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.

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.

• Authors: Jie Yang, Ying Huang, Yanru Feng, Hongmin Li, Ting Feng, Jinna Chen, Luxi Yin, Weihu Wang, Shulian Wang, Yueping Liu, Yongwen Song, Yexiong Li, Jing Jin, Wen Tan, Dongxin Lin
• Journal: Cancer research and treatment (Cancer Res Treat) Vol. 51 Issue 3 Pg. 1198-1206 (Jul 2019) ISSN: 2005-9256 [Electronic] Korea (South)
• PMID: 30590005 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• MSH3 protein, human
• MutS Homolog 3 Protein
• Neoplasm Proteins
• PMS1 protein, human
• MutL Proteins

Topics

• Biomarkers, Tumor (genetics)
• Chemoradiotherapy, Adjuvant (adverse effects)
• Female
• Genetic Association Studies
• Humans
• Male
• MutL Proteins (genetics)
• MutS Homolog 3 Protein (genetics)
• Neoplasm Proteins (genetics)
• Polymorphism, Single Nucleotide
• Precision Medicine
• Prognosis
• Rectal Neoplasms (genetics, mortality, therapy)
• Sequence Analysis, DNA
• Survival Analysis
• Treatment Outcome