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Genetic polymorphisms in XRCC1 genes and colorectal cancer susceptibility.

Huang Y, Li X, He J, Chen L, Huang H, Liang M, Zhu Q, Huang Y, Wang L, Pan C, Xia T - World J Surg Oncol (2015)

Bottom Line: Taking smoking and drinking habits into consideration, we found that subjects with heavy smoking history and XRCC1 194Arg allele had the significantly increased risk for CRC (OR=2.91, 95% CI 1.35-6.24).In smoking population, 194Arg (P=0.491) and 399Gln (P=0.912) had not significantly increased risk for CRC, so did 399Gln (P=0.812) in smoking population.But XRCC1 399Gln allele or 194Arg allele were not independent risk factors for CRC in smoking or drinking population.

View Article: PubMed Central - PubMed

Affiliation: The First Affiliated Hospital of Nanjing Medical University, 68 Changle Road, 210006, Nanjing, People's Republic of China. huangyi0020@126.com.

ABSTRACT

Background: The objective of this study is to investigate the association among the polymorphisms of XRCC1 gene, smoking, drinking, family history of tumors, and the risk of colorectal cancer (CRC) in the population of Han nationality in Jiangsu Province, China.

Methods: A case-control study of 320 patients with CRC and 350 cancer-free subjects as a control group was conducted. The three polymorphic sites, codons 194, 280, and 399, of XRCC1 genes were analyzed by PCR-RFLP.

Results: We find that heavy smoking (>500 cigarettes per year) significantly increased the susceptibility of CRC (OR=1.89, 95% confidence interval (CI) 1.27-2.84) after stratification by total smoking amount. There was also significant difference between cases and controls when family history of tumors (OR=2.96, 95% CI 1.76-4.99) was considered. Comparing with individuals carrying XRCC1 399Arg/Arg genotype, the subjects with 399Arg/Gln (OR=1.46, 95% CI 1.06-2.01) or 399Gln/Gln genotype (OR=1.93, 95% CI 1.05-3.54) had a significantly increased risk for CRC. Taking smoking and drinking habits into consideration, we found that subjects with heavy smoking history and XRCC1 194Arg allele had the significantly increased risk for CRC (OR=2.91, 95% CI 1.35-6.24). Individuals, who carry 399Gln allele and have a heavy smoking (OR=2.72, 95% CI 1.52-4.89) or drinking habit (OR=1.98, 95% CI 1.06-3.67), also have higher risk. In smoking population, 194Arg (P=0.491) and 399Gln (P=0.912) had not significantly increased risk for CRC, so did 399Gln (P=0.812) in smoking population.

Conclusions: Individuals carrying XRCC1 399Gln allele with a smoking or drinking habit were in increased risk, and heavy-smoking subjects with 194Arg allele also have higher risk for CRC in the Han nationality population of Jiangsu Province, which also showed a positive correlation with exposure dose of tobacco. But XRCC1 399Gln allele or 194Arg allele were not independent risk factors for CRC in smoking or drinking population.

No MeSH data available.


Related in: MedlinePlus

Detection of the genotypes of XRCC1 Arg194Trp, Arg280His, and Arg399Gln sites. a The genotypes of XRCC1 Arg194Trp sites. b The genotypes of XRCC1 Arg280His sites. c The genotypes of XRCC1 Arg399Gln sites; M: DNA marker ladder; A/A: Arg/Arg; A/T: Arg/Trp; T/T: Trp/Trp; A/H: Arg/His; H/H: His/His; A/G: Arg/Gln; G/G: Gln/Gln; A/T, A/H, A/G: heterozygous genotype
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Fig1: Detection of the genotypes of XRCC1 Arg194Trp, Arg280His, and Arg399Gln sites. a The genotypes of XRCC1 Arg194Trp sites. b The genotypes of XRCC1 Arg280His sites. c The genotypes of XRCC1 Arg399Gln sites; M: DNA marker ladder; A/A: Arg/Arg; A/T: Arg/Trp; T/T: Trp/Trp; A/H: Arg/His; H/H: His/His; A/G: Arg/Gln; G/G: Gln/Gln; A/T, A/H, A/G: heterozygous genotype

Mentions: Successfully amplified samples were digested with Pvu II, Rsa I, and Msp I [4, 8, 9, 13]. The volume of enzyme reaction system was 12 μL including 1 μL of 10× buffer, 5 U of restriction endonucleases, 0.1 μL bovine serum albumin, and 10 μL of PCR products. After the reaction system of enzymatic digestion was kept in 37 °C water for 3–6 h, the digested products were allowed to electrophorese on 3 % agarose gels in order to analyze the genotypes of samples (Fig. 1).The XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The primer sequences were selected by referring to published papers and Primer3 software [4, 8, 9, 13]. The total volume of PCR reaction system was 30 μL, containing 3.0 μL of 10 PCR buffer, 2.5 μL of 25 mmol/L MgCl, 0.5 μL of 10 mM/L dNTP, 0.3 μL of 25 μM/L each primer, 0.25 μL of 5 U/mL Taq DNA polymerase, and 100 ng of genomic DNA. The PCR amplification consisted of an initial 5-min incubation at 94 °C, followed by 35 cycles of denaturing at 94 °C for 30 s, various annealing conditions [4, 8, 9, 13], and an extension at 72 °C for 50 s. The reaction was terminated after a final extension of 10 min at 72 °C.Fig. 1


Genetic polymorphisms in XRCC1 genes and colorectal cancer susceptibility.

