Document Type : Original Article

Authors

1 Department of Biochemistry, Neyshabur Medical Sciences Branch, Islamic Azad University, Neyshabur, Iran

2 Radiation Oncology Department, Reza Radiotherapy Oncology Center, Mashhad, Iran

Abstract

Background: The objective of this study was to investigate the effect of several XPA and XPC polymorphisms on the risk of colorectal cancer (CRC) in northeastern Iran.
Method: 180 CRC patients and 160 healthy subjects participated in this case-control study. We determined the genotypes by RFLP-PCR and PIRA-PCR, and analyzed the results using logistic regression and χ2-test.
Results: Our findings showed that only BMI could affect the risk of cancer among the studied demographic factors. Three of the four polymorphisms studied, namely XPA A23G, XPC rs2228000 C > T and XPC rs2228001 A > C, did not correlate with CRC (P-values > 0.05); however, the polymorphism of XPC poly AT (PAT) increased the risk of CRC (P= 0.024). The XPC rs2228000 C> T polymorphism increased the CRC risk only in patients aged 50 or more. The risk of CRC in heterozygote individuals (XPC PAT D/I) was higher than that of homozygous individuals (XPC PAT D/D); also, at least one PAT I variant allele increased the likelihood of CRC (for PAT D/I OR =2.168; 95% CI = 1.809-4.319: and for PAT D/I and PAT I/I OR = 1.810; 95% CI = 1.165-2.813). The XPC haplotypes were similar between the cases and controls, and P-values were >0.05.
Conclusion: In the whole population, XPC PAT polymorphism, overweightness, and XPC rs2228000 C>T polymorphism in elderly people are related to CRC. Therefore, they can probably be considered as markers of CRC in Iran.

Keywords

How to cite this article:

Mehrzad J, Dayyani M, Erfanian-Khorasani M. The relationship of XPA and XPC gene polymorphisms with the risk of colorectal cancer in Iran. Middle East J Cancer. 2020;11(4): 445-53. doi: 10. 30476/mejc.2020.81864.1045.

 
1. Haggar FA, Robin P, Boushey M. Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors. Clin Colon AND Rectal Surg. 2009; 22(4): 191-197.
 
2. Basu AK. DNA Damage, Mutagenesis and Cancer. Int J Mol Sci. 2018; 19(4), 970.
 
3. Sugitani N, Shell SM, Soss SE, Chazin WJ. Redefining the DNA-binding domain of human XPA. J Am Chem Soc, 2014; 136(31): 10830-3.
 
4. Ziani SNagy ZAlekseev SSoutoglou EEgly JM, Coin F. Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin. J Cell Biol, 2014; 206: 589–598.
 
5. Park CH, Mu D, Reardon JT, Sancar A. The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor. J Biol Chem, 1995; 270: 4896–4902.
 
6. Camenisch U, Nageli H. XPA gene, its product and biological roles. Adv Exp Med Biol. 2008; 637: 28–38.
 
7. Feng X, Liu J, Gong Y, Gou K, Yang H, Yuan Y, Xing C. DNA repair protein XPA is differentially expressed in colorectal cancer and predicts better prognosis.Cancer Med. 2018; 7(6):2339–2349.
 
8. Tao J, Zhuo ZJ, Su M, Yan L, He L, Zhang J. XPA gene polymorphisms and risk of neuroblastoma in Chinese children: a two-center case-control study. J Cancer, 2018;9(15): 2751-2756.
 
9. Hansen RD, Sørensen M, Tjønneland A, Overvad K, Wallin H, Raaschou-Nielsen, Vogel U. XPA A23G, XPC Lys939Gln, XPD Lys751Gln and XPD Asp312Asn polymorphisms, interactions with smoking, alcohol and dietary factors, and risk of colorectal cancer. Mutat Res, 2007; 619: 68–80.
 
