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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...

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Main Author: Noor Hanis Abu Halim
Format: Thesis
Language:English
English
Published: 2013
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RC254-282 Neoplasms. Tumors. Oncology Including cancer and carcinogens
Online Access:https://eprints.ums.edu.my/id/eprint/42827/1/24%20PAGES.pdf
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spelling my.ums.eprints.428272025-02-24T01:31:27Z https://eprints.ums.edu.my/id/eprint/42827/ Genetic polymorphisms of XRCC1 gene in gastrointestinal cancer among Sabah population Noor Hanis Abu Halim RC254-282 Neoplasms. Tumors. Oncology Including cancer and carcinogens 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. 2013 Thesis NonPeerReviewed text en https://eprints.ums.edu.my/id/eprint/42827/1/24%20PAGES.pdf text en https://eprints.ums.edu.my/id/eprint/42827/2/FULLTEXT.pdf Noor Hanis Abu Halim (2013) Genetic polymorphisms of XRCC1 gene in gastrointestinal cancer among Sabah population. Masters thesis, Universiti Malaysia Sabah.
institution Universiti Malaysia Sabah
building UMS Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Sabah
content_source UMS Institutional Repository
url_provider http://eprints.ums.edu.my/
language English
English
topic RC254-282 Neoplasms. Tumors. Oncology Including cancer and carcinogens
spellingShingle RC254-282 Neoplasms. Tumors. Oncology Including cancer and carcinogens
Noor Hanis Abu Halim
Genetic polymorphisms of XRCC1 gene in gastrointestinal cancer among Sabah population
description 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.
format Thesis
author Noor Hanis Abu Halim
author_facet Noor Hanis Abu Halim
author_sort Noor Hanis Abu Halim
title Genetic polymorphisms of XRCC1 gene in gastrointestinal cancer among Sabah population
title_short Genetic polymorphisms of XRCC1 gene in gastrointestinal cancer among Sabah population
title_full Genetic polymorphisms of XRCC1 gene in gastrointestinal cancer among Sabah population
title_fullStr Genetic polymorphisms of XRCC1 gene in gastrointestinal cancer among Sabah population
title_full_unstemmed Genetic polymorphisms of XRCC1 gene in gastrointestinal cancer among Sabah population
title_sort genetic polymorphisms of xrcc1 gene in gastrointestinal cancer among sabah population
publishDate 2013
url 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/
_version_ 1825161825815101440
score 13.244413

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