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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 8  |  Page : 264-267

X-ray cross-complementing groups 1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility: A meta-analysis based on Chinese Han population


Department of Gastroenterology, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, Zhejiang, China

Date of Web Publication22-Feb-2017

Correspondence Address:
Fang Xu
Department of Gastroenterology, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, Zhejiang
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.200753

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 > Abstract 

Objective: X-ray cross-complementing groups 1 (XRCC1) rs1799782 C>T polymorphisms and colorectal cancer susceptibility were not clear. The purpose of this study was to evaluate the association between XRCC1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility by meta-analysis.
Materials and Methods: Related databases of Medline, CNKI, and Wanfang were systematic searched for the studies related to XRCC1 rs1799782 C>T polymorphisms and colorectal cancer risk in Chinese Han population. The genotype distribution of CC, CT and TT were extracted from each included studies in the colorectal cancer patients and healthy control subjects. The odds ratio (OR) and its 95% confidence interval (95% CI) was used to assess the correlation between genetype and colorectal cancer risk. The publications for this study was evaluated by Begg's funnel plot and Egger's line regression test.
Results: The median frequency of CC, CT, and TT genotype in cancer group were 48%, 41% and 11%; For control group, they were 51%, 40% and 8%; the pooled results showed that OR = 1.32 (95% CI: 1.041–1.67, P < 0.05). The pooled results indicated that XRCC1 rs1799782 C>T polymorphisms was associated with colorectal cancer susceptibility in recessive genetic model OR = 1.32 (95% CI: 1.041–1.67, P < 0.05), dominant genetic model OR = 1.21 (95% CI: 1.00–1.46, P < 0.05) and homozygous genetic model OR = 1.43 (95% CI: 1.07–1.91, P < 0.05). The funnel plot was significant asymmetric at the bottom and the Egger's test also indicated significant publication bias (t = 2.43, P = 0.04) for recessive genetic model. But, no publication bias was found in dominant and homozygous model (P > 0.05).
Conclusion: Chinese Han people with rs1799782 TT/CT genotype of XRCC1 gene may have increased risk of developing colorectal.

Keywords: Colorectal cancer, meta-analysis, polymorphisms, susceptibility, X-ray cross-complementing groups 1 gene


How to cite this article:
Wang L, Qian J, Ying C, Zhuang Y, Shang X, Xu F. X-ray cross-complementing groups 1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility: A meta-analysis based on Chinese Han population. J Can Res Ther 2016;12:264-7

How to cite this URL:
Wang L, Qian J, Ying C, Zhuang Y, Shang X, Xu F. X-ray cross-complementing groups 1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility: A meta-analysis based on Chinese Han population. J Can Res Ther [serial online] 2016 [cited 2017 Mar 26];12:264-7. Available from: http://www.cancerjournal.net/text.asp?2016/12/8/264/200753


 > Introduction Top


Colorectal cancer is one of the most diagnosed malignant tumors of digestive system. It was estimated about seventy colorectal patients dead each year worldwide.[1] And this number was still on the rise. In China, colorectal cancer is the 4th most happed malignant carcinoma inferior to lung cancer, breast cancer, and stomach cancer.[2] Epidemiology study showed the confirmed risk factors for colorectal cancer were colorectal cancer family history, familial hereditary adenoma, obesity, less activity, and chronic enteritis.[3]

X-ray cross-complementing groups 1 (XRCC-1) in humans is encoded by the XRCC1 gene. XRCC1 is involved in DNA repair where it complexes with DNA ligase III.[4] XRCC1 is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. Several studies have reported the association between XRCC-1 rs1799782 C>T polymorphisms and colorectal cancer. However, the results were not consistent.


 > Materials and Methods Top


Publication searching and inclusion

The databases of PubMed/Medline, EMBASE, and CNKI were systematic searched by two reviewers independently to find the potential applicable case–control or cohort publications. The search words were (colorectal cancer or colorectal carcinoma or colon cancer) and (XRCC1) and (polymorphisms or variant). The publication inclusion criteria were: (1) Study type: Case–control or cohort study; (2) patients: The patients included in each study were Chinese Han people diagnosed with colorectal cancer with pathology confirmation; (3) genotyping method: The genotyping method was correct; (4) publication language: The paper was published in English or Chinese.