10. Scharer OD. Nucleotide excision repair in eukaryotes, Cold Spring Harb Perspect Biol, 2013; 5(10):  a012609.
 
11. Sugitani N, Sivley RM, Perry KE, Capra JA, Chazin WJ. XPA: A key scaffold for human nucleotide excision repair. DNA Repair, 2016; 44: 123–135.
 
12. Bunick C, Miller M, Fuller B. Biochemical and structural domain analysis of xeroderma pigmentosum complementation group C protein. Biochemistry. 2006; 45(50): 14965–14979.
 
13. Friedberg EC, Bond JP, Burns DK, Cheo DL, Greenblatt MS, Meira LB, Nahari D, Reis AM. Defective nucleotide excision repair in xpc mu­tant mice and its association with cancer pre­disposition. Mutat Res, 2000; 459: 99-108.
 
14. Sands AT, Abuin A, Sanchez A, Conti CJ, Bradley A. High susceptibility to ultraviolet-induced car­cinogenesis in mice lacking XPC. Nature, 1995; 377: 162-165.
 
15. Marı´n MS, Lo´pez-Cima MF, Garcı´a-Castro L, Pascua T, Marro´n M, Tardo´n A. Poly (AT) Polymorphism in Intron 11 of the XPC DNA Repair Gene Enhances the Risk of Lung Cancer. Cancer Epidemiol Biomarkers Prev, 2004; 13: 1788-1795.
 
16. Liu Y, Wang H, Lin T, Wei Q, Zhi Y, Yuan Y, et al. Interactions between cigarette smoking and XPC-PAT genetic polymorphism enhance bladder cancer risk. Oncol Rep, 2012; 28: 337-345.
 
17. Hua RX, Zhu J, Jiang DH, Zhang SD, Zhang JB, Xue WQ, et al. Association of XPC Gene Polymorphisms with Colorectal Cancer Risk in a Southern Chinese Population: A Case-Control Study and Meta-Analysis. Genes, 2016; 73.
 
18. Sun HY, Zuo L, Zou JG, Zhang LF, Wu XP, Mi YY, et al. Current evidence on XPC rs2228001 A/C polymorphism and bladder cancer susceptibility. Int J Clin Exp Med, 2016; 9:2881-2888.
 
19. Paszkowska-Szczur K, Scott RJ, G´orski B. Polymorphisms in nucleotide excision repair genes and susceptibility to colorectal cancer in the Polish population. Mol Biol Rep, 2015; 42: 755–764.
 
20. Ahmad-Aizat AA, Siti-Nurfatimah MS, Aminudin MM, Ankathil R. XPC Lys939Gln polymorphism, smoking and risk of sporadic colorectal cancer among Malaysians. World J Gastroenterol. 2013; 19(23): 3623–3628.
 
21-Xiayi Ke, Collins A, Ye S. PIRA PCR designer for restriction analysis of single nucleotide polymorphisms. BIOINFORMATICS APPLICATIONS NOTE, 2001; 17(9):838–839.
 
22. Wu X, Zhao H, Wei Q, I Amos C, Zhang K, Guo Z, et al. XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis, 2003; 24: 505–509.
 
23. Rodriguez S, Gaunt TR, Day IN. Hardy-Weinberg Equilibrium Testing of Biological Ascertainment for Medline Randomization Studies. Am J Epidemiol, 2009; 169:505-514.
 
 
25. Hrdlickova B, Coutinho de Almeida R, Borek Z, Withoff S. Genetic variation in the non-coding genome: Involvement of micro-RNAs and long non-coding RNAs in disease. Biochimica et Biophysica Acta, 2014; 1842: 1910–1922.
 
26. Mehrzad J, Monajjemi M, Hashemi M. In silico Study of Effects of Polymorphisms on Biophysical Chemical Properties of Oxidized N-Terminal Domain of X-Ray Cross-Complementing Group 1 Protein. Biochem (Mosc), 2014; 79(1): 31-36.
 
27. Zhu JF, Chen YJ, Zhou JN. The single nucleotide polymorphism in the promoter of DNA repair gene XPA and in association with the risk of lung cancer. Zhong Liu, 2005; 25: 246–249.
 
