Title page for etd-0825111-020128


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URN etd-0825111-020128
Author Liang Ming Yen
Author's Email Address No Public.
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Department Biological Sciences
Year 2010
Semester 2
Degree Master
Type of Document
Language English
Title The Association of XRCC1 Polymorphisms with Development and Prognosis of Oral and Pharyngeal Squamous Cell Carcinomas
Date of Defense 2011-07-13
Page Count 102
Keyword
  • prognosis
  • polymorphism
  • XRCC1
  • risk
  • OPSCC
  • oral cancer
  • Abstract X-ray repair cross complementing Group 1 (XRCC1) protein plays an important role in base excision repair. Single nucleotide polymorphisms (SNPs) in XRCC1 gene may affect DNA repairing ability, genetic susceptibility, and prognosis to oral and pharyngeal squamous cell cancer (OPSCC). This study was carried out to evaluate the association of three XRCC1 SNPs with the risk and prognosis of OPSCC. A total of 509 OPSCC cases and 678 cancer-free controls were recruited to detect the genotypes of XRCC1 by PCR-RFLP. Then, 447 case patients with surgical treatment and safety margins were included in the survival analysis. No association was observed for XRCC1 194 and the risk of OPSCC. As compared with the wild Arg/Arg genotype, the combined genotypes of 280 Arg/His and His/His were with decreased risk (AOR=0.73, 95% CI, 0.52-1.03, p = 0.069) of OPSCC and with a significantly decreased risk (AOR=0.67, 95% CI, 0.47-0.97, p = 0.035) of oral cavity. As compared with the Arg/Arg genotype of XRCC1 399, the Gln/Gln genotype was with the increased risk of OPSCC (AOR=2.06, 95%CI: 1.21-3.51, p = 0.008) and oral cavity cancer (AOR=1.89, 95%CI: 1.08-3.33, p = 0.026). We defined the “putative high risk haplotypes” as “Arg-Arg-Gln and Trp-Arg-Gln”. The AOR were 1.29 (95% CI, 1.04-1.60, p = 0.020) for the “putative high risk haplotypes” as compared with other haplotypes for OPSCC. Then, two putative high risk haplotypes were combined into “putative high risk diplotypes”. The AOR for the “high risk diplotypes” were 1.98 (95% CI, 1.18-3.33, p = 0.010) as compared with other diplotypes for OPSCC. No association between XRCC1 polymorphisms and clinicopathological outcomes, except XRCC1 280. Those carriers of XRCC1 280His allele (combined Arg/His and His/His genotypes) were associated with late onset (≥50 yrs) of oral cavity cancers. No association between genetic variants in XRCC1 and disease-specific survival except XRCC1 399. Patients with 399 Arg/Gln and Gln/Gln genotypes showed a significant better survival as compared to Arg/Arg genotype carriers (AHR 0.41 95% CI: 0.18-0.93), especially for those patients younger than 50 years (p = 0.012), in pathological stage III or IV (p = 0.044), and without postoperative radiotherapy (p = 0.012). In summary, XRCC1 280 Arg/His and His/His genotypes were associated with decreased risk of oral cavity cancer. 399 Gln/Gln genotype was associated with increased risk of OPSCC and oral cavity cancer. The putative “high risk haplotypes and diplotypes” were with increased risk of OPSCC. However, 399 Arg/Gln and Gln/Gln genotypes were prognostic factors, especially for those with young age, aggressive tumor stage, and without postoperative radiotherapy for oro and hypopharynx patients. These findings suggest that XRCC1 polymorphisms may play a role in the development and prognosis of OPSCC.
    Advisory Committee
  • Cho, Chung-Lung - chair
  • Shiue, Yow-Ling - co-chair
  • Luo-Ping Ger - advisor
  • Cheng, Jiin-Tsuey - advisor
  • Files
  • etd-0825111-020128.pdf
  • Indicate in-campus at 5 year and off-campus access at 5 year.
    Date of Submission 2011-08-25

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