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Background  Polymorphisms in the Glutathione S-transferase genes are associated with altered risks in many cancers, but their role in oesophageal cancer is unclear. Recently a 37-kb deletion polymorphism of  GSTT2B  that reduces expression of  GSTT2  has been described. We evaluated the influence of the  GSTT1  and  GSTT2B  deletion polymorphisms, and the  GSTP1  Ile105Val polymorphism (rs1695) on susceptibility to oesophageal squamous cell carcinoma (OSCC) in the Black and Mixed Ancestry populations of South Africa.    Methods and Results  The  GSTT1 ,  GSTT2B  and  GSTP1  variants were genotyped in 562 OSCC cases and 907 controls, and tested for association with OSCC and for interaction with smoking and alcohol consumption. Linkage disequilibrium (LD) between the deletions at  GSTT1  and  GSTT2B  was determined, and the haplotypes tested for association with OSCC. Neither the  GSTT1  deletion nor the  GSTP1  Ile105Val polymorphism was associated with OSCC risk in the Black or Mixed Ancestry populations. The  GSTT2B  deletion was not associated with OSCC risk in the Black population, but was associated with reduced risk of OSCC in the Mixed Ancestry population (OR = 0.71; 95% CI 0.57–0.90, p = 0.004). Case-only analysis showed no interaction between the  GS T polymorphisms and smoking or alcohol consumption. LD between the neighboring  GSTT1  and  GSTT2B  deletions was low in both populations (r 2   Black  = 0.04; r 2   MxA  = 0.07), thus these deletions should be assessed independently for effects on disease risk.    Conclusions  Although there was no association between the  GSTT1  deletion polymorphism or the  GSTP1  Ile105Val polymorphism with OSCC, our results suggest that the presence of the recently described  GSTT2B  deletion may have a protective effect on the risk of OSCC in the Mixed Ancestry South African population. This is the first report of the contribution of the  GSTT2B  deletion to cancer risk.

Association of a Deletion of GSTT2B with an Altered Risk of Oesophageal Squamous Cell Carcinoma in a South African Population: A Case-Control Study