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TGFβ1 rs1800469 and SMAD4 rs10502913 polymorphisms and genetic susceptibility to colorectal cancer in Bangladeshi population

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Abstract

Background

Among Bangladeshi males and females, colorectal cancer is the fourth and fifth most prevalent cancer, respectively. Several studies have shown that the transforming growth factor beta 1 (TGFβ1) gene and SMAD4 gene have a great impact on colorectal cancer.

Objective

The present study aimed to investigate whether TGFβ1 rs1800469 and SMAD4 rs10502913 genetic polymorphisms are associated with susceptibility to colorectal cancer in the Bangladeshi population.

Methods and materials

This case–control study was performed on 167 colorectal cancer patients and 162 healthy volunteers, and polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method was employed for genotyping.

Results

In case of SMAD4 rs10502913 G > A polymorphism, the A allele reduced the colorectal cancer risk significantly (adjusted OR 0.35, 95% CI 0.23–0.52, p < 0.001) when compared to the G allele. It was also found that G/A and A/A genotypes of SMAD4 rs10502913 G > A polymorphism reduced the risk of colorectal cancer in comparison to the G/G genotype (G/A vs. G/G: adjusted OR 0.24, 95% CI 0.12–0.45, p < 0.001 and A/A vs. G/G: adjusted OR 0.06, 95% CI 0.02–0.21, p < 0.001). TGFβ1 rs1800469 C > T polymorphism showed an elevated risk of developing colorectal cancer, although the results were not statistically significant.

Conclusion

This study confirms the association of SMAD4 rs10502913 gene polymorphism with colorectal cancer susceptibility among the Bangladeshi population.

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Data availability

All data related to the manuscript were added to the manuscript main file, figure, and tables. The corresponding author will provide additional information on a valid request if required.

References

  1. Rawla P, Sunkara T, Barsouk A (2019) Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol 14(2):89–103. https://doi.org/10.5114/pg.2018.81072

    Article  CAS  Google Scholar 

  2. Colon Cancer Treatment, Symptoms, Prevention & Survival Rate. MedicineNet. Im Internet https://www.medicinenet.com/colon_cancer/article.htm. Accessed 30 Nov 2019

  3. Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. A Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492

    Article  Google Scholar 

  4. Hussain SA, Sullivan R (2013) Cancer control in Bangladesh. Jpn J Clin Oncol 43:1159–1169. https://doi.org/10.1093/jjco/hyt140

    Article  Google Scholar 

  5. Kuipers EJ, Grady WM, Lieberman D et al (2015) Colorectal cancer. Nat Rev Dis Primers 1:15065. https://doi.org/10.1038/nrdp.2015.65

    Article  Google Scholar 

  6. Karmokar PF, Shabnaz S, Aziz MA et al (2020) Variants of SMAD1 gene increase the risk of colorectal cancer in the Bangladeshi population. Tumour Biol. https://doi.org/10.1177/1010428320958955

    Article  Google Scholar 

  7. Mármol I, Sánchez-de-Diego C, Pradilla Dieste A et al (2017) Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int J Mol Sci. https://doi.org/10.3390/ijms18010197

    Article  Google Scholar 

  8. Yamagishi H, Kuroda H, Imai Y et al (2016) Molecular pathogenesis of sporadic colorectal cancers. Chin J Cancer. https://doi.org/10.1186/s40880-015-0066-y

    Article  Google Scholar 

  9. Stanilova S, Stanilov N, Julianov A et al (2018) Transforming growth factor-β1 gene promoter -509C/T polymorphism in association with expression affects colorectal cancer development and depends on gender. PLoS ONE 13:e0201775. https://doi.org/10.1371/journal.pone.0201775

    Article  CAS  Google Scholar 

  10. Massagué J (2008) TGFbeta in cancer. Cell 134:215–230. https://doi.org/10.1016/j.cell.2008.07.001

    Article  CAS  Google Scholar 

  11. Sheen Y, Kim M-J, Park S-A et al (2013) Targeting the transforming growth factor? Signaling in cancer therapy. Biomol Therapeut 21:323–331. https://doi.org/10.4062/biomolther.2013.072

    Article  CAS  Google Scholar 

  12. https://www.ncbi.nlm.nih.gov/snp/rs1800469

  13. Shah R, Hurley CK, Posch PE (2006) A molecular mechanism for the differential regulation of TGF-beta1 expression due to the common SNP-509C-T (c. -1347C > T). Hum Genet 120:461–469. https://doi.org/10.1007/s00439-006-0194-1

