Role of GSTM1 and GSTT1 genotypes in differentiated thyroid cancer and interaction with lifestyle factors: Results from case-control studies in France and New Caledonia

PLoS One. 2020 Jan 30;15(1):e0228187. doi: 10.1371/journal.pone.0228187. eCollection 2020.

Abstract

Background: GSTM1 and GSTT1 are involved in detoxification of xenobiotics, products of oxidative stress and in steroid hormones metabolism. We investigated whether GSTM1 and GSTT1 gene deletion was associated with DTC risk and explored interaction with non-genetic risk factors of DTC.

Methods: The study included 661 DTC cases and 736 controls from two case-control studies conducted in France and New Caledonia. Odds ratios (OR) and their confidence interval (CI) for DTC associated with GST genotypes, alcohol drinking, tobacco smoking, body mass index and hormonal factors were calculated using logistic regression models.

Results: Results are presented for Europeans and Melanesians combined, as no heterogeneity between groups was detected. We found that DTC risk increased with obesity and decrease with alcohol drinking. After stratification by gene deletion status, the OR for obesity was 5.75, (95%CI 2.25-14.7) among individuals with GSTT1 and GSTM1-deleted genotype, and 1.26, (95%CI 0.89-1.77) in carriers of both genes (p-interaction = 0.02). The OR for drinking ≥1 glass/week was 0.33 (95%CI 0.15-0.74) in GSTT1-null individuals while it was 1.01 (95%CI 0.67-1.52) in non-null carriers of the gene (p-interaction = 0.01). No interaction between GST genotypes and other non-genetic risk factors was detected.

Conclusion: GSTM1 and GSTT1 genotypes may modulate the DTC risk associated with BMI and alcohol consumption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / adverse effects
  • Body Mass Index
  • Case-Control Studies
  • Female
  • Gene Deletion
  • Genotype
  • Glutathione Transferase / genetics*
  • Gonadal Steroid Hormones / metabolism
  • Health Risk Behaviors
  • Humans
  • Life Style*
  • Male
  • Middle Aged
  • New Caledonia
  • Obesity / complications
  • Thyroid Neoplasms / etiology
  • Thyroid Neoplasms / genetics*

Substances

  • Gonadal Steroid Hormones
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1

Grants and funding

The New Caledonia study was supported by grants from Fondation de France, Association pour la Recherche contre le Cancer (ARC), and Agence Française de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES, ex-AFSSET). The CATHY study was supported by grants from the ANSES, Ligue Nationale Contre le Cancer, Institut National du Cancer, Fondation de France, and the Epidemiology Committee of EDF. Catherine Tcheandjieu performed this work during her PhD studies with the support of Ecole des Hautes Etudes en Santé Publique (EHESP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.