Genetic polymorphisms of XRCC1 gene in gastrointestinal cancer among Sabah population
Gastrointestinal cancer is a common cancer causing high mortality worldwide. One of the factors causing gastrointestinal cancer is genetic. X-ray cross complementing group 1 (XRCC1) gene which is one of the DNA repair genes play important role in base excision repair process. Polymorphisms of this g...
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis |
| Language: | English English |
| Published: |
2013
|
| Subjects: | |
| Online Access: | https://eprints.ums.edu.my/id/eprint/42827/1/24%20PAGES.pdf https://eprints.ums.edu.my/id/eprint/42827/2/FULLTEXT.pdf https://eprints.ums.edu.my/id/eprint/42827/ |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Gastrointestinal cancer is a common cancer causing high mortality worldwide. One of the factors causing gastrointestinal cancer is genetic. X-ray cross complementing group 1 (XRCC1) gene which is one of the DNA repair genes play important role in base excision repair process. Polymorphisms of this gene are thought to affect its functions in repairing the damaged DNA bases. The objective of this study is to explore the risk of XRCC1 polymorphisms towards upper and lower gastrointestinal cancers and to investigate the influence of other factors towards the risk of cancer. A total of 182 gastrointestinal cancer cases and 861 healthy controls were recruited for this study from year 2009-2011. Peripheral blood was obtained and DNA was extracted from the blood and analysed for both polymorphisms of XRCC1 gene at codon 194 and 399 using PCR-RFLP approach. Restriction enzyme Pvu II and Nci I were used to detect wild-type and variant form of XRCC1 gene at codon 194 and codon 399, respectively. Statistical analysis was carried out to determine the association of the XRCC1 polymorphisms towards upper and lower gastrointestinal cancer risks. For Arg194Trp polymorphism, the frequency of variant allele was higher in both upper and lower gastrointestinal cancers (0.27 and 0.26, respectively) compared to controls (0.18). For Arg399Gln polymorphism, the frequency of variant allele was slightly higher in controls (0.38) compared to upper and lower gastrointestinal cancers (0.37 and 0.34, respectively). For Arg194Trp polymorphism, those with Arg/Trp and Trp/Trp genotypes had significantly increased risk in upper gastrointestinal cancer by 1.8-fold and 3.8-fold, respectively (OR=1.77, 95% CI: 1.05-3.00, p= 0.031 and OR= 3.80, 95% CI: 1.04-13.89, p=0.031) compared to Arg/Arg genotype. Likewise, for lower gastrointestinal cancer, the risk of this cancer was significantly increased by 1.8-fold in those with Arg/Trp genotype (OR= 1.79, 95% CI: 1.21-2.66, p=0.003), but not in those with Trp/Trp genotype. Variant genotypes of Arg399Gln polymorphism showed non-significantly reduced risk in lower gastrointestinal cancer whereas in upper gastrointestinal cancer, no association was shown. These findings suggest that Arg194Trp polymorphism impose risk to both upper and lower gastrointestinal cancers in Malaysian but not Arg399Gln polymorphism. Combined effect of these 2 putative high risk genotypes (CT and GA) and (TT and GG) increased significantly risk of upper gastrointestinal cancer by 2.5-fold and 5.4-fold, respectively (OR= 2.54, 95% CI: 0.1.07-5.98; p=0.029 and OR= 5.39, 95% CI: 1.28-22.80, p= 0.011), compared to those with combination of CC and GG genotypes. Combination effect of these genotypes showed non-statistically significant association in lower gastrointestinal cancer. After adjustment for age, gender and ethnicities, CT genotype was associated with significantly increased risk of lower gastrointestinal cancer (OR= 1.66, 95% CI: 1.06-2.60, p= 0.027) and upper gastrointestinal cancer (OR= 1.98, 95% CI: 1.07-3.65, p= 0.029) whereas TT genotype were non-significantly increased risk of both upper and lower gastrointestinal cancers. For Arg399Gln polymorphism, after adjustment with age, gender and ethnicities, GA and AA genotypes increased non-significantly the risk of upper gastrointestinal cancer and no association was shown in lower gastrointestinal cancer. |
|---|