Association of XRCC1 Arg399Gln Polymorphism with Colorectal Cancer Risk: A HuGE Meta Analysis of 35 Studies

Forat-Yazdi, Mohammad; Gholi-Nataj, Mohsen; Neámatzadeh, Hossein; Nourbakhsh, Parisa; Shaker-Ardakani, Hossein

doi:10.7314/apjcp.2015.16.8.3285

Cited by 19 publications

(15 citation statements)

References 43 publications

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“…The XRCC1 gene is a DNA-repair gene that encodes a protein that plays a major role in single-strand break repair and base excision repair systems. A recent large-scale meta-analysis confirmed the presence of a significant link between XRCC1 399Arg/Gln polymorphism and the development of CRC [13].…”

Section: Discussionmentioning

confidence: 93%

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

et al. 2017

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Objective: The objectives of this study were to evaluate the impact of two X-ray repair cross complementing 1 (XRCC1) gene polymorphisms (Arg194Trp and Arg399Gln) on the risk of development of colorectal cancer (CRC) and to assess the expression levels of microRNA-21 (miR-21) in CRC patients. Materials and Methods:A case-control cross sectional study was conducted on 50 CRC patients and 50 cancer-free subjects. DNA and miR-21 were extracted from whole blood samples. The expression levels of the XRCC1 polymorphisms and miR-21 were assessed by real-time PCR in all subjects of the study.Results: Genotype analysis revealed a significant association between CRC risk and both the Arg194Trp genotype (OR=11.407, 95% CI=4.039-32.221, p<0.001) and the Arg399Gln genotype (OR=3.778, 95% CI= 1.6-8.919, p=0.002). The expression levels of circulating miR-21 were able to detect CRC cases significantly (p=0.022) with a sensitivity of 82% and a specificity of 56% (Area under the curve (AUC)=0.633) but were unable to distinguish between early and late cases (AJCC classification) (p=0.194). Conclusion:The XRCC1 Arg194Trp and Arg399Gln polymorphisms both confer high susceptibility for the development of CRC. Circulating miR-21 expression levels are a potentially diagnostic non-invasive genetic marker of CRC.Keywords: Colorectal cancer, miRNA-21, XRCC1, DNA repair, single nucleotide polymorphisms ÖZ Amaç: Bu çalışmanın amacı iki XRCC1 gen polimorfizminin (Arg194Trp ve Arg399Gln) kolorektal kanser (KRK) gelişimi riski üzerindeki etkisini değerlendirmek ve KRK hastalarında microRNA-21 (miR-21) ekspresyonu düzeylerini incelemektir.Gereç ve Yöntemler: 50 KRK hastası ve 50 kansersiz denekle vaka-kontrollü bir kesitsel çalışma gerçekleşti-rildi. Tüm kan numunelerinden DNA ve miR-21 alındı. XRCC1 polimorfizmlerinin ve miR-21'in ekspresyon seviyeleri, çalışmadaki tüm deneklerde gerçek zamanlı PCR ile değerlendirildi. Bulgular: Genotip analizinde KRK riski ile Arg194Trp (OR=11.407, 95% CI=4.039-32.221, p<0,001) ve Arg399Gln (OR=3.778, 95% CI=1, p=0,002) genotipleri arasında önemli bir ilişki ortaya konuldu. Dolaşımdaki miR-21 ekspresyon düzeyleriyle KRK olguları %82 duyarlılık ve %56 özgüllük (AUC=0,633) ile anlamlı bir şekilde (p=0,022) saptanabildi, ancak erken ve geç vakalar ayırt edilemedi (AJCC sınıflandırması) (p=0,194).Sonuç: XRCC1 Arg194Trp ve Arg399Gln polimorfizmlerinin her ikisi de KRK gelişimine yüksek düzeyde yatkınlık göstermektedir. Dolaşımdaki miR-21 ekspresyon seviyeleri potansiyel olarak KRK'nın tanısal noninvasiv genetik belirtecidir.Anahtar Kelimeler: Kolorektal kanser, miRNA-21, XRCC1, DNA onarımı, SNPs Eurasian J Med 2017; 49: 132-6 Original Article