    Article  CAS  Google Scholar 

  14. Tsushima H, Kawata S, Tamura S et al (1996) High levels of transforming growth factor beta 1 in patients with colorectal cancer: association with disease progression. Gastroenterology 110:375–382. https://doi.org/10.1053/gast.1996.v110.pm8566583

    Article  CAS  Google Scholar 

  15. Shim KS, Kim KH, Han WS et al (1999) Elevated serum levels of transforming growth factor-beta1 in patients with colorectal carcinoma: its association with tumor progression and its significant decrease after curative surgical resection. Cancer 85:554–561. https://doi.org/10.1002/(sici)1097-0142(19990201)85:3%3c554::aid-cncr6%3e3.0.co;2-x

    Article  CAS  Google Scholar 

  16. Xiong B, Yuan H-Y, Hu M-B et al (2002) Transforming growth factor-beta1 in invasion and metastasis in colorectal cancer. World J Gastroenterol 8:674–678. https://doi.org/10.3748/wjg.v8.i4.674

    Article  CAS  Google Scholar 

  17. Wang Y, Yang H, Li L et al (2013) An updated meta-analysis on the association of TGF-β1 gene promoter -509C/T polymorphism with colorectal cancer risk. Cytokine 61:181–187. https://doi.org/10.1016/j.cyto.2012.09.014

    Article  CAS  Google Scholar 

  18. Wu G, Hasenberg T, Magdeburg R et al (2009) Association between EGF, TGF-β1, VEGF gene polymorphism and colorectal cancer. World J Surg 33:124–129. https://doi.org/10.1007/s00268-008-9784-5

    Article  Google Scholar 

  19. Qi P, Ruan C-P, Wang H et al (2010) −509C>T polymorphism in the TGF-β1 gene promoter is not associated with susceptibility to and progression of colorectal cancer in Chinese. Colorectal Dis 12:1153–1158. https://doi.org/10.1111/j.1463-1318.2009.02079.x

    Article  CAS  Google Scholar 

  20. Liu F (2001) SMAD4/DPC4 and pancreatic cancer survival: commentary re: M. Tascilar et al., The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res 7:4115–4121, (2001). Clin Cancer Res 7:3853–3856

  21. Derynck R, Gelbart WM, Harland RM et al (1996) Nomenclature: vertebrate mediators of TGFbeta family signals. Cell 87:173. https://doi.org/10.1016/s0092-8674(00)81335-5

    Article  CAS  Google Scholar 

  22. Wu D-M, Zhu H-X, Zhao Q-H et al (2010) Genetic variations in the SMAD4 gene and gastric cancer susceptibility. World J Gastroenterol 16:5635–5641. https://doi.org/10.3748/wjg.v16.i44.5635

    Article  CAS  Google Scholar 

  23. Massagué J, Blain SW, Lo RS (2000) TGFβ Signaling in Growth Control, Cancer, and Heritable Disorders. Cell 103:295–309. https://doi.org/10.1016/S0092-8674(00)00121-5

    Article  Google Scholar 

  24. Role of Transforming Growth Factor β in Human Disease | NEJM. https://doi.org/10.1056/nejm200005043421807. Accessed 31 Dec 2019

  25. SMAD4 as a Prognostic Marker in Colorectal Cancer | Clinical Cancer Research. https://clincancerres.aacrjournals.org/content/11/7/2606.short. Accessed 06 Jan 2020

  26. Jung B, Staudacher JJ, Beauchamp D (2017) Transforming growth factor β superfamily signaling in development of colorectal cancer. Gastroenterology 152:36–52. https://doi.org/10.1053/j.gastro.2016.10.015

    Article  CAS  Google Scholar 

  27. Cichy W, Klincewicz B, Plawski A (2014) Juvenile polyposis syndrome. Arch Med Sci 10:570–577. https://doi.org/10.5114/aoms.2014.43750

    Article  CAS  Google Scholar 

  28. Slattery ML, Herrick JS, Lundgreen A et al (2011) Genetic variation in the TGF-β signaling pathway and colon and rectal cancer risk. Cancer Epidemiol Biomarkers Prev 20:57–69. https://doi.org/10.1158/1055-9965.EPI-10-0843

