SUSCEPTIBILITY TO MULTIPLE CUTANEOUS BASAL-CELL CARCINOMAS - SIGNIFICANT INTERACTIONS BETWEEN GLUTATHIONE-S-TRANSFERASE GSTM1 GENOTYPES, SKIN TYPE AND MALE GENDER

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 gl utathione S-transferase GSTM1 and GSTT1 and cytochrome P450 CYP2D6 loc i on susceptibility to these rumours and, secondly, to identify intera ctions 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 GS TM1 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 betwee n genotypes were studied by comparing multinomial Frequency distributi ons in mutually exclusive groups. These identified no differences betw een cases and controls for combinations of the putatively high risk GS TM1 null, GSTT1 null, CYP2D6 EM genotypes. Interactions between GSTM1 A/B and the CYP2D6 PM and GSTT1-positive genotypes were also not diffe rent. Frequency distributions of GSTM1 A/B with CYP2D6 EM in controls and multiple BCCs were significantly different (P = 0.033). The propor tion of males in the multiple BCC group (61.3%) was greater than in co ntrols (47.0%) and single BCC (52.2%), and the Frequency of the combin ation GSTM1 null/male gender was significantly greater in patients wit h multiple tumours (P = 0.002). Frequency distributions of GSTM1 null/ skin type 1 were also significantly different (P = 0.029) and the prop ortion 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 interact ions 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 = 0.05 1). No significant interactions between GSTT1 null or CYP2D6 EM and sk in type 1 were identified. Comparisons of frequency distributions of s moking with the GSTMI null, GSTT1 null and CYP2D6 Eh4 genotypes identi fied no differences between patients with single and multiple tumours.