Data extraction

The following information and data were extracted by two reviewers independently: (1) author of each study; (2) the year of each paper publication; (3) province the study was performed; (4) genotype of CC, CT and TT distribution; (5) genotyping methods; (6) Hardy–Weinberg equilibrium.

Statistical analysis

The statistical analysis was done by STATA/SE 11.0 (Stata Corporation, College Station, TX) software. The statistical heterogeneity was evaluated by Chi-square test. The association between XRCC1 and colorectal cancer susceptibility was demonstrated by odds ratio (OR). The publication bias was evaluated by Begg's funnel plot and Egger's test. Two-tail P < 0.05 was deemed as statistical difference.


 > Results Top


General characteristics of the included articles

After searching the related databases, we finally included 11 case–control studies in our present meta-analysis. Seven of the included studies published in Chinese and other four published in English. The main characters of the included studies were shown in [Table 1].
Table 1: General characteristics of included studies

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Genotype distribution

The median frequency of CC, CT, and TT genotype in case group was 48%, 41%, and 11%; for control group, they were 51%, 40%, and 8%, respectively [Figure 1].
Figure 1: The genotype distribution of CC, CT, and TT for the case and control groups

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Meta-analysis

Recessive genetic model (TT vs. CC + CT)

Being the significant statistical heterogeneity across the included studies (P < 0.05), the data were pooled by random effects model. The pooled results showed that OR = 1.32 (95% confidence interval [CI]: 1.041–1.67, P < 0.05). The pooled results indicated that XRCC1 rs1799782 C>T polymorphisms was associated with colorectal cancer susceptibility in recessive genetic model [Figure 2]. Publication bias was evaluated by Begg's funnel plot and Egger's line regression test. The funnel plot was significant asymmetric at the bottom, and the Egger's test also indicated significant publication bias (t = 2.43, P = 0.04), [Figure 3].
Figure 2: Forest plot of X-ray cross-complementing groups 1 rs1799782 C>T polymorphisms and colorectal cancer for recessive model

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Figure 3: The Begg's funnel plot of recessive genetic model

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Dominant genetic model (TT + CT vs. CC)

With significant statistical heterogeneity across the included studies (P < 0.05), the data were pooled by random effects model for dominant genetic model. The pooled results showed that OR = 1.21 (95% CI: 1.00–1.46, P < 0.05). The pooled results indicated that XRCC1 rs1799782 C>T polymorphisms was associated with colorectal cancer susceptibility in dominant genetic model, [Figure 4]. The funnel plot was significant symmetric at the bottom and the Egger's test did not indicated significant publication bias (t = 0.31, P = 76) [Figure 5].
Figure 4: Forest plot of X-ray cross-complementing groups 1 rs1799782 C>T polymorphisms and colorectal cancer for dominant genetic model

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Figure 5: The Begg's funnel plot of dominant genetic model

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Homozygous genetic model (TT vs. CC)

For homozygous model (TT vs. CC), the statistical heterogeneity was significant for the included 11 studies (P = 0.05). The data were pooled by random effects model. The pooled OR = 1.43 (95% CI: 1.07–1.91, P < 0.05) [Figure 6]. The pooled data indicated that people with TT genotype polymorphisms were susceptible to colorectal cancer in homozygous genetic model. And, funnel plot indicated no publication bias [Figure 7].
Figure 6: Forest plot of X-ray cross-complementing groups 1 rs1799782 C>T polymorphisms and colorectal cancer for homozygous genetic model

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Figure 7: The Begg's funnel plot of homozygous genetic model