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Section: Discussionmentioning

confidence: 93%

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

et al. 2017

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“…studies in which distribution of genotype in controls deviated significantly from the Hardy–Weinberg equilibrium) were excluded, the increased risk association remained statistically significant based on data from 22 studies involving 6149 cases and 10 167 controls. To address this inconsistency, a more thorough HuGE meta‐analysis of 35 studies (involving 9114 cases and 13 948 controls) was performed with a more stringent inclusion criteria and the results obtained concurred with that an increased colorectal cancer risk was observed for the variant allele . Overall, the lack of significant risk association of the XRCC1 c.580C>T (p.Arg194Trp) and c.839G>A (p.Arg280His) polymorphisms makes them unsuitable to be used as a predisposition biomarker for colorectal cancer, whereas it is conceivable to suggest the potential use of the c.1196A>G (p.Gln399Arg) polymorphism as a predictive biomarker for colorectal cancer predisposition.…”

Section: Dna Repair Genesmentioning

confidence: 95%

“…To address this inconsistency, a more thorough HuGE meta-analysis of 35 studies (involving 9114 cases and 13 948 controls) was performed with a more stringent inclusion criteria and the results obtained concurred with that an increased colorectal cancer risk was observed for the variant allele. 77 Overall, the lack of significant risk association of the XRCC1 c.580C>T (p.Arg194Trp) and c.839G>A (p.…”

Section: Mutyhmentioning

confidence: 98%

Low penetrance genetic polymorphisms as potential biomarkers for colorectal cancer predisposition

Tan

2018

The Journal of Gene Medicine

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Colorectal cancer is a leading form of cancer in both males and females. Early detection of individuals at risk of colorectal cancer allows proper treatment and management of the disease to be implemented, which can potentially reduce the burden of colorectal cancer incidence, morbidity and mortality. In recent years, the role of genetic susceptibility factors in mediating predisposition to colorectal cancer has become more and more apparent. Identification of high-frequency, low-penetrance genetic polymorphisms associated with the cancer has therefore emerged as an important approach which can potentially aid prediction of colorectal cancer risk. However, the overwhelming amount of genetic epidemiology data generated over the past decades has made it difficult for one to assimilate the information and determine the exact genetic polymorphisms that can potentially be used as biomarkers for colorectal cancer. This review comprehensively consolidates, based primarily on results from meta-analyses, the recent progresses in the search of colorectal cancer-associated genetic polymorphisms, and discusses the possible mechanisms involved.

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“…[7][8][9] Thus, various hypothesis-driven case-control studies have been carried out to evaluate the association between the risk of sporadic colorectal cancer and polymorphisms within candidate genes such as OGG1, APEX, POLB, XRCC1 and MUTYH (base excision repair [BER]), ERCC1, ERCC2, XPC and ERCC5 (nucleotide excision repair [NER]), XRCC2 and XRCC3 (double-strand breaks repair [DSB]) and poly(ADP-ribose) polymerase (PARP). 9,10 Positive associations were described for single-nucleotide polymorphisms (SNPs) within APEX, ERCC1, MUTYH, OGG1, XPC, XPG, XRCC1 and XRCC3 genes, [11][12][13][14][15][16] but some results were either discordant or not replicated 9,11,[16][17][18][19] likely as the consequence of a limited statistical power. Genome-wide association studies (GWAS) could not confirm most of the positive associations within the DNA repair genes previously described.…”

Section: Introductionmentioning

confidence: 99%

DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility

Pardini

Corrado

Paolicchi

et al. 2019

Intl Journal of Cancer

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Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p‐value = 3.5 × 10−6) and rs2189517 (in RAD51B) with rectal cancer risk (p‐value = 5.7 × 10−6). The results had statistical significance close to the Bonferroni corrected p‐value of 5.8 × 10−6. Ninety‐four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis‐eQTL suggesting possible mechanisms of carcinogenesis.

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Association of XRCC1 Arg399Gln Polymorphism with Colorectal Cancer Risk: A HuGE Meta Analysis of 35 Studies

Cited by 19 publications

References 43 publications

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

Low penetrance genetic polymorphisms as potential biomarkers for colorectal cancer predisposition

DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility

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