GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis.

Cytosolic glutathione S-transferase comprises multiple isoenzymes; studies have principally examined mu-1 (GSTM1: null/present), theta-1 (GSTT1: null/present) and pi-1 (GSTP1 Ile105Val) gene polymorphisms concerning breast cancer risk. Regarding GSTT1 and GSTP1 polymorphisms, studies remain controversial and no recent meta-analysis has appeared. This meta-analysis aims to examine whether GSTT1 and GSTP1 polymorphisms are associated with breast cancer risk. Separate analyses were performed on Chinese and non-Chinese populations, in an attempt to investigate race-specific effects. Eligible articles were identified by a search of MEDLINE bibliographic database for the period up to August 2009. Regarding GSTT1 null/present genotype, 41 case-control studies were eligible (16,589 breast cancer cases and 19,995 controls); 30 case-control studies were eligible for GSTP1 Ile105Val (16,908 cases and 20,016 controls). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. At the overall analysis, the null GSTT1 genotype was associated with elevated breast cancer risk (pooled OR = 1.114, 95% CI: 1.035-1.199, random effects). However, the association seemed confined to non-Chinese populations (33 studies, pooled OR = 1.128, 95% CI: 1.042-1.221, random effects), given that the association was not significant in the subset of Chinese studies (eight studies, pooled OR = 1.061, 95% CI: 0.875-1.286, random effects). Regarding GSTP1 Ile105Val, no statistically significant associations were detected in non-Chinese populations (25 studies). On the other hand, the GG genotype was associated with increased breast cancer risk in Chinese populations (five studies, pooled OR = 1.297, 95% CI: 1.023-1.645, fixed effects); accordingly, the recessive model yielded statistically significant results (pooled OR = 1.273, 95% CI: 1.006-1.610, fixed effects). In conclusion, polymorphisms of both GSTT1 and GSTP1 genes seem associated with elevated breast cancer risk in a race-specific manner. Given the small number of Chinese studies, the finding on GSTP1 Ile105Val merits further investigation.

Duke Scholars

Author Konstantinos Economopoulos