Interaction between glutathione-S-transferase polymorphisms, smoking habit, and HPV infection in cervical cancer risk

Abstract

Purpose

Human papillomavirus (HPV) infection is considered the major cause of cervical cancer (CC), but a number of infected women do not develop invasive lesions, suggesting the role of genetic susceptibility and environmental co-factors for cancer outbreak. The aim of this study was to investigate whether some GST polymorphisms could influence the risk to develop CC, either by themselves or in combination with smoking habit, in a cohort of high-risk HPV (HR-HPV) infected Italian women.

Methods

The study population comprises 192 Italian women including 81 HR-HPV infected women bearing cervical lesions and 111 healthy controls. The cases include: 26 low-grade squamous intraepithelial lesions (LSILs), 30 high-grade-SIL, and 25 CCs, while controls were all negative for HPV. DNA was extracted from peripheral blood samples or cytobrush and individuals were genotyped for GSTM1, GSTT1, and GSTP1 polymorphisms using PCR and PCR/RFLP techniques.

Results

On studying the association of GSTs gene polymorphisms with cervical cancer lesions, the combination of GSTM1 null, GSTT1 null and GSTP1 AA genotypes, independently on smoking habit, seems to be related to a 5.7-fold increased risk of developing CLs with a considerable statistical significance (P = 0.0091).

Conclusions

We suggest that the investigation of multiple gene polymorphisms, versus single genes, could contribute to a better understanding of the effect of susceptibility genes on cancer risk.

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Acknowledgments

This study was supported by grants from the National Public Ministry of Health. We would like to thank Dr. Irene Terrenato and Dr. Maria Cecilia Cercato, from the Department of Epidemiology of the Regina Elena Cancer Insitute of Rome, for the statistical analysis and the epidemiological informations; Dr. P. Cordiali, Dr. L. Cilli, Dr. E. Trento, Dr. F. Stivali, Dr. A Giglio, Dr. D. Moretto, Dr. E Greco, Dr. A. Arancio from the SC Clinic Pathology Microbiology of the IRCCS San Gallicano Institute of Rome, for subject recruitment; Prof. P. Benedetti Panici from “La Sapienza” University of Rome and Dr. M. Giuliani from the IRCCS San Gallicano Institute of Rome.

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We declare that we have no conflict of interest.

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Correspondence to Antonella Testa.

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S. Palma and F. Novelli contributed equally to this work.

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Palma, S., Novelli, F., Padua, L. et al. Interaction between glutathione-S-transferase polymorphisms, smoking habit, and HPV infection in cervical cancer risk. J Cancer Res Clin Oncol 136, 1101–1109 (2010). https://doi.org/10.1007/s00432-009-0757-3

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Keywords

  • Cervical cancer
  • Human papillomavirus
  • Active smoke
  • Genetic polymorphisms
  • GSTs