Arg399Gln polymorphism of XRCC1 gene and risk of colorectal cancer in Kashmir: A case control study

Nissar, Saniya; Lone, Tufail Ahmad; Banday, Mujeeb Zafar; Rasool, Roohi; Chowdri, Nissar A.; Parray, Fazl Q.; Abdullah, Safiya; Sameer, Aga Syed

doi:10.3892/ol.2013.1104

Cited by 28 publications

(25 citation statements)

References 24 publications

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“…Further, correlation for gender group versus stage of the disease-(stage III and Stage IV) with genotypes; we found no significance with this association between these parameters. This data were consistent with earlier reports on risk of cancer of the breast (Duell et al, 2001), bladder and lung (Ratnasinghe et al, 2001), thyroid carcer (Fard-Esfahani et al, 2011), bladder cancer (Mao et al, 2013), and colorectal cancer (Nissar et al, 2013). It is therefore obvious that XRCC1 codon 399 may be associated with altered function of the coding products and thus contribute to the individual's genetic susceptibility to lung cancer.…”

supporting

confidence: 91%

The Codon 399 Arg/Gln XRCC1 Polymorphism is Associated with Lung Cancer in Indians

Natukula¹,

Jamil²,

Pingali³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair) pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene (at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility. Materials and Methods: We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed. Results: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%), and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Gln genotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenario where Arg399Gln genotypes were found to be associated with stage of the disease in females. Conclusions: It is concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients with smoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lung cancer for diagnosis and prognosis.

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supporting

confidence: 91%

The Codon 399 Arg/Gln XRCC1 Polymorphism is Associated with Lung Cancer in Indians

Natukula¹,

Jamil²,

Pingali³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Another study conducted by Nissar et al [18] among a Kashmiri population found a significant impact of the Trp/Trp and Arg/Trp genotypes on the development of CRC.…”

Section: Discussionmentioning

confidence: 99%

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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“…Previous studies reported that the heterozygous (399Arg/Gln) and variant (399Gln/Gln) genotypes of this SNP were significant risk factor for GIC in different populations including in Han Chinese for liver, gastric and colorectal cancers (Shen et al, 2000;Pan et al, 2011;Li et al, 2012;Zhao et al, 2012), US Caucasian for pancreatic cancer (Jiao et al, 2006) as well as Egyptian, Kashmiri, Korean and Japanese for colorectal cancer (Abdel-Rahman et al, 2000;Hong et al, 2005;Yin et al, 2012;Nissar et al, 2013). A recent meta-analysis also suggested that subjects with at least one 399Gln allele elevated the risk of hepatocellular cancer in Asian population (Liu et al, 2013) but other claimed that no direct association of this allele to colorectal cancer (Qin et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Variant Alleles in XRCC1 Arg194Trp and Arg399Gln Polymorphisms Increase Risk of Gastrointestinal Cancer in Sabah, North Borneo

Halim¹,

Chong²,

Goh³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Background: The XRCC1 protein facilitates various DNA repair pathways; single-nucleotide polymorphisms (SNPs) in this gene are associated with a risk of gastrointestinal cancer (GIC) with inconsistent results, but no data have been previously reported for the Sabah, North Borneo, population. We accordingly investigated the XRCC1 Arg194Trp and Arg399Gln SNPs in terms of GIC risk in Sabah. Materials and Methods: We performed genotyping for both SNPs for 250 GIC patients and 572 healthy volunteers using a polymerase chain reactionrestriction fragment length polymorphism approach. We validated heterozygosity and homozygosity for both SNPs using direct sequencing. Results: The presence of a variant 194Trp allele in the Arg194Trp SNP was significantly associated with a higher risk of GIC, especially with gastric and colorectal cancers. We additionally found that the variant 399Gln allele in Arg399Gln SNP was associated with a greater risk of developing gastric cancer. Our combined analysis revealed that inheritance of variant alleles in both SNPs increased the GIC risk in Sabah population. Based on our etiological analysis, we found that subjects ≥50 years and males who carrying the variant 194Trp allele, and Bajau subjects carrying the 399Gln allele had a significantly increased risk of GIC. Conclusions: Our findings suggest that inheritance of variant alleles in XRCC1 Arg194Trp and Arg399Gln SNPs may act as biomarkers for the early detection of GIC, especially for gastric and colorectal cancers in the Sabah population.

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Arg399Gln polymorphism of XRCC1 gene and risk of colorectal cancer in Kashmir: A case control study

Cited by 28 publications

References 24 publications

The Codon 399 Arg/Gln XRCC1 Polymorphism is Associated with Lung Cancer in Indians

The Codon 399 Arg/Gln XRCC1 Polymorphism is Associated with Lung Cancer in Indians

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

Variant Alleles in XRCC1 Arg194Trp and Arg399Gln Polymorphisms Increase Risk of Gastrointestinal Cancer in Sabah, North Borneo

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