28. Liu X, Lin Q, Fu C, Liu C, Zhu F, Liu Z, et al. Association between XPA gene rs1800975 polymorphism and susceptibility to lung cancer: a meta-analysis. Clin Respir J, 2018; 12:448–458.
 
29. He L, Deng, Luo H. XPA A23G polymorphism and risk of digestive system cancers: a meta-analysis. Onco Targets Ther, 2015; 8: 385–394.
 
30. Zhu J, Fu W, Jia W, Xia H, Liu GC, He J. Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk. Mol Ther Nucleic Acids, 2018; 12: 854-860.
 
31. Wu Y, Jin M, Liu B, Liang X, Yu Y, Li Q, et al. The association of XPC polymorphisms and tea drinking with colorectal cancer risk in a Chinese population. Mol Carcinog, 2011; 50:189–198.
 
32. Deng N, Zhou H, Fan H, Yuan Y. Single nucleotide polymorphisms and cancer susceptibility. Oncotarget. 2017; 8:110635-49.
 
1. Haggar FA, Robin P, Boushey M. Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors. Clin Colon AND Rectal Surg. 2009; 22(4): 191-197.
2. Basu AK. DNA Damage, Mutagenesis and Cancer. Int J Mol Sci. 2018; 19(4), 970.
3. Sugitani N, Shell SM, Soss SE, Chazin WJ. Redefining the DNA-binding domain of human XPA. J Am Chem Soc, 2014; 136(31): 10830-3.
4. Ziani SNagy ZAlekseev SSoutoglou EEgly JM, Coin F. Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin. J Cell Biol, 2014; 206: 589–598.
5. Park CH, Mu D, Reardon JT, Sancar A. The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor. J Biol Chem, 1995; 270: 4896–4902.
6. Camenisch U, Nageli H. XPA gene, its product and biological roles. Adv Exp Med Biol. 2008; 637: 28–38.
7. Feng X, Liu J, Gong Y, Gou K, Yang H, Yuan Y, Xing C. DNA repair protein XPA is differentially expressed in colorectal cancer and predicts better prognosis.Cancer Med. 2018; 7(6):2339–2349.
8. Tao J, Zhuo ZJ, Su M, Yan L, He L, Zhang J. XPA gene polymorphisms and risk of neuroblastoma in Chinese children: a two-center case-control study. J Cancer, 2018;9(15): 2751-2756.
9. Hansen RD, Sørensen M, Tjønneland A, Overvad K, Wallin H, Raaschou-Nielsen, Vogel U. XPA A23G, XPC Lys939Gln, XPD Lys751Gln and XPD Asp312Asn polymorphisms, interactions with smoking, alcohol and dietary factors, and risk of colorectal cancer. Mutat Res, 2007; 619: 68–80.
10. Scharer OD. Nucleotide excision repair in eukaryotes, Cold Spring Harb Perspect Biol, 2013; 5(10):  a012609.
11. Sugitani N, Sivley RM, Perry KE, Capra JA, Chazin WJ. XPA: A key scaffold for human nucleotide excision repair. DNA Repair, 2016; 44: 123–135.
12. Bunick C, Miller M, Fuller B. Biochemical and structural domain analysis of xeroderma pigmentosum complementation group C protein. Biochemistry. 2006; 45(50): 14965–14979.
13. Friedberg EC, Bond JP, Burns DK, Cheo DL, Greenblatt MS, Meira LB, Nahari D, Reis AM. Defective nucleotide excision repair in xpc mu­tant mice and its association with cancer pre­disposition. Mutat Res, 2000; 459: 99-108.
14. Sands AT, Abuin A, Sanchez A, Conti CJ, Bradley A. High susceptibility to ultraviolet-induced car­cinogenesis in mice lacking XPC. Nature, 1995; 377: 162-165.
