Trial Information

DNA repair plays a key role in carcinogenesis through the removal and repair of DNA damage
induced by endogenous and environmental sources. The DNA repair system included four
pathways: 1) Base Excision Repair (BER), 2) Nucleotide Excision Repair (NER), 3) Mismatch
Repair (MMR) and 4) Double-Strand Break Repair, including homologous recombination pathway
and nonhomologous end-joining repair pathway. Decreased and impaired DNA repair capacity has
been reported in various cancers, however, its effect on prostate cancer still under
investigated.

Common polymorphisms in DNA repair gene may alter protein function and individual’s capacity
to repair damaged DNA, hence, influence the cancer susceptibility. Polymorphic variants of
DNA repair gene have been found to be associated with cancer susceptibility, but rare
studies have investigated their effect on prostate cancer. Since variation in the function
of these DNA repair genes also impact a cancer cell’s viability or resistance to treatment,
genetic variants in DNA repair might serve as a valuable biomarker in forcasting the result
of cancer treatment. In fact, some reports have demonstrated the association between
polymorphisms of DNA repair genes and results of treatment of various cancers.

For the present study proposal, we focused on several DNA repair genes: X-ray repair cross-
complementing group 1 (XRCC1), human oxoguanine glycosylase I (hOGG1), xeroderma pigmentosum
complementation group D (XPD), hMSH2, hMLH1 and X-ray repair cross-complementing group 3
(XRCC3), which might have relevance in prostate carcinogenesis based on their known
functions. XRCC1 is involved in DNA repair in the base excision pathway, the hOGG1 gene
encodes a DNA glycosylase /apurinic-apyrimidinic lyase that catalyzes the excision and
removal the 8-OH-dG (8-hydroxy- 2-deoxyguanine) - which is a major form of oxidative DNA
damage. The XPD gene codes for a DNA helicase involved in transcription and nucleotide
excision repair. The hMSH2 and hMLH1 are genes involved with mismatch repair. The XRCC3 gene
encoded a protein in the double-strand break homologous recombinational repair pathways.

In this proposed study, we will also use PCR-based methods to investigate the effects of DNA
repair gene polymorphisms on prostate cancer susceptibility, pathological grade, disease
stage and clinical outcome. With these efforts, we will further understand the association
between DNA repair gene polymorphism and prostate cancer and provided important information
for screening, prevention and treatment of prostate cancer.