Multiple Genetic Polymorphisms of GSTP1 313AG, MDR1 3435CC, and MTHFR 677CC highly correlated with early relapse of breast cancer patients in Taiwan.
BACKGROUND
Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets have been linked to inter-individual differences in the efficacy and toxicity of many medications. In the present study, multiple chemotherapeutic agent-related genetic polymorphisms, including GSTP1, MDR1, MTHFR, and TS tandem repeats, were analyzed in breast cancer patients and studied in correlation with the clinical outcome of patients receiving FEC adjuvant chemotherapy.


METHODS
The genotypes from 192 stage II and III breast cancer patients who underwent operations and received six cycles of postoperative adjuvant chemotherapy (FEC) were determined by means of PCR-RFLP. The association of each genetic polymorphism with clinicopathological data of patients and early relapse status were analyzed.


RESULTS
The results showed that the genotype distribution of GSTP1 A313G, MTHFR C677T, and TS 3R3R in Taiwanese subjects differed significantly from the distribution in Caucasians. After analysis of the relationship between the genotypes and clinicopathological data of the patients, a significant correlation was observed between postoperative early relapse in patients with genetic polymorphisms of both MDR1 3435CC and MTHFR 677CC (crude OR: 2.609, P = .013) and patients with additional GSTP1 313AG genetic polymorphism (crude OR: 2.833, P = .017).


CONCLUSIONS
The results of the present study highly suggest that GSTP1, MDR1, and MTHFR genotypes could be prognostic factors for Taiwanese patients with breast cancer.
Huang
Ming-Yii
MY
Graduate Institute of Medicine, Kaohsiung Medical University, 100 Shin-Chuan 1st Rd, Kaohsiung 807, Taiwan.
Wang
Yi-Hui
YH
Chen
Fang-Ming
FM
Lee
Su-Chen
SC
Fang
Wei-Yu
WY
Cheng
Tian-Lu
TL
Hou
Ming-Feng
MF
Wang
Jaw-Yuan
JY
Lin
Shiu-Ru
SR
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012008:Recurrence; D013624:Taiwan; D013940:Thymidylate Synthase / Q000235:genetics; D013997:Time Factors
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi