Cancer Res Treat.  2019 Jul;51(3):1198-1206. 10.4143/crt.2018.527.

Associations of Genetic Variations in Mismatch Repair Genes MSH3 and PMS1 with Acute Adverse Events and Survival in Patients with Rectal Cancer Receiving Postoperative Chemoradiotherapy

• Yang J
• Huang Y
• Feng Y
• Li H
• Feng T
• Chen J
• Yin L
• Wang W
• Wang S
• Liu Y
• Song Y
• Li Y
• Jin J
• Tan W
• Lin D

• KMID: 2454311
• DOI: http://doi.org/10.4143/crt.2018.527

Abstract

PURPOSE
Mismatch repair (MMR) deficiency plays a critical role in rectal cancer. This study aimed to explore the associations between genetic variations in seven MMR genes and adverse events (AEs) and survival of patients with rectal cancer treated with postoperative chemoradiotherapy (CRT).
MATERIALS AND METHODS
Fifty single nucleotide polymorphisms in seven MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) genes were genotyped by Sequenom MassARRAY method in 365 patients with locally advanced rectal cancer receiving postoperative CRT. The associations between genotypes and AEs were measured by odds ratios and 95% confidence intervals (CIs) by unconditional logistic regression model. The associations between genetic variations and survival were computed by the hazard ratios and 95% CIs by Cox proportional regression model.
RESULTS
The most common grade ≥ 2 AEs in those 365 patients, in decreasing order, were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). Except 38 cases missing, 61 patients (18.7%) died during the follow-up period. We found MSH3 rs12513549, rs33013 and rs6151627 significantly associated with the risk of grade ≥ 2 diarrhea. PMS1 rs1233255 had an impact on the occurrence of grade ≥2 dermatitis. Meanwhile, PMS1 rs4920657, rs5743030, and rs5743100 were associated with overall survival (OS) time of rectal cancer.
CONCLUSION
These results suggest that MSH3 and PMS1 polymorphisms may play important roles in AEs prediction and prognosis of rectal cancer patients receiving postoperative CRT, which can be potential genetic biomarkers for rectal cancer personalized treatment.

Keyword

Rectal neoplasms; Single nucleotide polymorphism; DNA mismatch repair; Chemoradiotherapy; Acute adverse event; Survival

MeSH Terms

Biomarkers
Chemoradiotherapy*
Dermatitis
Diarrhea
DNA Mismatch Repair*
Follow-Up Studies
Genetic Variation*
Genotype
Humans
Leukopenia
Logistic Models
Methods
Odds Ratio
Polymorphism, Single Nucleotide
Prognosis
Rectal Neoplasms*
Biomarkers

Figure

• 

  Fig. 1. Kaplan-Meier estimates of three single nucleotide polymorphisms and overall survival time in patients with rectal cancer receiving postoperative chemoradiotherapy. (A) rs4920657 (log-rank test, p=0.087). (B) rs5743030 (log-rank test, p=0.025). (C) rs5743100 (log-rank test, p=0.075).

Reference

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