Research Article Cancer Reports and Reviews Cancer Rep Rev, 2018 doi: 10.15761/CRR.1000150 Volume 2(2): 1-7 ISSN: 2513-9290 GSTP1, TSER, MTHFR C677T and MTHFR A1298C gene single nucleotide polymorphisms associated with toxicity and survival in patients with colorectal cancer treated with 5-fuorouracil-based chemotherapy Necibe Dilan Polat 1 , Serkan Degirmencioglu 2 *, Arzu Yaren 2 , Aydın Demiray 3 , Hakan Akca 3 and Gamze Gököz Dogu 2 1 Pamukkale University Hospital Internal Medicine Department, Bagbasi, Denizli, Turkey 2 Pamukkale University Hospital Medical Oncology Department, Fahri Goksin Oncology Center, Bagbasi, Denizli, Turkey 3 Pamukkale University Hospital Medical Biology Department, Bagbasi, Denizli, Turkey Abstract Aim: Colorectal cancer is a potentially curable malignancy; but it remains as a fatal disease since it’s the second most common cause of cancer-related death globally. Currently, 5-Fluorouracil is the main chemotherapeutic agent used in combined therapies for the adjuvant and palliative treatment of colorectal cancer. Genetic polymorphisms have important roles in individual diferences which occur in response to cancer chemotherapy and toxicity. Te aim of this study is to evaluate association of 5-Fluorouracil metabolism-related MTHFR-677C>T, MTHFR-1298A>C, GSTP1-313A>G and TSER single nucleotide polymorphisms with chemotherapy response and toxicity. Methods: One hundred chemotherapy naive colorectal cancer patients were enrolled and their biochemical parameters evaluated. Mutation analysis of MTHFR- 677C>T, MTHFR 1298A>C, TSER and GSTP1-313A>G genes were studied in Molecular oncology laboratory of Medical Biology Department. Results: Tere was an association between GSTP1-313A>G A/G genotype and smoking. MTHFR-677C>T T/T ve C/T genotypes were related to neutropenia, high levels of CEA and CRP. MTHFR-1298A> C C/C genotype was associated with high levels of CRP and progression. High levels of CEA, CRP, diarrhea- constipation and neutrophilia were related to TSER-3R/3R and 2R/3R genotypes. In survival analysis, shorter disease free survival was observed for MTHFR- 1298A>C single nucleotide polymorphism C/C genotype in early stage patients. Conclusion: In this study, we have investigated single nucleotide polymorphisms of specifc enzymes involving in activity and metabolism of 5-FU and their association with response to chemotherapy and toxicity. Te limited number of patients has led us to the conclusion that our results should be supported by more comprehensive multi-centered studies. Correspondence to: Serkan Degirmencioglu, Pamukkale University Hospital, Fahri Goksin Oncology Center 20100 Denizli, Turkey, Tel: 902582965139/905358333655, E-mail: drserkandeg@hotmail.com Key words: colorectal cancer, GSTP, MTHFR, TSER, single nucleotide polymorphism, 5-Fluorouracil, toxicity, chemotherapy response Received: February 24, 2018; Accepted: March 05, 2018; Published: March 09, 2018 Introduction Colorectal cancer is a potentially curable malignancy; but it still remains as a fatal disease since it’s the second most common cause of cancer-related death globally with serious damage to human health [1]. Gene polymorphisms involve in both pathogenesis of colorectal cancer and metabolism of the drugs used in treatment (Fluorouracil (5-FU), oxaliplatin and irinotecan). While certain polymorphisms may lead to changes in efectiveness of the drugs, some others substantially increase toxicities of these drugs [2]. Tus, identifcation of polymorphisms may be efective in predicting clinical response to chemotherapy and chemotherapy-related toxicities in several types of cancer [3,4]. 5-Fluorouracil acts via fuorodeoxyuridine monophosphate (FdUMP). Tis molecule inhibits thymidylate synthase (TS) [5]. Reduction in methylenetetrahydrofolate reductase (MTHFR) enzyme activity may lead to an increase in intracellular 5,10-methylenetetrahydrofolate (5,10-MTHF) level and thus may increase FU cytotoxicity. MTHFR gene is localized to chromosome 1p36.3 [6]. Two types of single-nucleotide polymorphisms (SNPs) frequently develops on this enzyme: C677T (rs1801133) and A1298C (rs1801131) [7]. Alanine and valine exchanges their position as a result of C677T transition and thus form a more thermo-labile protein which reduces enzyme activity [8]. A1298C variant (Glu429Ala) also may reduce MTHFR enzymatic activity by leading to a missense mutation [9]. In C677T homozygous (TT) or heterozygous (CT) genotypic conditions MTHFR enzyme activity is downregulated and blood homocysteine level increases [10]. When A1298C enzyme changes to homozygous (CC) or heterozygous (AC) form from its normal (AA) form a reduction in MTHFR activity is observed but thermo-labile protein is not formed [11]. Reduced enzyme activity results with high levels of 5,10-MTHF and thymidine and thus leads to an increase in DNA synthesis and repair. Tus, MTHFR polymorphisms are