243P - The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anticancer agents
Gastric Cancer
Translational Research
Presenter Tingting Zhao
Citation Annals of Oncology (2016) 27 (suppl_9): ix68-ix85. 10.1093/annonc/mdw582
Authors T. Zhao
  • Department Of Oncology Nanjing First Hospital Nanjing Medical University, Nanjing First Hospital, 210006 - Nanjing/CN

Abstract

Background

Objective 5-fluorouracil (5-FU) is widely used to treat patients with gastric cancer (GC). However, the response rate is quite heterogeneous. The single nucleotide polymorphisms (SNPs) and their interactions of genes in the one-carbon metabolism (OCM) pathway, including Methylenetetrahydrofolate reductase (MTHFR), Methionine synthase reductase (MTRR), Methionine synthase (MTR), and Thymidylate synthase (TS), significantly affect 5-FU metabolism.

Methods

In this study, 650 stage II-III patients were recruited from 1998 to 2006. Among them, 251 received 5-FU-based chemotherapy and other 399 patients were untreated. The Cox regression analysis, log-rank tests and Kaplan–Meier plots were adopted in our study.

Results

In the chemotherapy cohort, MTRR 66 GA + GG genotypes decreased the risk of death (HR = 0.657, 95% CI = 0.446-0.967, p = 0.031), however, the protect effect of MTRR 66 GA + GG disappeared when GC patients simultaneously had MTHFR 677TT + TC or MTR 2756GG + GA genotypes (HR = 0.871, 95% CI = 0.443-1.713; HR = 0.761, 95% CI = 0.451-1.287). TS 5′-UTR 2R3R + 3R3R genotypes also prolonged overall survival of patients treated with 5-FU (HR = 0.498, 95% CI = 0.259-0.960, p = 0.032). And this favorable prognosis obviously enhanced when GC patients simultaneously had TS 3′-UTR DD + DI and TS 5′-UTR 2R3R + 3R3R genotypes (HR = 0.332, 95% CI = 0.134-0.822, p = 0.046).

Conclusions

Our findings showed that the polymorphisms of MTRR 66 A > G and TS 5’-UTR 3R > 2R may be potential prognostic factors for GC patients receiving 5-FU-based regimens.

Clinical trial indentification

This is a linical trial, so I do not konw the trial protocol number and release date.

Legal entity responsible for the study

N/A

Funding

This work was partly supported by National 973 Basic Research Program of China (Grant No. 2013CB911300), Grants from National Natural Science Foundation of China (Grant No. 81572928) to Dr. Jinfei Chen;

Disclosure

All authors have declared no conflicts of interest.