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Authors Wang D, Zhang X, Zhang Y, Wu Y, Guan X, Zhu W, Wang M, Qi C, Shen B
Received 13 July 2018
Accepted for publication 29 September 2018
Published 13 November 2018 Volume 2018:11 Pages 8083—8088
DOI https://doi.org/10.2147/OTT.S180145
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Dr Yao Dai
Purpose: Several
studies have proved that single nucleotide polymorphisms (SNPs) of mismatch
repair system genes are closely related to the development of colorectal cancer
(CRC) by causing microsatellite instability, while effects of the SNPs of MMR
system-related genes on the clinical outcomes of cytotoxic chemotherapy are
less understood. The aim of this study explored the influence of MLH1 SNPs on
clinical outcomes of first-line irinotecan-based chemotherapy in CRC.
Patients and methods: A total of 125
metastatic colorectal cancer (mCRC) patients who received first-line
irinotecan-based chemotherapy (none of them combined with bevacizumab or
cetuximab) were enrolled in this study. Blood samples or formalin-fixed
paraffin-embedded tissues of study population were taken. DNA isolation and
genotyping analyzed were obtained for potential functional polymorphisms of
MLH1 rs1800734 by real-time PCR. Progression-free survival (PFS) was the
primary endpoint and tumor response rate (RR) was the secondary endpoint of
this study.
Results: Of all
the assessable population, the result showed no statistical difference among
the three types SNPs of MLH1 rs1800734 (AA, AG, GG) for RR (P =0.859), and also
without significant difference for AA + AG combined variants vs GG variant (P =0.849). The
median PFS for AA, AG, and GG variants of MLH1 rs1800734 SNPs were 9.4 months,
7.0 months, and 6.9 months, respectively (log-rank P =0.031).
Interestingly, compared with AA variant of MLH1 rs1800734 SNPs, GG variant
showed a shorter PFS (HR: 3.49; 95 CI: 1.02–11.94; P =0.046).
Furthermore, the median PFS of AA + AG combined variants and GG variant were
8.3 months and 6.9 months (log-rank P =0.037), and GG variant have a decreased trend with
no significant difference (HR: 1.57; 95 CI: 0.98–2.53; P =0.061).
Conclusion: The AA variant
of MLH1 rs1800734 SNPs has a longer PFS in first-line irinotecan-based
chemotherapy for mCRC patients, and the result needs to be further confirmed by
prospective studies in the future.
Keywords: MLH1 SNPs,
irinotecan, colorectal cancer