15. Marı´n MS, Lo´pez-Cima MF, Garcı´a-Castro L, Pascua T, Marro´n M, Tardo´n A. Poly (AT) Polymorphism in Intron 11 of the XPC DNA Repair Gene Enhances the Risk of Lung Cancer. Cancer Epidemiol Biomarkers Prev, 2004; 13: 1788-1795.
16. Liu Y, Wang H, Lin T, Wei Q, Zhi Y, Yuan Y, et al. Interactions between cigarette smoking and XPC-PAT genetic polymorphism enhance bladder cancer risk. Oncol Rep, 2012; 28: 337-345.
17. Hua RX, Zhu J, Jiang DH, Zhang SD, Zhang JB, Xue WQ, et al. Association of XPC Gene Polymorphisms with Colorectal Cancer Risk in a Southern Chinese Population: A Case-Control Study and Meta-Analysis. Genes, 2016; 73.
18. Sun HY, Zuo L, Zou JG, Zhang LF, Wu XP, Mi YY, et al. Current evidence on XPC rs2228001 A/C polymorphism and bladder cancer susceptibility. Int J Clin Exp Med, 2016; 9:2881-2888.
19. Paszkowska-Szczur K, Scott RJ, G´orski B. Polymorphisms in nucleotide excision repair genes and susceptibility to colorectal cancer in the Polish population. Mol Biol Rep, 2015; 42: 755–764.
20. Ahmad-Aizat AA, Siti-Nurfatimah MS, Aminudin MM, Ankathil R. XPC Lys939Gln polymorphism, smoking and risk of sporadic colorectal cancer among Malaysians. World J Gastroenterol. 2013; 19(23): 3623–3628.
21-Xiayi Ke, Collins A, Ye S. PIRA PCR designer for restriction analysis of single nucleotide polymorphisms. BIOINFORMATICS APPLICATIONS NOTE, 2001; 17(9):838–839.
22. Wu X, Zhao H, Wei Q, I Amos C, Zhang K, Guo Z, et al. XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis, 2003; 24: 505–509.
23. Rodriguez S, Gaunt TR, Day IN. Hardy-Weinberg Equilibrium Testing of Biological Ascertainment for Medline Randomization Studies. Am J Epidemiol, 2009; 169:505-514.
25. Hrdlickova B, Coutinho de Almeida R, Borek Z, Withoff S. Genetic variation in the non-coding genome: Involvement of micro-RNAs and long non-coding RNAs in disease. Biochimica et Biophysica Acta, 2014; 1842: 1910–1922.
26. Mehrzad J, Monajjemi M, Hashemi M. In silico Study of Effects of Polymorphisms on Biophysical Chemical Properties of Oxidized N-Terminal Domain of X-Ray Cross-Complementing Group 1 Protein. Biochem (Mosc), 2014; 79(1): 31-36.
27. Zhu JF, Chen YJ, Zhou JN. The single nucleotide polymorphism in the promoter of DNA repair gene XPA and in association with the risk of lung cancer. Zhong Liu, 2005; 25: 246–249.
28. Liu X, Lin Q, Fu C, Liu C, Zhu F, Liu Z, et al. Association between XPA gene rs1800975 polymorphism and susceptibility to lung cancer: a meta-analysis. Clin Respir J, 2018; 12:448–458.
29. He L, Deng, Luo H. XPA A23G polymorphism and risk of digestive system cancers: a meta-analysis. Onco Targets Ther, 2015; 8: 385–394.
30. Zhu J, Fu W, Jia W, Xia H, Liu GC, He J. Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk. Mol Ther Nucleic Acids, 2018; 12: 854-860.
31. Wu Y, Jin M, Liu B, Liang X, Yu Y, Li Q, et al. The association of XPC polymorphisms and tea drinking with colorectal cancer risk in a Chinese population. Mol Carcinog, 2011; 50:189–198.
32. Deng N, Zhou H, Fan H, Yuan Y. Single nucleotide polymorphisms and cancer susceptibility. Oncotarget. 2017; 8:110635-49.