A Haplotype Variation Affecting the Mitochondrial Transportation of HMYH Protein Could Be a Risk Factor for Colorectal Cancer in Chinese

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2008 Sep 25

PMID 18811933

Citations 9

Authors

Huimei Chen

Lizhi Xu

Qiufeng Qi

Yanweng Yao

Ming Zhu

Yaping Wang

Affiliations

Soon will be listed here.

Abstract

Background: The human MutY homolog (hMYH), a DNA glycolsylase involved in the excision repair of oxidative DNA damage, is currently studied in colorectal cancer (CRC). We previously demonstrated a haplotype variant c.53C>T/c.74G>A of hMYH (T/A) increasing the risk for gastric cancer in Chinese. However, most investigations on correlation between hMYH and CRC are conducted in Western countries and the underlying mechanism has been poorly understood.

Methods: To determine whether the haplotype T/A variant of hMYH was related to colorectal carcinogenesis, we performed a case-control study in 138 colorectal cancer (CRC) patients and 343 healthy controls in a Chinese population. Furthermore, the C/G for wild-type, C/A or T/G for single base variant and T/A for haplotype variant hMYH cDNAs with a flag epitope tag were cloned into pcDNA3.1+ vector and transfected into cos-7 cell line. Their subcellular localizations were determined by immunofluorescence assay.

Results: It was found that the frequency of haplotype variant allele was statistically higher in CRC patients than that in controls (P = 0.02, odds ratio = 5.06, 95% confidence interval = 1.26 - 20.4). Similarly, significant difference of heterozygote frequency was indicated between the two groups (P = 0.019), while no homozygote was found. In addition, immunofluorescence analysis showed that hMYH protein with haplotype T/A variation presented in both nucleus and mitochondria, in contrast to the wild-type protein only converging in mitochondria. However, neither of the single missense mutations alone changed the protein subcelluar localization.

Conclusion: Although preliminarily, these results suggest that: the haplotype variant allele of hMYH leads to a missense protein, which partly affects the protein mitochondrial transportation and results as nuclear localization. This observation might be responsible for the increased susceptibility to cancers, including CRC, in Chinese.

Citing Articles

Germline Profiling and Molecular Characterization of Early Onset Metastatic Colorectal Cancer.

Xu T, Zhang Y, Zhang J, Qi C, Liu D, Wang Z Front Oncol. 2020; 10:568911.

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Association of monoallelic MUTYH mutation among Egyptian patients with colorectal cancer.

Elsaid A, Elshazli R, El-Tarapely F, Darwish H, Abdel-Malak C Fam Cancer. 2016; 16(1):83-90.

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MUTYH Gene Polymorphisms as Risk Factors for Rheumatoid Arthritis.

Kung Y, Tsai K, Huang C, Lin H, Chen T, Hsu Y Biomed Res Int. 2015; 2015:893796.

PMID: 26273655 PMC: 4530216. DOI: 10.1155/2015/893796.

Increased risk for colorectal adenomas and cancer in mono-allelic MUTYH mutation carriers: results from a cohort of North-African Jews.

Rosner G, Bercovich D, Daniel Y, Strul H, Fliss-Isakov N, Ben-Yehoiada M Fam Cancer. 2015; 14(3):427-36.

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Effect of MPG gene rs2858056 polymorphism, copy number variation, and level of serum MPG protein on the risk for rheumatoid arthritis.

Huang C, Chen S, Huang P, Tsai F PLoS One. 2015; 10(3):e0120699.

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