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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 12  |  Page : 1178-1182

Association of X-ray cross-complementing group 3 Thr241Met gene polymorphism with osteosarcoma risk and its development and prognosis


1 Department of TCM Orthopedics, The First Affiliated Hospital of Xiamen University, Xiamen (Amoy) 361000, China
2 Department of TCM Orthopedics, No. 60 Center Hospital of People's Liberation Army, Dali 671000, China
3 Department of Surgery, The Affiliated Hospital of Putian University, Putian 351100, China

Date of Web Publication11-Dec-2018

Correspondence Address:
Zhiyong Dong
No. 999 Dongzhen Load, Licheng District, Putian City, Fujian Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.199435

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 > Abstract 


Aim of Study: The relationship between X-ray cross-complementing group 3 (XRCC3) Thr241Met gene polymorphism and osteosarcoma risk and its development and prognosis is still debated. This meta-analysis was performed to assess these associations.
Materials and Methods: The association studies were identified from PubMed, and eligible reports were included and calculated using meta-analysis method.
Results: Interestingly, all the included studies were from Asian population. The meta-analysis indicated that XRCC3 Thr241Met gene polymorphism was associated with osteosarcoma risk (T allele: Odds ratio [OR] =1.57, 95% confidence interval [CI]: 1.25–1.98, P = 0.0001; TT genotype: OR = 2.23, 95% CI: 1.40-3.57, P = 0.0008; CC genotype: OR = 0.69, 95% CI: 0.54–0.87, P = 0.002). However, XRCC3 Thr241Met CC genotype was not associated with Enneking stage, tumor location, and tumor metastasis.
Conclusion: XRCC3 Thr241Met gene polymorphism was associated with osteosarcoma risk, but XRCC3 Thr241Met CC genotype was not associated with Enneking stage, tumor location, and tumor metastasis.

Keywords: Gene polymorphism, meta-analysis, osteosarcoma, Thr241Met, X-ray cross-complementing group 3


How to cite this article:
Wang Y, Wang G, Dong Z. Association of X-ray cross-complementing group 3 Thr241Met gene polymorphism with osteosarcoma risk and its development and prognosis. J Can Res Ther 2018;14, Suppl S5:1178-82

How to cite this URL:
Wang Y, Wang G, Dong Z. Association of X-ray cross-complementing group 3 Thr241Met gene polymorphism with osteosarcoma risk and its development and prognosis. J Can Res Ther [serial online] 2018 [cited 2019 Sep 20];14:1178-82. Available from: http://www.cancerjournal.net/text.asp?2018/14/12/1178/199435




 > Introduction Top


Osteosarcoma is the most common primary malignant bone tumor in children and adolescents.[1],[2] Osteosarcomas are aggressive and have a high incidence of recurrence and metastasis, and effective therapy has not yet been developed. The different etiology might contribute to the bimodal incidence distribution, and the first peak among adolescents overlaps with the time of rapid adolescent bone growth and might be associated with rapid bone proliferation.[3] On the other hand, among adults, osteosarcoma may be associated more with exposure to environmental factors and can also represent a secondary malignancy. To develop a good indicator for the early diagnosis of osteosarcomas and to find a good indicator to predict the osteosarcomas development, prognosis is urgently needed.

X-ray cross-complementing group 3 (XRCC3) gene encodes a protein that can play an important role in the homologous recombination repair of DNA double-strand break.[4] Increasing attention has been drawn to the association of XRCC3 Thr241Met gene polymorphism with various types of human cancers.[4] XRCC3 Thr241Met (rs861539) gene polymorphism, with a Thr-to-Met amino acid conversion, is caused by a C-to-T nucleotide change at codon 241.[4] Three genotypes have been identified for this gene polymorphism, namely, wild-type (CC), heterozygote (CT), and homozygote (TT).[5] Current evidence shows that XRCC3 Thr241Met gene polymorphism can take part in the pathogenesis of osteosarcomas. This meta-analysis was performed to assess the association between XRCC3 Thr241Met gene polymorphism and osteosarcomas risk and its development and prognosis.


