Theta class glutathione s-transferase gstt1 genotypes and susceptibility to cervical neoplasia: Interactions with gstm1, cyp2d6 and smoking

Warwick, Adrian; Sarhanis, Panos; Redman, Charles; Pemble, Sally; Taylor, John B.; Ketterer, Brian; Jones, Peter; Alldersea, Julie; Gilford, Janice; Yengi, Lilian; Fryer, Anthony; Strange, Richard C.

Abstract

The factors that determine progression of cervical intraepithelial neoplasia (CIN) to squamous cell carcinoma (SCC) are unknown. Cigarette smoking is a risk factor, suggesting polymorphism at loci that encode carcinogenmetabolizing enzymes such as glutathione S-transferase (GSTT1, GSTM1) and cytochrome P450 (CYP2D6) may determine susceptibility to these cancers. We have studied the frequency of the null genotype at the theta class GSTT1 locus in women with low-grade CDS, high-grade CIN and SCC. The control group comprised women with normal cervical pathology suffering menorrhagia. We found the frequency of GSTT1 null in the control and case groups was not significantly different, though frequency distributions of combinations of the genotype with smoking in mutually exclusive groups in the high-grade CIN group and the other case groups were significantly different Interactive effects of GSTT1 null with the GSTM1 null and CYP2D6 EM genotypes, and cigarette smoking were also studied by comparing the multinomial frequency distributions of these factors over mutually exclusive categories. These showed no significant differences between the controls and SCC or low-grade CIN. Frequency distributions in high-grade CIN, however, were significantly different to the controls, and both SCC and low-grade CIN; frequency distributions of GSTT1 null with smoking and CYP2D6 EM, individually and in combination, were significantly different However, inspection of our data does not indicate that GSTT1 null is a major factor mediating risk. Thus, comparison of χ2 values for the differences between frequency distributions in high-grade CIN and other groups shows that values for combinations of GSTT1 null with other factors are lower than those for equivalent combinations with smoking and CYP2D6 EM. Interestingly, the combination GSTT1 null/GSTM1 null did not appear to influence susceptibility to CIN or SCC.

Citation

Warwick, A., Sarhanis, P., Redman, C., Pemble, S., Taylor, J. B., Ketterer, B., …Strange, R. C. (1994). Theta class glutathione s-transferase gstt1 genotypes and susceptibility to cervical neoplasia: Interactions with gstm1, cyp2d6 and smoking. Carcinogenesis, 15(12), 2841–2845. https://doi.org/10.1093/carcin/15.12.2841

• Journal Article Type: Article
• Acceptance Date: Aug 31, 1994
• Publication Date: 1994-12
• Deposit Date: Feb 8, 2024
• Journal: Carcinogenesis
• Print ISSN: 0143-3334
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 12
• Pages: 2841–2845
• DOI: https://doi.org/10.1093/carcin/15.12.2841
• Publisher URL: https://academic.oup.com/carcin/article/15/12/2841/295537