We investigated whether GSTT1 ("null" allele), GSTM1 ("null"allele), GSTP1 (A313G), RFC1 (G80A), MTHFR (C677T), TS (2R/3R) polymorphisms were associated with toxicity and survival in patients with early breast cancer (EBC) treated with adjuvant chemotherapy (CT).
Genetic polymorphisms of glutathione S-transferase (GST) genes including GSTT1 positive/null, GSTM1 positive/null, and GSTP1 A313G, and genes for reduced folate carrier 1 G80A (RFC1 G80A), methylenetetrahydrofolate reductase C677T (MTHFR C677T), and breast cancer resistant protein C421A (BCRP C421A) were determined for 26 patients by the polymerase chain reaction (PCR) method or by direct sequencing.
Trends in the association between urinary ITC and breast cancer were more consistent with homozygous deletion of GSTM1 or GSTT1, the AAgenotype of GSTP1 (A313G), or with the C allele of NADPH quinine oxidoreductase (C609T), although interactions were not statistically significant.
Although the authors first determined whether genotypes of drug-metabolizing enzymes and transporters--glutathione S-transferase (GST) genes, GSTM1 positive/null, GSTT1 positive/null and GSTP1 A313G, methylenetetrahydrofolate reductase (MTHFR) C677T, reduced folate carrier 1 (RFC1) G80A, and breast cancer resistant protein (BCRP) C421A--were associated with hepatotoxicity for 24 patients, no significant difference was detected for genotype and allelic frequencies between the patients with and those without severe treatment-related hepatotoxicity.