Oncol 134, 93–100 (2008). https://doi.org/10.1007/s00432-007-0254-5

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  • DOI: https://doi.org/10.1007/s00432-007-0254-5

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