Abstract
Purpose
Oxidative stress is considered a risk factor for prostate cancer development and is associated with the production of reactive oxygen species (ROS). The base excision repair gene MYH protects against ROS-mediated damage to DNA. Inherited MYH mutations predispose to colorectal adenomas and cancer. A compromised base-excision repair function due to defective MYH may contribute to prostate carcinogenesis. Here, we examine the genetic contribution of MYH to prostate cancer risk.
Methods
Patients diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN) alone (n = 45), prostate cancer alone (n = 123) or both (n = 82) were screened for the two most common mutations in the MYH gene using PCR-based RFLP analysis. A single patient with an inherited MYH mutation as well as a subset of 26 patients presenting with a family history of colorectal cancer were screened for additional MYH mutations by direct sequencing of the entire coding region.
Results
Biallelic germline mutations in MYH were not detected among prostate cancer patients. Only a single patient was a heterozygous carrier for the Y165C missense mutation. Allelic deletion or somatic mutation of the remaining MYH allele was not identified in this patient’s tumor DNA. Two patients harbored V22M polymorphism and three patients were carriers of Q324H polymorphism.
Conclusions
MYH mutations are unlikely to contribute to prostate cancer risk.
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Acknowledgments
We thank all patients who participated in this study. Grant sponsor: this research is supported by the Canadian Prostate Cancer Research Initiative (B.B. and N.F.; CPCRI IDEA Grant #015474).
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Shin, EJ., Chappell, E., Pethe, V. et al. MYH mutations are rare in prostate cancer. J Cancer Res Clin Oncol 133, 373–378 (2007). https://doi.org/10.1007/s00432-006-0181-x
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DOI: https://doi.org/10.1007/s00432-006-0181-x