Novel Candidate Single Nucleotide Polymorphisms of ERCC2 Gene that Influence Colorectal Cancer Susceptibility
DOI:
https://doi.org/10.31351/vol33iss3pp187-194Keywords:
Cancer risk, colorectal cancer, SNPs, NER pathway, XPDAbstract
Colorectal cancer (CRC) is the most common gastrointestinal malignancy and one of the top ten common cancers worldwide with approximately 2 million cases. There are multiple risk factors that could lead to CRC emergence; of which are genetic polymorphisms. Excision repair cross-complementing group 2 (ERCC2) gene encodes for ERCC2 enzyme which plays a crucial role in maintaining genomic integrity by removing DNA adducts. Several studies suggested that there could be a link between genetic polymorphisms of ERCC2 gene and the risk of CRC development. Hence the present study aims to validate the relationship between the following ERCC2 single nucleotide polymorphisms (rs13181, rs149943175, rs530662943, and rs1799790) and CRC susceptibility. A total of 121 participants were enrolled in this case control study; 72 CRC patients and 49 apparently healthy individuals. Genotyping was performed using polymerase chain reaction (PCR) followed by sequencing then the association between genetic polymorphisms and CRC susceptibility was examined. GA genotype and A allele of rs149943175 were associated with lower risk of CRC development. However, GA genotype and A allele carriers of rs530662943 had significantly increased risk compared to GG genotype. Additional stratified analyses showed that carriers of heterozygous genotype of rs149943175 who non-smokers, females or BMI figures less than 25 are less likely to develop CRC compared to wild genotype carriers. Taken together, genetic polymorphisms of ERCC2 modulate the susceptibility of CRC malignancy.
Received 29/7/2023
Accepted 11/10/2023
Published 15/9/2024
References
References
Cordes LM CS. Cancer: The Disease and Treatment. In: DiPiro JT YG, Michael Posey L, Haines ST, Nolin TD, Ellingrod VL, editor. DiPiro: Pharmacotherapy A Pathophysiologic Approach. 12 ed. New York: McGraw Hill; 2021.
World Health Organization. Cancer 2022 [Available from: https://www.who.int/news-room/fact-sheets/detail/cancer.Accessed March 2023.
Hossain MS, Karuniawati H, Jairoun AA, Urbi Z, Ooi J, John A, et al. Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies. Cancers (Basel). 2022;14(7).
Al Alwan NA. Cancer control and oncology care in Iraq. In: Al-Shamsi HO A-GI, Iqbal F, Al-Awadhi A, editor. Cancer in the Arab World. 8. Journal of Contemporary Medical Sciences: Springer; 2022. p. 82-5.
Bardhan K, Liu K. Epigenetics and colorectal cancer pathogenesis. Cancers. 2013;5(2):676-713.
Mahmood AH, Zeiny SM, Mahmood AS. Serological markers “CEA test & sAPRIL test” in Iraqi patients with colon cancer. Journal of the Faculty of Medicine Baghdad. 2017;59(4):317-20.
Dhahir NK, Noaman, A. A. A Comparative Study of Colorectal Cancer Based on Patient’s Age. Journal of the faculty of medicine Baghdad. 2021;63(2):70-3.
Dekker E, Tanis PJ, Vleugels J, Kasi PM, Wallace M. Pure-AMC. Lancet. 2019;394:1467-80.
Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nature reviews Gastroenterology & hepatology. 2019;16(12):713-32.
Hanon BM, Al-Mohaimen Mohammad NA, Mahmood AS. CpG Island Methylator Phenotype (CIMP) Correlation with Clinical and Morphological Feature of Colorectal Cancer in Iraq patients. Pan Arab Journal of Oncology. 2015;8(2).
Mahood WS, Nadir MI, Tobal K, Asker BA. Methylation Status of p16 gene in Iraqi Colorectal Cancer Patients. Iraqi journal of biotechnology. 2014;13(2):237-47.