 > Materials and Methods Top


Search strategy

The search was conducted in the databases of PubMed on June 1, 2016, and the relevant investigations were included. The retrieval strategy of “XRCC3 AND polymorphism AND (osteosarcoma OR bone tumor OR bone cancer OR bone carcinoma)” was entered into the PubMed database.

Inclusion and exclusion criteria

Inclusion criteria

(1) The outcome must be osteosarcoma; (2) the study included two comparison groups (osteosarcoma group vs. control group); (3) report should give the data of XRCC3 genotype distribution.

Exclusion criteria

(1) Case reports, editorials, and review articles; (2) preliminary result not on XRCC3 gene polymorphism or osteosarcoma; (4) investigating the role XRCC3 gene expression to osteosarcoma.

Data extraction

The following information from each recruited investigation was extracted by two investigators independently: first author's surname, year of publication, ethnicity, control source of the control group, and the number of cases and controls for XRCC3 genotypes. Frequencies of allele of XRCC3 were calculated for case and control groups.

Statistical Analysis

Cochrane Review Manager Version 5 (Cochrane Library, UK) was used in this meta-analysis to count the extracted data from each report. The pooled statistic was counted using the fixed effects model. However, a random effects model was conducted when the P value of heterogeneity test was <0.1. Results were expressed using odds ratios (OR) for dichotomous data. 95% confidence intervals (CI) were also calculated. P < 0.05 was required for the pooled OR to be statistically significant, and I2 was used to test the heterogeneity among the included studies. Sensitivity analysis was also performed according to the source of the controls (population-based vs. hospital-based).


 > Results Top


Association of X-ray cross-complementing group 3 Thr241Met gene polymorphism with osteosarcoma risk

Three studies[6],[7],[8] for the relationship between XRCC3 Thr241Met gene polymorphism and osteosarcoma risk were included in this meta-analysis. Interestingly, all the included studies were from Asian population [Table 1]. We found that XRCC3 Thr241Met gene polymorphism was associated with osteosarcoma risk (T allele: OR = 1.57, 95% CI: 1.25–1.98, P = 0.0001; TT genotype: OR = 2.23, 95% CI: 1.40–3.57, P = 0.0008; CC genotype: OR = 0.69, 95% CI: 0.54–0.87, P = 0.002; [Figure 1] and [Table 2]).
Table 1: General characteristics of the included studies in this meta-analysis for XRCC3 Thr241Met gene polymorphism with osteosarcoma risk and its development, prognosis

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Figure 1: Association between XRCC3 Thr241Met gene polymorphism and osteosarcoma risk

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Table 2: Meta-analysis of the association of XRCC3 Thr241Met and ERCC3 gene polymorphism with osteosarcoma risk and its development, prognosis

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Sensitivity analysis was also performed according to the source of the controls (population-based vs. hospital-based). The results from this sensitivity analysis of population-based were similar with those from nonsensitivity analysis, and XRCC3 Thr241Met gene polymorphism was associated with osteosarcoma risk [Table 2]. Furthermore, the results from this sensitivity analysis of hospital-based indicated that T allele and TT genotype were associated with osteosarcoma risk [Table 2]. However, CC genotype was not associated with osteosarcoma risk [Table 2].

Association of X-ray cross-complementing group 3 Thr241Met gene polymorphism with Enneking stage

Two studies[6],[8] for the relationship between XRCC3 Thr241Met gene polymorphism and Enneking stage were included in this meta-analysis; we found that XRCC3 Thr241Met CC genotype was not associated with Enneking stage (OR = 0.95, 95% CI: 0.58–1.53, P = 0.82; [Table 2]).

