Investigation of methylenetetrahydrofolate reductase tagging polymorphisms with colorectal cancer in Chinese Han population.

Sheng Zhang,Yu Chen,Mingqiang Kang,Chao Liu,Weifeng Tang,Shuchen Chen,Hao Qiu,Yafeng Wang

doi:10.18632/oncotarget.18845

Abstract

The aim of this case-control study was to assess the relationship between the tagging polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene and the susceptibility to colorectal cancer (CRC) in a Chinese Han population. A custom-by-design 48-Plex SNPscan Kit was used to determine the genotypes of MTHFR rs3753584 T>C, rs9651118 T>C, rs1801133 G>A, rs4846048 A>G and rs4845882 G>A polymorphisms in 387 CRC patients and 1,536 non-cancer controls. The results revealed that MTHFR rs1801133 G>A polymorphism was associated with a decreased risk of overall CRC. While MTHFR rs4845882 G>A polymorphism conferred an increased risk to overall CRC. In a stratified analysis by CRC region, we found MTHFR rs3753584 T>C and rs9651118 T>C polymorphisms were associated with the increased risk of colon cancer. In addition, a significantly increased risk of rectum cancer associated with MTHFR rs3753584 T>C polymorphism was overt. However, MTHFR rs1801133 G>A polymorphism conferred a decreased risk to colon cancer. In conclusion, findings of the present study reveal that the tagging polymorphisms in MTHFR gene (rs3753584 T>C, rs9651118 T>C and rs4845882 G>A) are associated with the increased risk of CRC. However, MTHFR rs1801133 G>A polymorphism confers a decreased risk to CRC. Additional studies with larger sample size are needed to confirm these findings.

Highlights

Colorectal cancer (CRC) is the fourth most frequent type of malignancy among females and the fifth most frequent type among males in China, accounting for160,600 and 215,700 cases in 2015, respectively [1]
For methylenetetrahydrofolate reductase (MTHFR) rs3753584 T>C polymorphism, we found this polymorphism was associated with an increased risk of rectum cancer (CC+TC vs. TT: adjusted odds ratios (ORs) = 1.44, 95% confidence intervals (CIs) = 1.04–2.00, P = 0.026; TC vs. TT: adjusted OR = 1.44, 95% CI = 1.04– 2.00, P = 0.030) and of colon cancer (CC vs. TT+TC: adjusted OR = 3.74, 95% CI = 1.31–10.64, P = 0.014; CC vs. TT: adjusted OR = 3.63, 95% CI = 1.27–10.38, P = 0.016)
For MTHFR rs9651118 T>C polymorphism, we found MTHFR rs9651118 CC genotypes might be associated with an increased risk of colon cancer (CC vs. TT+TC: adjusted OR = 1.53, 95% CI = 1.01–2.31, P = 0.044)

Summary

Introduction

Colorectal cancer (CRC) is the fourth most frequent type of malignancy among females and the fifth most frequent type among males in China, accounting for160,600 and 215,700 cases in 2015, respectively [1]. The CRC morbidity is shooting up in developing countries including China [1, 2]; CRC etiology remains unknown Risk factors, such as advanced age, family history of CRC, benign adenomatous polyp, www.impactjournals.com/oncotarget inflammatory bowel disease, drinking, smoking, being physically inactive, low intake of fruits and vegetables and high intake of dietary fat, may play important roles in the occurrence and the development of CRC [3,4,5,6,7,8,9]. The presence of the long induction period between reduced risk of CRC and adequate folate status is evident in both epidemiologic and molecular mechanistic studies [14]. DNA strand break and repair, and impaired DNA methylation have been associated with folate deficiency and CRC

Methods

Results

Conclusion