Karim SK, Majeed BAAA, Nader MI. ERCC1 C118T polymorphism has predictive risk value for breast cancer in patients received platinum-based chemotherapy as the adjuvant treatment. European Journal of Biomedical. 2016;3(9):551-3.
Alhmoud JF, Woolley JF, Al Moustafa A-E, Malki MI. DNA damage/repair management in cancers. Cancers. 2020;12(4):1050.
Wu K-G, He X-F, Li Y-H, Xie W-B, Huang X. Association between the XPD/ERCC2 Lys751Gln polymorphism and risk of cancer: evidence from 224 case–control studies. Tumor Biology. 2014;35:11243-59.
Sameer AS, Nissar S. XPD–The Lynchpin of NER: Molecule, Gene, Polymorphisms, and Role in Colorectal Carcinogenesis. Frontiers in Molecular Biosciences. 2018;5:23.
Li M, Zhao Y, Zhao E, Wang K, Lu W, Yuan L. Predictive value of two polymorphisms of ERCC2, rs13181 and rs1799793, in clinical outcomes of chemotherapy in gastric cancer patients: a meta-analysis. Disease Markers. 2018;2018.
Yi C, Li T, Shen Y, Wang P, Dai L, Shi J, et al. Polymorphisms of nucleotide excision repair genes associated with colorectal cancer risk: Meta-analysis and trial sequential analysis. Front Genet. 2022;13:1009938.
Salimzadeh H, Lindskog EB, Gustavsson B, Wettergren Y, Ljungman D. Association of DNA repair gene variants with colorectal cancer: risk, toxicity, and survival. BMC Cancer. 2020;20(1):409.
Paszkowska-Szczur K, Scott RJ, Górski B, Cybulski C, Kurzawski G, Dymerska D, et al. Polymorphisms in nucleotide excision repair genes and susceptibility to colorectal cancer in the Polish population. Molecular biology reports. 2015;42:755-64.
Balkan E, Bilici M, Gundogdu B, Aksungur N, Kara A, Yasar E, et al. ERCC2 Lys751Gln rs13181 and XRCC2 Arg188His rs3218536 gene polymorphisms contribute to susceptibility of colon, gastric, liver, lung and prostate cancer. Journal Of Buon. 2020;25(1):574-81.
Farhad R, Saleh ES, Alsammarraie AZ. No evidence of relationship between colorectal cancer susceptibility and ERCC2 gene polymorphisms.
Saleh Khudhur S, Saadi Saleh E, Hadi Alosami M, G. Shareef L. Association between polymorphisms within the gene coding for tumor necrosis factor (TNF)-alpha with outcomes of treatment in a sample of Iraqi patients with ankylosing spondylitis taking etanercept: an observational study. F1000Research. 2022;11:1576.
Khudhur SS, Saleh ES, Alosami MH. The impact of rs767455 and rs1061622 polymorphisms on treatment outcomes in Iraqi ankylosing spondylitis patients taking etanercept. The Egyptian Journal of Hospital Medicine. 2023;90(2):3488-94.
Kathem SH. The prevalence of UGT1A1* 93 and ABCC5 polymorphisms in cancer patients receiving irinotecan-based chemotherapy at Al-Najaf Al-Ashraf. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2019;28(2):24-9.
Mohammed NS, Rasheed MK, Ghali HH, Ahmed SJ. Detection of Thiopurine S-Methyltransferase (TPMT) Polymorphisms TPMT* 3A, TPMT* 3B and TPMT* 3C in Children with Acute Lymphoblastic Leukemia. Journal of the Faculty of Medicine Baghdad. 2018;60(3):166-71.
Alrubaie A, Alkhalidi N, Abd-Alhusain S. A clinical study of newly-diagnosed colorectal cancer over 2 years in a gastroenterology center in Iraq. Journal of Coloproctology (Rio de Janeiro). 2019;39:217-22.
Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, et al. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
Manuguerra M, Saletta F, Karagas MR, Berwick M, Veglia F, Vineis P, et al. XRCC3 and XPD/ERCC2 single nucleotide polymorphisms and the risk of cancer: a HuGE review. American journal of epidemiology. 2006;164(4):297-302.
Buch SC, Diergaarde B, Nukui T, Day RS, Siegfried JM, Romkes M, et al. Genetic variability in DNA repair and cell cycle control pathway genes and risk of smoking-related lung cancer. Mol Carcinog. 2012;51 Suppl 1(Suppl 1):E11-20.
Jasiem TM, Al-Hussaini RMA-H. The Impact of the ERCC2 Lys751Gln Polymorphism on the Risk of Acute Myeloid Leukemia in an Iraqi Patients. J Contemp Med Sci| Vol. 2023;9(1):24-7.
Al-Ward MA, Jawad MM. Study of Multiple Genotypes in the XPD gene for A/C Lys751Gln and Lung Cancer in Samples from Baghdad–Iraq. Prof(Dr) RK Sharma. 2021;21(1):1727.
Canbay E, Cakmakoglu B, Zeybek U, Sozen S, Cacina C, Gulluoglu M, et al. Association of APE1 and hOGG1 polymorphisms with colorectal cancer risk in a Turkish population. Current medical research and opinion. 2011;27(7):1295-302.
Gómez-Díaz B, de la Luz Ayala-Madrigal M, Gutiérrez-Angulo M, Valle-Solis AE, Linares-González LM, González-Guzmán R, et al. Analysis of ERCC1 and ERCC2 gene variants in osteosarcoma, colorectal and breast cancer. Oncology Letters. 2015;9(4):1657-61.
Moghtit FZ, Aberkane MS, Le Morvan V, Louhibi L, Bellot R, Bousahba A, et al. No association between XRCC3 Thr241Met and XPD Lys751Gln polymorphisms and the risk of colorectal cancer in West Algerian population: a case–control study. Medical Oncology. 2014;31:1-7.
Sliwinski T, Krupa R, Wisniewska-Jarosinska M, Pawlowska E, Lech J, Chojnacki J, et al. Common polymorphisms in the XPD and hOGG1 genes are not associated with the risk of colorectal cancer in a Polish population. The Tohoku journal of experimental medicine. 2009;218(3):185-91.
Ni M, Zhang W-z, Qiu J-r, Liu F, Li M, Zhang Y-j, et al. Association of ERCC1 and ERCC2 polymorphisms with colorectal cancer risk in a Chinese population. Scientific reports. 2014;4(1):1-4.
Gul S, Khan A, Raza A, Khan I, Ehtisham S. Association of XPD Lys751Gln gene polymorphism with susceptibility and clinical outcome of colorectal cancer in Pakistani population: a case–control pharmacogenetic study. Genes & Genomics. 2020;42:1389-98.
Jin D, Zhang M, Hua H. Impact of polymorphisms in DNA repair genes XPD, hOGG1 and XRCC4 on colorectal cancer risk in a Chinese Han Population. Bioscience reports. 2019;39(1).
Kamiza AB, Hsieh LL, Tang R, Chien HT, Lai CH, Chiu LL, et al. Polymorphisms of DNA repair genes are associated with colorectal cancer in patients with Lynch syndrome. Molecular genetics & genomic medicine. 2018;6(4):533-40.
Chen J, Iverson D. Estrogen in obesity-associated colon cancer: friend or foe? Protecting postmenopausal women but promoting late-stage colon cancer. Cancer Causes & Control. 2012;23:1767-73.
Steri M, Idda ML, Whalen MB, Orrù V. Genetic variants in mRNA untranslated regions. Wiley Interdisciplinary Reviews: RNA. 2018;9(4):e1474.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Iraqi Journal of Pharmaceutical Sciences( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512)
This work is licensed under a Creative Commons Attribution 4.0 International License.