Sensitivity analysis was also performed according to the source of the controls (population based vs. hospital based). The results from this sensitivity analysis of population-based were similar with those from nonsensitivity analysis, and the results from this sensitivity analysis of hospital based were also similar with those from nonsensitivity analysis. XRCC3 Thr241Met CC genotype was not associated with Enneking stage [Table 2].

Association of X-ray cross-complementing group 3 Thr241Met gene polymorphism with tumor location

Two studies[6],[8] for the relationship between XRCC3 Thr241Met gene polymorphism and tumor location were included in this meta-analysis; we found that XRCC3 Thr241Met CC genotype was not associated with tumor location (OR = 1.15, 95% CI: 0.69–1.91, P = 0.59; [Table 2]).

Sensitivity analysis was also performed according to the source of the controls (population based vs. hospital based). The results from this sensitivity analysis of population based were similar with those from nonsensitivity analysis, and the results from this sensitivity analysis of hospital based were also similar with those from nonsensitivity analysis. XRCC3 Thr241Met CC genotype was not associated with tumor location [Table 2].

Association of X-ray cross-complementing group 3 Thr241Met gene polymorphism with tumor metastasis

Two studies[6],[8] for the relationship between XRCC3 Thr241Met gene polymorphism and tumor metastasis were included in this meta-analysis; we found that XRCC3 Thr241Met CC genotype was not associated with tumor metastasis (OR = 0.92, 95% CI: 0.57–1.48, P = 0.73; [Table 2]).

Sensitivity analysis was also performed according to the source of the controls (population based vs. hospital based). The results from this sensitivity analysis of population based were similar with those from nonsensitivity analysis, and the results from this sensitivity analysis of hospital-based were also similar with those from nonsensitivity analysis. XRCC3 Thr241Met CC genotype was not associated with tumor metastasis [Table 2].


 > Discussion Top


This meta-analysis was the first meta-analysis to detect the relationship between XRCC3 Thr241Met gene polymorphism and osteosarcomas risk and its development and prognosis. Interestingly, all the included reports were from Asians. We found that XRCC3 Thr241Met gene polymorphism was associated with osteosarcoma risk. Sensitivity analysis was also performed according to the source of the controls (population based vs. hospital based). The results from this sensitivity analysis of population based were similar with those from nonsensitivity analysis, and XRCC3 Thr241Met gene polymorphism was associated with osteosarcoma risk.

However, when we detect the relationship between XRCC3 Thr241Met gene polymorphism and osteosarcomas development and prognosis, we found that XRCC3 Thr241Met CC genotype was not associated with Enneking stage, tumor location, and tumor metastasis. However, the number of included studies was small, and more well-designed studies should be performed in the future.

There were reports studied the association of XRCC3 Thr241Met gene polymorphism and response to chemotherapy, event-free and overall survival in osteosarcoma patients. Ji and He[9] investigated the DNA-repair gene polymorphisms and response to chemotherapy and overall survival of osteosarcoma and reported that XRCC3 Thr241Met gene polymorphism was not associated with the response to cisplatin-based chemotherapy in osteosarcoma patients. Goricar et al.[3] studied the genetic variability of DNA-repair mechanisms influenced treatment outcome in osteosarcoma and reported that XRCC3 Thr241Met gene polymorphism was not associated with response to chemotherapy, event-free and overall survival in osteosarcoma patients.

There were some meta-analyses to test the relationship between XRCC3 Thr241Met gene polymorphism and other diseases. Zeng et al.[10] included a total of eight case–control studies in the meta-analysis to assess the influence of XRCC3 rs861539 polymorphism on cutaneous melanoma susceptibility and reported that the XRCC3 rs861539 polymorphism was not a risk factor for cutaneous melanoma susceptibility. Li et al.[11] performed a meta-analysis to detect the relationship between XRCC3 Thr241Met gene polymorphisms and laryngeal cancer risk, and the results indicated that XRCC3 Thr241Met gene polymorphisms was not associated with laryngeal cancer risk. However, Chai et al.[12] performed a meta-analysis of association between XRCC3 Thr241Met polymorphism and the risk of breast cancer and concluded that XRCC3 Thr241Met polymorphism might be associated with breast cancer risk, especially in Asian populations and in patients without family history of breast cancer. In our meta-analysis, we found that XRCC3 Thr241Met gene polymorphism was associated with osteosarcoma risk. In different diseases, the association results might be different.


