His595Tyr polymorphism in the methionine synthase reductase (MTRR) gene is associated with pancreatic cancer risk
- Shumpei Ohnami 1, Yasunori Sato , Kimio Yoshimura , Sumiko Ohnami , Hiromi Sakamoto , Kazunori Aoki , Hideki Ueno , Masafumi Ikeda , Chigusa Morizane , Kazuaki Shimada , Yoshihiro Sakamoto , Minoru Esaki , Ikuo Saito , Hiroshi Hirose , Daizo Saito , Haruhiko Sugimura , Tomoo Kosuge , Takuji Okusaka , Teruhiko Yoshida
- 1Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
- 0Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
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View abstract on PubMed
Summary
This summary is machine-generated.This study identifies a common missense single nucleotide polymorphism (SNP) in the MTRR gene as a novel risk factor for pancreatic cancer. This finding has functional implications for folate metabolism and genome methylation.
Area Of Science
- Genetics
- Cancer Biology
- Molecular Epidemiology
Background
- Pancreatic cancer, particularly invasive ductal adenocarcinoma, has a complex genetic predisposition.
- Gene-environment interactions are crucial in carcinogenesis, but their role in pancreatic cancer is not fully understood.
Purpose Of The Study
- To investigate the genetic predisposition to sporadic invasive ductal adenocarcinoma of the pancreas.
- To focus on genes involved in gene-environment interactions relevant to pancreatic cancer development.
Main Methods
- Genotyping of 227 single nucleotide polymorphisms (SNPs) in 46 genes among 198 cases and 182 controls.
- Joint analysis of significant SNPs with expanded sample sizes (317 cases vs. 1232 controls).
- High-density SNP typing, haplotype analysis (702 cases vs. 785 controls), and functional assessment of MTRR gene variants using transfected cells.
Main Results
- Two SNPs in the methionine synthase reductase (MTRR) gene, rs162049 and rs10380, were significantly associated with pancreatic cancer risk (P < .0018 and P < .0063, respectively).
- These associations remained significant after multiple testing adjustment and permutation tests.
- Functional studies revealed that risk haplotypes of MTRR were associated with elevated homocysteine, reduced LINE-1 methylation, and lower MTRR protein expression.
Conclusions
- A common missense SNP in the MTRR gene is identified as a novel susceptibility factor for pancreatic cancer.
- The MTRR gene plays a functional role in folate metabolism and influences genome-wide methylation status, contributing to pancreatic cancer risk.
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