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 > Discussion Top


Recently, more and more studies have showed that the cancer gene or tumor suppressor gene single nucleotide polymorphism had affect the cancer development and progression. XRCC1 gene, in human beings, located on human chromosome 19 long arm region (19q13.2-19q13.2). The protein encoded by XRCC1 play a role in interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. Animal experiment showed deficiency in XRCC1, due to being heterozygous for a mutated XRCC1 gene coding for a truncated XRCC1 protein, suppresses tumor growth in mice. In human beings, several studies showed that XRCC1 rs1799782 C>T polymorphisms was associated with the susceptibility. Li and et al.[4] have discussed the polymorphisms in genes of APE1, PARP1, and XRCC for the risk and prognosis of colorectal cancer in a northeast Chinese population. In their study, the author included 451 colorectal cancer patients and 631 healthy controls. They found XRCC1 194 dominant model (OR = 1.45, 95% CI 1.12–1.88) were associated with increased CRC risk. But Jin et al.[5] had investigated correlations of single nucleotide polymorphisms of DNA repair gene XRCCl to risk of colorectal cancer. They recruited 207 colorectal patients and 621 healthy controls. They found no significant correlation between XRCC1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility. Therefore, the results of Li and Jin were contrary.

We have searched the databases of PubMed and CNKI to find all the open published studies related to XRCC1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility. And the data were pooled by meta-analysis. The pooled results showed XRCC1 rs1799782 C>T polymorphisms was associated with colorectal cancer susceptibility in recessive genetic model OR = 1.32 (95% CI: 1.041–1.67, P < 0.05), dominant genetic model OR = 1.21 (95% CI: 1.00–1.46, P < 0.05) and homozygous genetic model OR = 1.43 (95% CI: 1.07–1.91, P < 0.05). So, Chinese Han people with rs1799782 TT/CT genotype of XRCC1 gene may have increased risk of developing colorectal cancer.

Limitations for this meta-analysis: (1) In this meta-analysis, the publication bias for homozygous genetic model was significant. (2) Significant statistical heterogeneity was found in recessive genetic model, dominant genetic model, and homozygous genetic model. [14]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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Benson AB 3rd. Epidemiology, disease progression, and economic burden of colorectal cancer. J Manag Care Pharm 2007;13 6 Suppl C: S5-18.  Back to cited text no. 1
    
2.
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Li Y, Li S, Wu Z, Hu F, Zhu L, Zhao X, et al. Polymorphisms in genes of APE1, PARP1, and XRCC1: Risk and prognosis of colorectal cancer in a Northeast Chinese population. Med Oncol 2013;30:505.  Back to cited text no. 4
    
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Jin MJ, Chen K, Zhang Y, Zhang W, Liu B, Zhang YJ. Correlations of single nucleotide polymorphisms of DNA repair gene XRCCl to risk of colorectal cancer. Chin J Cancer 2007;26:136-42.  Back to cited text no. 5
    
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Huang S, Yi B, Yang XH, Rui R, Miao XP. Polymorphisms of DNA repair gene XRCC1 and genetic susceptibility to colorectal cancer. Chin J Exp Surg 2010;27:1057-9.  Back to cited text no. 7
    
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Yang XD, Xing CG, Zhao K, Gong W, Wu YY, Zhong FY, et al. Correlation of single nucleotide polymorphisms of X-ray repair cross complementing group 1 gene to hereditary susceptibility of colorectal cancer. Chin J Gastrointest Surg 2013;16:1195-8.  Back to cited text no. 9
    
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Gao CM, Ding JH, Li SP, Liu YT, Cao HX, Wu JZ, et al. Polymorphisms in XRCC1 gene, alcohol drinking, and risk of colorectal cancer: A case–control study in Jiangsu Province of China. Asian Pac J Cancer Prev 2014;14:6613-8.  Back to cited text no. 10
    
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Xu JC, Ren WC, Bi YH. Study on the relationship between genetic polymorphism of DNA repair gene-XRCC1 and the susceptibility to colorectal cancer. Chin J Coal Ind Med 2014;17:558-61.  Back to cited text no. 11
    
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Shen H, Zhao DY, Zhang Y. XRCC1 Arg194Trp polymorphisms and colorectal cancer susceptibility. Chin J Clin Ca 2014;21:476-8.  Back to cited text no. 12
    
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Huang Y, Li X, He J, Chen L, Huang H, Liang M, et al. Genetic polymorphisms in XRCC1 genes and colorectal cancer susceptibility. World J Surg Oncol 2015;13:244.  Back to cited text no. 13
    
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Dai Q, Luo H, Li XP, Huang J, Zhou TJ, Yang ZH. XRCC1 and ERCC1 polymorphisms are related to susceptibility and survival of colorectal cancer in the Chinese population. Mutagenesis 2015;30:441-9.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

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