Iiyal Amuthan, I C (2011) Association of DNA repair gene polymorphisms with carcinoma prostate. Masters thesis, Madras Medical College, Chennai.
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Abstract
INTRODUCTION : Prostate cancer is the most common noncutaneous malignancy in men in the United States. In India, the incidence is relatively less. Risk of disease varies most prominently with age, ethnicity, family history, and diet . A strong family history indicative of a highly penetrant prostate cancer gene is believed to account for only 5–10% of prostate cancers, whereas a larger percentage of prostate cancers may be due to common polymorphisms in genes giving rise to a low penetrance risk of disease. Malignant transformation of prostate cells is accompanied by somatic genomic changes, including deletions, amplifications, and point mutations. In vitro studies of human prostate tissue have demonstrated that DNA adducts form in prostate tissue after exposure to environmental toxins. Moreover, intake of antioxidants via the diet or as supplements may decrease prostate cancer risk through the inactivation of reactive oxygen species, thereby protecting the DNA from oxidative damage. This evidence suggests that DNA repair capacity may play an important role in prostate carcinogenesis, but little is known about what direct effect DNA repair capacity has on prostate cancer risk. The XPD gene codes for a DNA helicase involved in transcription and nucleotide excision repair. Mutations in the XPD gene can completely prevent DNA opening and dual incision, steps that lead to the repair of DNA adducts. The DNA repair function of XPD is critical to reparation of genetic damage from tobacco and other carcinogens. Several common single bp substitution polymorphisms in the XPD gene have been identified. AIM AND OBJECTIVES : The aim of the study is to determine the risk attributed by polymorphisms in genes regulating the DNA Repair pathway with reference to the Xray repair Cross complementary 1 gene (XRCC1) and Xeroderma pigmentosum group D gene (XPD ) with Carcinoma Prostate. The study also aims to perform a stratified analysis of the genotypes with Age, Gleason sum and Serum PSA levels of Prostate Cancer patients. MATERIAL AND METHODS : The age of the subjects included in the study ranged from 55 to 87 years. The cases and controls were similar in ethnicity and nutritional status. Clinical characteristics, including Gleason score, PSA, and tumor stage were obtained from the patients. The controls were healthy, unrelated individuals with normal serum PSA levels, normal digital rectal examination. CONCLUSION : The XRCC 1 Arg/Gln genotype and XPD Lys/Gln genotype were significantly associated with an increased risk of developing Prostate cancer. The XRCC 1 and XPD genotypes stratified by age, grade and Sr.PSA levels did not show any significant risk of developing Prostate cancer. The present study of DNA Repair gene polymorphisms predicts risk of developing Prostate cancer and would enable identification of genetically predisposed individuals.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | Association ; DNA repair gene polymorphisms ; carcinoma prostate. |
| Subjects: | MEDICAL > Urology |
| Depositing User: | Kambaraman B |
| Date Deposited: | 10 Aug 2017 02:20 |
| Last Modified: | 10 Aug 2017 03:15 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/2543 |
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