Huang Y, Li X, He J, Chen L, Huang H, Liang M, Zhu Q, Huang Y, Wang L, Pan C, Xia T - World J Surg Oncol (2015)

Detection of the genotypes of XRCC1 Arg194Trp, Arg280His, and Arg399Gln sites. a The genotypes of XRCC1 Arg194Trp sites. b The genotypes of XRCC1 Arg280His sites. c The genotypes of XRCC1 Arg399Gln sites; M: DNA marker ladder; A/A: Arg/Arg; A/T: Arg/Trp; T/T: Trp/Trp; A/H: Arg/His; H/H: His/His; A/G: Arg/Gln; G/G: Gln/Gln; A/T, A/H, A/G: heterozygous genotype
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4536607&req=5

Fig1: Detection of the genotypes of XRCC1 Arg194Trp, Arg280His, and Arg399Gln sites. a The genotypes of XRCC1 Arg194Trp sites. b The genotypes of XRCC1 Arg280His sites. c The genotypes of XRCC1 Arg399Gln sites; M: DNA marker ladder; A/A: Arg/Arg; A/T: Arg/Trp; T/T: Trp/Trp; A/H: Arg/His; H/H: His/His; A/G: Arg/Gln; G/G: Gln/Gln; A/T, A/H, A/G: heterozygous genotype
Mentions: Successfully amplified samples were digested with Pvu II, Rsa I, and Msp I [4, 8, 9, 13]. The volume of enzyme reaction system was 12 μL including 1 μL of 10× buffer, 5 U of restriction endonucleases, 0.1 μL bovine serum albumin, and 10 μL of PCR products. After the reaction system of enzymatic digestion was kept in 37 °C water for 3–6 h, the digested products were allowed to electrophorese on 3 % agarose gels in order to analyze the genotypes of samples (Fig. 1).The XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The primer sequences were selected by referring to published papers and Primer3 software [4, 8, 9, 13]. The total volume of PCR reaction system was 30 μL, containing 3.0 μL of 10 PCR buffer, 2.5 μL of 25 mmol/L MgCl, 0.5 μL of 10 mM/L dNTP, 0.3 μL of 25 μM/L each primer, 0.25 μL of 5 U/mL Taq DNA polymerase, and 100 ng of genomic DNA. The PCR amplification consisted of an initial 5-min incubation at 94 °C, followed by 35 cycles of denaturing at 94 °C for 30 s, various annealing conditions [4, 8, 9, 13], and an extension at 72 °C for 50 s. The reaction was terminated after a final extension of 10 min at 72 °C.Fig. 1

Bottom Line: Taking smoking and drinking habits into consideration, we found that subjects with heavy smoking history and XRCC1 194Arg allele had the significantly increased risk for CRC (OR=2.91, 95% CI 1.35-6.24).In smoking population, 194Arg (P=0.491) and 399Gln (P=0.912) had not significantly increased risk for CRC, so did 399Gln (P=0.812) in smoking population.But XRCC1 399Gln allele or 194Arg allele were not independent risk factors for CRC in smoking or drinking population.

View Article: PubMed Central - PubMed

Affiliation: The First Affiliated Hospital of Nanjing Medical University, 68 Changle Road, 210006, Nanjing, People's Republic of China. huangyi0020@126.com.

ABSTRACT

Background: The objective of this study is to investigate the association among the polymorphisms of XRCC1 gene, smoking, drinking, family history of tumors, and the risk of colorectal cancer (CRC) in the population of Han nationality in Jiangsu Province, China.

Methods: A case-control study of 320 patients with CRC and 350 cancer-free subjects as a control group was conducted. The three polymorphic sites, codons 194, 280, and 399, of XRCC1 genes were analyzed by PCR-RFLP.

Results: We find that heavy smoking (>500 cigarettes per year) significantly increased the susceptibility of CRC (OR=1.89, 95% confidence interval (CI) 1.27-2.84) after stratification by total smoking amount. There was also significant difference between cases and controls when family history of tumors (OR=2.96, 95% CI 1.76-4.99) was considered. Comparing with individuals carrying XRCC1 399Arg/Arg genotype, the subjects with 399Arg/Gln (OR=1.46, 95% CI 1.06-2.01) or 399Gln/Gln genotype (OR=1.93, 95% CI 1.05-3.54) had a significantly increased risk for CRC. Taking smoking and drinking habits into consideration, we found that subjects with heavy smoking history and XRCC1 194Arg allele had the significantly increased risk for CRC (OR=2.91, 95% CI 1.35-6.24). Individuals, who carry 399Gln allele and have a heavy smoking (OR=2.72, 95% CI 1.52-4.89) or drinking habit (OR=1.98, 95% CI 1.06-3.67), also have higher risk. In smoking population, 194Arg (P=0.491) and 399Gln (P=0.912) had not significantly increased risk for CRC, so did 399Gln (P=0.812) in smoking population.

Conclusions: Individuals carrying XRCC1 399Gln allele with a smoking or drinking habit were in increased risk, and heavy-smoking subjects with 194Arg allele also have higher risk for CRC in the Han nationality population of Jiangsu Province, which also showed a positive correlation with exposure dose of tobacco. But XRCC1 399Gln allele or 194Arg allele were not independent risk factors for CRC in smoking or drinking population.

No MeSH data available.


Related in: MedlinePlus