 > Conclusion Top


XRCC3 Thr241Met gene polymorphism was associated with osteosarcoma risk, but XRCC3 Thr241Met CC genotype was not associated with Enneking stage, tumor location, and tumor metastasis. However, more association investigations are required to confirm these associations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
De S, Ghosh S, Mondal D, Sur PK. Osteosarcoma of the mandible – Second cancer in a case of Hodgkin's lymphoma post-chemotherapy. J Cancer Res Ther 2010;6:336-8.  Back to cited text no. 1
    
2.
Vijayan S, Naik MA, Hameed SA, Rao SK. Giant cell rich osteosarcoma of the cuneiforms. J Cancer Res Ther 2015;11:989-92.  Back to cited text no. 2
    
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Goricar K, Kovac V, Jazbec J, Zakotnik B, Lamovec J, Dolžan V. Genetic variability of DNA repair mechanisms and glutathione-S-transferase genes influences treatment outcome in osteosarcoma. Cancer Epidemiol 2015;39:182-8.  Back to cited text no. 3
    
4.
Lu W, Wu G, Zhang B. Association between X-ray cross-complementing group 3 (XRCC3) Thr241Met polymorphism and risk of thyroid cancer: A meta-analysis. Med Sci Monit 2015;21:3978-85.  Back to cited text no. 4
    
5.
Ji RB, Qian YS, Hu AR, Hu YR. DNA repair gene XRCC3 T241M polymorphism and susceptibility to hepatocellular carcinoma in a Chinese population: A meta-analysis. Genet Mol Res 2015;14:15988-96.  Back to cited text no. 5
    
6.
Guo J, Lv HC, Shi RH, Liu WL. Association between XRCC3 Thr241Met polymorphism and risk of osteosarcoma in a Chinese population. Genet Mol Res 2015;14:16484-90.  Back to cited text no. 6
    
7.
Jin G, Wang M, Chen W, Shi W, Yin J, Gang W. Single nucleotide polymorphisms of nucleotide excision repair and homologous recombination repair pathways and their role in the risk of osteosarcoma. Pak J Med Sci 2015;31:269-73.  Back to cited text no. 7
    
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Yang L, An Y, Wang G, Lu T, Yang S. Association between XRCC3 Thr241Met polymorphism and risk of osteosarcoma in a Chinese population. Int J Clin Exp Pathol 2015;8:11670-4.  Back to cited text no. 8
    
9.
Ji WP, He NB. Investigation on the DNA repaired gene polymorphisms and response to chemotherapy and overall survival of osteosarcoma. Int J Clin Exp Pathol 2015;8:894-9.  Back to cited text no. 9
    
10.
Zeng Y, Ma F, Gao W, Wang Y, Liu C. Quantitative assessment of the influence of X-ray repair cross-complementing group 3 rs861539 polymorphism and cutaneous melanoma susceptibility. Arch Dermatol Res 2016;308:173-81.  Back to cited text no. 10
    
11.
Li F, Wang J, Chen M. Single nucleotide polymorphisms in DNA repair genes and the risk of laryngeal cancer: A meta-analysis. Biomed Pharmacother 2016;78:92-100.  Back to cited text no. 11
    
12.
Chai F, Liang Y, Chen L, Zhang F, Jiang J. Association between XRCC3 Thr241Met polymorphism and risk of breast cancer: Meta-analysis of 23 case-control studies. Med Sci Monit 2015;21:3231-40.  Back to cited text no. 12
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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