    Article  CAS  Google Scholar 

  29. World Medical Association (2013) World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310:2191–2194. https://doi.org/10.1001/jama.2013.281053

    Article  CAS  Google Scholar 

  30. Chaity NI, Sultana TN, Hasan MM et al (2021) Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants influence smoking status in a Bangladeshi population. Pharmacol Rep 73:574–582. https://doi.org/10.1007/s43440-021-00243-1

    Article  CAS  Google Scholar 

  31. Jyoti SS, Islam F, Shrabonee II et al (2020) Prevalence of NPHS2 gene R229Q polymorphism in Bangladeshi children with nephrotic syndrome. Heliyon 6:e05317. https://doi.org/10.1016/j.heliyon.2020.e05317

    Article  CAS  Google Scholar 

  32. Sahaba SA, Rashid MA, Islam MS et al (2021) The link of ERCC2 rs13181 and ERCC4 rs2276466 polymorphisms with breast cancer in the Bangladeshi population. Mol Biol Rep. https://doi.org/10.1007/s11033-021-06994-7

    Article  Google Scholar 

  33. Liu HJ, Zhang QG, Wang YB, Xu HT, Zhang JJ (2015) TGF-β1-509C/T polymorphism and the risk of ESCC in a Chinese Han population. Int J Clin Exp Med 8(7):11524–11528

    CAS  Google Scholar 

  34. Derynck R, Akhurst RJ, Balmain A (2001) TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29:117–129. https://doi.org/10.1038/ng1001-117

    Article  CAS  Google Scholar 

  35. Kim BC, Kim HT, Park SH et al (2003) Fibroblasts from chronic wounds show altered TGF-beta-signaling and decreased TGF-beta type II receptor expression. J Cell Physiol 195:331–336

    Article  CAS  Google Scholar 

  36. Penn JW, Grobbelaar AO, Rolfe KJ (2012) The role of the TGF-β family in wound healing, burns and scarring: a review. Int J Burns Trauma 2:18–28

    CAS  Google Scholar 

  37. Klass BR, Grobbelaar AO, Rolfe KJ (2009) Transforming growth factor beta1 signalling, wound healing and repair: a multifunctional cytokine with clinical implications for wound repair, a delicate balance. Postgrad Med J 85:9–14. https://doi.org/10.1136/pgmj.2008.069831

    Article  CAS  Google Scholar 

  38. Poniatowski ŁA, Wojdasiewicz P, Gasik R et al (2015) Transforming growth factor beta family: insight into the role of growth factors in regulation of fracture healing biology and potential clinical applications. Mediators Inflamm 2015:e137823

    Article  Google Scholar 

  39. Miyaki M, Kuroki T (2003) Role of Smad4 (DPC4) inactivation in human cancer. Biochem Biophys Res Commun 306:799–804. https://doi.org/10.1016/S0006-291X(03)01066-0

    Article  CAS  Google Scholar 

  40. Berndt SI, Huang W-Y, Chatterjee N et al (2007) Transforming growth factor beta 1 (TGFB1) gene polymorphisms and risk of advanced colorectal adenoma. Carcinogenesis 28:1965–1970. https://doi.org/10.1093/carcin/bgm155

    Article  CAS  Google Scholar 

  41. Inman GJ (2011) Switching TGFβ from a tumor suppressor to a tumor promoter. Curr Opin Genet Dev 21:93–99. https://doi.org/10.1016/j.gde.2010.12.004

    Article  CAS  Google Scholar 

  42. Mishra L, Derynck R, Mishra B (2005) Transforming growth factor-beta signaling in stem cells and cancer. Science 310:68–71. https://doi.org/10.1126/science.1118389

    Article  CAS  Google Scholar 

  43. Padua D, Massagué J (2009) Roles of TGFbeta in metastasis. Cell Res 19:89–102. https://doi.org/10.1038/cr.2008.316

    Article  CAS  Google Scholar 

  44. Parkin DM, Bray F, Ferlay J et al (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156. https://doi.org/10.1002/ijc.1440

    Article  CAS  Google Scholar 

  45. Grady WM, Myeroff LL, Swinler SE et al (1999) Mutational inactivation of transforming growth factor β receptor type II in microsatellite stable colon cancers. Cancer Res 59:320–324

