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Multiple Genetic Polymorphisms of GSTP1 313AG, MDR1 3435CC, and MTHFR 677CC Highly Correlated with Early Relapse of Breast Cancer Patients in Taiwan

¹ Graduate Institute of Medicine, Kaohsiung Medical University, 100 Shin-Chuan 1st Rd, Kaohsiung 807, Taiwan
² Department of Radiation Oncology, Kaohsiung Medical University Hospital, 100 Zihyou1st Rd, Kaohsiung 807, Taiwan
³ Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shin-Chuan 1st Rd, Kaohsiung 807, Taiwan
⁴ Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 100 Zihyou 1st Rd, Kaohsiung 807, Taiwan
⁵ Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shin-Chuan 1st Rd, Kaohsiung 807, Taiwan
⁶ Laboratory Medicine, Kaohsiung Medical University Hospital, 100 Zihyou 1st Rd, Kaohsiung 807, Taiwan
⁷ Graduate Institute of Medical Genetics, Kaohsiung Medical University, 100 Shin-Chuan 1st Rd, Kaohsiung 807, Taiwan
⁸ Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, 100 Shin-Chuan 1st Rd, Kaohsiung 807, Taiwan

Correspondence: Address correspondence and reprint requests to: Shiu-Ru Lin, PhD; E-mail: srlin{at}ms2.hinet.net; and Jaw-Yuan Wang, MD, PhD; E-mail: cy614112{at}ms14.hinet.net

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.

Key Words: Breast cancer • Early relapse • Multiple genetic polymor-phisms • GSTP1 • MDR1 • MTHFR