Dear Editor
We read with great interest the recent article by Namazi and colleagues, “association between the XRCC3 Thr241Met polymorphism and risk of colorectal cancer: a meta-analysis of 5,193 cases and 6,645 controls”(Namazi et al., 2015). There are some important negative points decrease the reliability of the article.
Firstly, some contradictory findings exist in this meta-analysis. The author found a significant association between the XRCC3 Thr241Met polymorphism and colorectal cancer under the overall dominant and heterozygous model in Caucasian descent. Our review demonstrated inconsistent results in texture (CC+CT vs. TT: OR=0.575, 95%CI=0.498-1.665, P<0.001, Pheterogeneity=0.00, I2=83%) and diagram of overall dominant model (CC+CT vs. TT: OR=0.904, 95%CI=0.796-1.027, P=0.120). On the other hand, in a stratified analysis by ethnicity, the P value of heterozygous model in Caucasian descent is more than 0.05 (CT vs. TT: OR=0.929, 95%CI=0.806-1.070, P=0.308, Pheterogeneity=0.002, I2=57%). Therefore, it seems to exist no significant association between the XRCC3 Thr241Met polymorphism and colorectal cancer under mentioned genetic models. Moreover, the author reported that the dominant and allelic genetic models of the XRCC3 Thr241Met polymorphism were significantly correlated with increasing risk of CRC in Asian population (Dominant model: CC+CT vs. TT: OR=0.609, 95%CI=0.411-0.902, P=0.013, Pheterogeneity=0.54, I2=0.00%; Allelic model: C vs. T: OR=0.708, 95%CI=0.605-0.829, P=0.000, Pheterogeneity=0.000, I2=92%). Conversely, the OR of dominant and allelic models in Asian descent represent decreasing CRC risk.
Secondly, Namazi et al. mentioned to the extracted genotyping method, the source and genotype distribution of control groups from all included studies and they acclaimed that the allele frequencies among populations of these studies conformed to Hardy-Weinberg equilibrium (HWE). However, the reviewing of the original studies showed contrary to this entry. The allele frequencies among populations of six articles (Krupa and Blasiak, 2004; Jin et al., 2005; Canbay et al., 2011; Krupa et al., 2011; Zhao et al., 2012; Nissar et al., 2014) demonstrated the deviation from HWE (Table 1) and there is no data about the genotyping method and source of the control groups. Furthermore, the author has been mentioned analysis of data was performed by Comprehensive Meta-Analysis software (version 5), while the latest released version of this software is 3.
Table 1.
The Included Studies That Deviated from HWE
| Genotype distribution in controls | |||||||
|---|---|---|---|---|---|---|---|
| First author | Country | Ethnicity | CC | CT | TT | P HWE | Deviated from HWE |
| Nissar et al. 2014 | Kashmir | Asian | 118 | 22 | 10 | <0.001 | Yes |
| Zhao et al. 2012 | China | Asian | 846 | 81 | 43 | <0.001 | Yes |
| Krupa et al. 2011 | Poland | Caucasian | 50 | 47 | 3 | 0.039 | Yes |
| Canbay et al. 2011 | Turkey | Caucasian | 74 | 146 | 27 | <0.001 | Yes |
| Jin et al. 2005 | China | Asian | 268 | 11 | 1 | 0.025 | Yes |
| Krupa and Blasiak et al. 2004 | Poland | Caucasian | 11 | 81 | 8 | <0.001 | Yes |
HWE, Hardy-Weinberg Equilibrium
According to the mentioned points, the results of this meta-analysis study may be not reliable, and the re-evaluating of the relevant studies of the association between XRCC3 Thr241Met polymorphism and the risk of colorectal cancer requires a closer look.
References
- Canbay E, Cakmakoglu B, Zeybek U, et al. Association of APE1 and hOGG1 polymorphisms with colorectal cancer risk in a Turkish population. Curr Med Res Opin. 2011;27:1295–302. doi: 10.1185/03007995.2011.573544. [DOI] [PubMed] [Google Scholar]
- Jin MJ, Chen K, Song L, et al. The association of the DNA repair gene XRCC3 Thr241Met polymorphism with susceptibility to colorectal cancer in a Chinese population. Cancer Genet Cytogenet. 2005;163:38–43. doi: 10.1016/j.cancergencyto.2005.05.001. [DOI] [PubMed] [Google Scholar]
- Krupa R, Blasiak J. An association of polymorphism of DNA repair genes XRCC1 and XRCC3 with colorectal cancer. J Exp Clin Cancer Res. 2004;23:285–94. [PubMed] [Google Scholar]
- Krupa R, Sliwinski T, Wisniewska-Jarosinska M, et al. Polymorphisms in RAD51, XRCC2 and XRCC3 genes of the homologous recombination repair in colorectal cancer- a case control study. Mol Biol Rep. 2011;38:2849–54. doi: 10.1007/s11033-010-0430-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Namazi A, Abedinzadeh M, Nourbaksh P, et al. Association between the XRCC3 Thr241Met polymorphism and risk of colorectal cancer: a meta analysis of 5,193 cases and 6,645 controls. Asian Pac J Cancer Prev. 2015;16:2263–8. doi: 10.7314/apjcp.2015.16.6.2263. [DOI] [PubMed] [Google Scholar]
- Nissar S, Sameer AS, Lone TA, et al. XRCC3 Thr241Met gene polymorphism and risk of colorectal cancer in Kashmir: a case control study. Asian Pac J Cancer Prev. 2014;15:9621–5. doi: 10.7314/apjcp.2014.15.22.9621. [DOI] [PubMed] [Google Scholar]
- Zhao Y, Deng X, Wang Z, et al. Genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 and risk of colorectal cancer in Chinese population. Asian Pac J Cancer Prev. 2012;13:665–9. doi: 10.7314/apjcp.2012.13.2.665. [DOI] [PubMed] [Google Scholar]