    CAS  Google Scholar 

  46. Grainger DJ, Heathcote K, Chiano M et al (1999) Genetic control of the circulating concentration of transforming growth factor type β1. Hum Mol Genet 8:93–97. https://doi.org/10.1093/hmg/8.1.93

    Article  CAS  Google Scholar 

  47. Gulubova M, Aleksandrova E, Vlaykova T (2018) Promoter polymorphisms in TGFB1 and IL10 genes influence tumor dendritic cells infiltration, development and prognosis of colorectal cancer. J Gene Med 20:e3005. https://doi.org/10.1002/jgm.3005

    Article  CAS  Google Scholar 

  48. Liu Y, Lin X-F, Lin C-J et al (2012) Transforming growth factor beta-1 C-509T polymorphism and cancer risk: a meta-analysis of 55 case-control studies. Asian Pac J Cancer Prev 13:4683–4688. https://doi.org/10.7314/APJCP.2012.13.9.4683

    Article  Google Scholar 

  49. Fang F, Yu L, Zhong Y et al (2010) TGFB1 509 C/T polymorphism and colorectal cancer risk: a meta-analysis. Med Oncol 27:1324–1328. https://doi.org/10.1007/s12032-009-9383-9

    Article  CAS  Google Scholar 

  50. Thiagalingam S, Lengauer C, Leach FS et al (1996) Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nat Genet 13:343–346. https://doi.org/10.1038/ng0796-343

    Article  CAS  Google Scholar 

  51. Zhao M, Mishra L, Deng C-X (2018) The role of TGF-β/SMAD4 signaling in cancer. Int J Biol Sci 14:111–123. https://doi.org/10.7150/ijbs.23230

    Article  CAS  Google Scholar 

  52. Wosiak A, Wodziński D, Michalska K et al (2021) Assessment of the role of selected SMAD3 and SMAD4 genes polymorphisms in the development of colorectal cancer: preliminary research. Pharmgenomics Pers Med 14:167–178. https://doi.org/10.2147/PGPM.S281958

    Article  Google Scholar 

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Acknowledgements

The authors are thankful to the Pharmacogenetics and Pharmacokinetics Laboratory of the Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Bangladesh.

Funding

This work received no research grant, and the Department of Clinical Pharmacy and Pharmacology, University of Dhaka, partially funded this project.

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh

    Taposhi Nahid Sultana, Nusrat Islam Chaity, Md. Mehedi Hasan, Sanzana Fareen Rivu, Mohd Nazmul Hasan Apu, Noor Ahmed Nahid & Md. Saiful Islam

  2. Department of Pharmacy, University of Asia Pacific, Dhaka, 1205, Bangladesh

    Taposhi Nahid Sultana

  3. Department of Pharmacy, Independent University, Bangladesh, Dhaka, 1229, Bangladesh

    Taposhi Nahid Sultana

  4. Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, 2200, Bangladesh

    Ishrat Islam Shrabonee

  5. Department of Pharmacy, Faculty of Science and Engineering, East West University, Dhaka, 1212, Bangladesh

    Sanzana Fareen Rivu

  6. Department of Pharmacy, Faculty of Pharmacy and Health Sciences, State University of Bangladesh, Dhaka, 1205, Bangladesh

    Md. Abdul Aziz & Shaid All Sahaba

  7. Department of Pharmacy, Faculty of Pharmacy, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh

    Mohammad Safiqul Islam

  8. Bangladesh Pharmacogenomics Research Network (BD-PGRN), Dhaka, Bangladesh

    Md. Abdul Aziz & Mohammad Safiqul Islam

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Contributions

MSI contributed to the study conception and design. Material preparation, data collection, and analysis were performed by TNS, NIC, MMH, IIS, and SFR. The first draft of the manuscript was written by TNS, NIC, and MMH. MAA, SAS, MNHA, NAN, and MSI commented and revised on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mohammad Safiqul Islam.

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None declared.

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Ethical approval was taken from the National Institute of Cancer Research and Hospital (NICRH), Dhaka, Bangladesh.

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Informed consent was obtained from all individual participants included in the study.

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Sultana, T.N., Chaity, N.I., Hasan, M.M. et al. TGFβ1 rs1800469 and SMAD4 rs10502913 polymorphisms and genetic susceptibility to colorectal cancer in Bangladeshi population. Mol Biol Rep 50, 1393–1401 (2023). https://doi.org/10.1007/s11033-022-08146-x

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