Susceptibility to multiple cutaneous basal cell carcinomas: significant interactions between glutathione S-transferase GSTM1 genotypes, skin type and male gender

A Heagerty,A Smith,Rc Strange,W Perkins,J Lear,P Jones,B Bowers,J Gilford,J English,J Alldersea,A Fryer

doi:10.1038/bjc.1996.8

Abstract

The factors that determine development of single and multiple primary cutaneous basal cell carcinomas (BCCs) are unclear. We describe a case-control study firstly, to examine the influence of allelism at the glutathione S-transferase GSTM1 and GSTT1 and cytochrome P450 CYP2D6 loci on susceptibility to these tumours and, secondly, to identify interactions between genotypes and relevant individual characteristics, such as skin type and gender. Frequency distributions for GSTM1 genotypes in cases and controls were not different, although the frequency of GSTM1 A/B was significantly lower (P = 0.048) in the multiple BCCs than in controls. We found no significant differences in the frequencies of GSTT1 and CYP2D6 genotypes in cases and controls. Interactions between genotypes were studied by comparing multinomial frequency distributions in mutually exclusive groups. These identified no differences between cases and controls for combinations of the putatively high risk GSTM1 null, GSTT1 null, CYP2D6 EM genotypes. Interactions between GSTM1 A/B and the CYP2D6 PM and GSTT1-positive genotypes were also not different. Frequency distributions of GSTM1 A/B with CYP2D6 EM in controls and multiple BCCs were significantly different (P = 0.033). The proportion of males in the multiple BCC group (61.3%) was greater than in controls (47.0%) and single BCC (52.2%), and the frequency of the combination GSTM1 null/male gender was significantly greater in patients with multiple tumours (P = 0.002). Frequency distributions of GSTM1 null/skin type 1 were also significantly different (P = 0.029) and the proportion of subjects who were GSTM1 null with skin type 1 was greater (P = 0.009) in the multiple BCC group. We examined the data for interactions between GSTM1 null/skin type 1/male gender by comparing frequency distributions of these factors in the single and multiple BCC groups. The distributions were almost significantly different (exact P = 0.051). No significant interactions between GSTT1 null or CYP2D6 EM and skin type 1 were identified. Comparisons of frequency distributions of smoking with the GSTM1 null, GSTT1 null and CYP2D6 EM genotypes identified no differences between patients with single and multiple tumours.

Highlights

We found no differences in the frequencies of GSTT1 genotypes in controls and the basal cell carcinomas (BCCs) case groups (Table I)
Interactions between GSTM1 null and male gender were examined by comparing multinomial frequency distributions (Table III); distributions in single and multiple BCC were significantly different and, the frequency of the combination GSTM 1 null/male gender was significantly greater in patients with multiple tumours
We examined the data for interactions between GSTM1 null/skin type 1/male gender by comparing multinomial frequency distributions of these factors in the single and multiple BCC groups

Summary

Genotype frequencies in cases and controls

The differences between frequency distributions of the three genotypes combined (CYP2D6 PM/GSTT1 expressers/GSTMl A/B) in the multiple BCC and single BCC cases and, multiple BCC and controls approached significance (x26= 11.24, exact P = 0.055 and X25 = 10.06, exact P = 0.067 respectively). These differences largely resulted from differences in the proportion of subjects with the combination GSTT1 positive/GSTM 1 A/B; the frequency of this combination was significantly lower 46 Tablet CYP2D6, GSTM1 and GSTT1 genotype frequencies in patients with single and multiple basal cell carcinomas of skin

GSTTI genotypes

Table III Interactions between male gender and GSTM I null

Skin type

Discussion