Abstract
To investigate the glutathione S-transferase P1 (GSTP1) expression with chemotherapy polymorphisms involved in the prognosis of breast cancer patients with epirubicin or doxorubicin chemotherapy among breast cancer. 219 primary breast cancer patients who were consecutively recruited in our study have been treated with anthracycline-based (epirubicin [E] or doxorubicin [A]) chemotherapy between March 2006 and March 2007. All the patients were followed up until January 2012. Genotyping was based upon duplex polymerase-chain-reaction with polymerase chain reaction with confronting two-pair primers(PCR-CTPP) method. The frequencies of GSTP polymorphisms were found have significant difference in progesterone receptor status (P<0.05). GSTP1 Val/Val genotype had significantly higher rates of response to chemotherapy when compared to GSTP1 Ile/Ile genotype, and the adjusted odds ratios (OR) (95% confidence interval, CI) of 2.19 (1.23 to 4.21). Additionally, the GSTP1 Val allele genotype had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 1.71 (1.12 to 2.76). Patients with glutathione S-transferase M1 (GSTM1) null genotype had a longer average survival time and significantly lower risk of death than those with non-null genotypes [Hazard ratio (HR) (95% CI) = 0.66 (0.31 to 0.93)]. Similarly, those carrying GSTP1 Val/Val genotype had 0.54-fold the risk of death of those with GSTP1 Ile/Ile [HR (95% CI) = 0.54(0.29 to 0.90)]. GSTP1 expression was found to be associated with response to chemotherapy treatment of breast cancer and Estrogen receptor (ER) status had some mechanism between GSTP1 polymorphism and response to chemotherapy. Key words: Glutathione S-transferase P1 (GSTP1), breast cancer, epirubicin or doxorubicin chemotherapy.
Highlights
Breast cancer is by far the most frequent cancer among women with an estimated 1.38 million new cancer cases diagnosed in 2008 (23% of all cancers)
To investigate the glutathione S-transferase P1 (GSTP1) expression with chemotherapy polymorphisms involved in the prognosis of breast cancer patients with epirubicin or doxorubicin chemotherapy among breast cancer. 219 primary breast cancer patients who were consecutively recruited in our study have been treated with anthracycline-based chemotherapy between March 2006 and March 2007
There was no significant difference between patients with GSTP1 IIe/IIe genotype and those with IIe/Val or Val/Val genotype (Table 1)
Summary
Breast cancer is by far the most frequent cancer among women with an estimated 1.38 million new cancer cases diagnosed in 2008 (23% of all cancers). Anthracycline-based chemotherapy regimens are preferred for downstaging breast cancer tumors (Bafaloukos, 2005). GSTP1 is reported to be associated with resistance to chemotherapy in vitro studies (Satta et al, 1992; Whelan et al, 1992). GSTP1 was found to be associated with resistance to 5-fluorouracil (5-FU), doxorubicin, mitomycin C and paclitaxel (Su et al, 2003). The results of the relationship between GSTP1 and breast cancer with chemotherapy are conflicting (Peters et al, 1993; Schmidt et al, 2003). It is needed to explore the association between GSTP1 expression and response to chemotherapy. A prospective study to investigate the association of GSTs expression with response to neoadjuvant sequential epirubicin or doxorubicin chemotherapy among breast cancer patients was conducted
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