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Tumor Biology

, Volume 36, Issue 12, pp 9995–10002 | Cite as

TLR2∆22 (-196-174) significantly increases the risk of breast cancer in females carrying proline allele at codon 72 of TP53 gene: a case–control study from four ethnic groups of North Eastern region of India

  • K. Rekha Devi
  • Saia Chenkual
  • Gautam Majumdar
  • Jishan Ahmed
  • Tanvir Kaur
  • Jason C. Zonunmawia
  • Kaustab Mukherjee
  • Rup Kumar Phukan
  • Jagdish Mahanta
  • S.K. Rajguru
  • Debdutta Mukherjee
  • Kanwar Narain
Original Article

Abstract

Breast cancer (BC) is the second most common cancer in women. In the North Eastern Region (NER) of India, BC is emerging as an important concern as evidenced by the data available from population and hospital-based cancer registries. Studies on genetic susceptibility to BC are important to understand the increase in the incidence of BC in NER. The present case control study was conducted to investigate the association between tumour suppressor gene TP53 codon 72 polymorphism and innate immune pathway gene TLR2∆22 (-196-174) polymorphism with BC in females of NER of India for the identification of novel biomarker of BC. Four hundred sixty-two histopathologically confirmed BC cases from four states of NER of India, and 770 healthy controls were included by organizing community surveys from the neighbourhood of cases. In our study, no significant association between TP53 codon 72 polymorphisms and the risk of BC was found. However, our study has shown that TP53 codon 72 polymorphism is an important effect modifier. In the present study it was found that females carrying 22 base-pair deletion in the promoter region of their TLR2 gene had two times (AOR= 2.18, 95 % CI 1.13-4.21, p=0.019 in dominant model; AOR= 2.17, 95 % CI 1.09-4.34, p=0.027 in co-dominant model) increased risk of BC whwn they also carry proline allele at codon 72 of their TP53 gene.

Keywords

Transcription factor Cell cycle Apoptosis Inflammation Gene-gene interaction 

Notes

Acknowledgments

This work was supported by the Indian Council of Medical Research (ICMR), India. We would like to thank all study participants for their cooperation. We are grateful to the editorial board and esteemed referees of the journal ‘Tumor Biology’ for their critical comments to review the manuscript.

Conflict of interest

None.

References

  1. 1.
    Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–403.CrossRefPubMedGoogle Scholar
  2. 2.
    Kumar N, Pandey AN, Kumari S, Kishore S. Breast cancer associated with Von Recklinghausen's disease: case report and review of literature. Indian J Surg Oncol. 2014;5(3):205–7.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Amadou A, Hainaut P, Romieu I. Role of obesity in the risk of breast cancer: lessons from anthropometry. J Oncol. 2013;2013:906495.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Amadou A, Torres Mejia G, Fagherazzi G, Ortega C, Angeles-Llerenas A, Chajes V, et al. Anthropometry, silhouette trajectory, and risk of breast cancer in Mexican women. Am J Prev Med. 2014;46(3 Suppl 1):S52–64.CrossRefPubMedGoogle Scholar
  5. 5.
    Mathew A, Gajalakshmi V, Rajan B, Kanimozhi V, Brennan P, Mathew BS, et al. Anthropometric factors and breast cancer risk among urban and rural women in South India: a multicentric case–control study. Br J Cancer. 2008;99(1):207–13.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    McCormack VA, Mangtani P, Bhakta D, McMichael AJ, dos Santos SI. Heterogeneity of breast cancer risk within the South Asian female population in England: a population-based case–control study of first-generation migrants. Br J Cancer. 2004;90(1):160–6.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Opdahl S, Nilsen TI, Romundstad PR, Vanky E, Carlsen SM, Vatten LJ. Association of size at birth with adolescent hormone levels, body size and age at menarche: relevance for breast cancer risk. Br J Cancer. 2008;99(1):201–6.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    John EM, Phipps AI, Sangaramoorthy M. Body size, modifying factors, and postmenopausal breast cancer risk in a multiethnic population: the San Francisco Bay Area Breast Cancer Study. Springerplus. 2013;2(1):239.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Moorman PG, Terry PD. Consumption of dairy products and the risk of breast cancer: a review of the literature. Am J Clin Nutr. 2004;80(1):5–14.PubMedGoogle Scholar
  10. 10.
    Yaw YH, Shariff ZM, Kandiah M, Weay YH, Saibul N, Sariman S, et al. Diet and physical activity in relation to weight change among breast cancer patients. Asian Pac J Cancer Prev. 2014;15(1):39–44.CrossRefPubMedGoogle Scholar
  11. 11.
    Sangrajrang S, Chaiwerawattana A, Ploysawang P, Nooklang K, Jamsri P, Somharnwong S. Obesity, diet and physical inactivity and risk of breast cancer in Thai women. Asian Pac J Cancer Prev. 2013;14(11):7023–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Sjalander A, Birgander R, Hallmans G, Cajander S, Lenner P, Athlin L, et al. p53 polymorphisms and haplotypes in breast cancer. Carcinogenesis. 1996;17(6):1313–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Lauwen MM, Zwaveling S, de Quartel L, Ferreira Mota SC, Grashorn JA, Melief CJ, et al. Self-tolerance does not restrict the CD4+ T-helper response against the p53 tumor antigen. Cancer Res. 2008;68(3):893–900.CrossRefPubMedGoogle Scholar
  14. 14.
    Xie W, Wang Y, Huang Y, Yang H, Wang J, Hu Z. Toll-like receptor 2 mediates invasion via activating NF-kappaB in MDA-MB-231 breast cancer cells. Biochem Biophys Res Commun. 2009;379(4):1027–32. Epub 2009/01/15.CrossRefPubMedGoogle Scholar
  15. 15.
    Nischalke HD, Coenen M, Berger C, Aldenhoff K, Muller T, Berg T, et al. The toll-like receptor 2 (TLR2) -196 to −174 del/ins polymorphism affects viral loads and susceptibility to hepatocellular carcinoma in chronic hepatitis C. Int J Cancer. 2012;130(6):1470–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Mandal RK, George GP, Mittal RD. Association of Toll-like receptor (TLR) 2, 3 and 9 genes polymorphism with prostate cancer risk in North Indian population. Mol Biol Rep. 2012;39(7):7263–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Menendez D, Shatz M, Azzam K, Garantziotis S, Fessler MB, Resnick MA. The Toll-like receptor gene family is integrated into human DNA damage and p53 networks. PLoS Genet. 2011;7(3):e1001360.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Zhu L, Yuan H, Jiang T, Wang R, Ma H, Zhang S. Association of TLR2 and TLR4 polymorphisms with risk of cancer: a meta-analysis. PLoS One. 2013;8(12):e82858.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Sjalander A, Birgander R, Rannug A, Alexandrie AK, Tornling G, Beckman G. Association between the p21 codon 31 A1 (arg) allele and lung cancer. Hum Hered. 1996;46(4):221–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Franekova M, Zubor P, Stanclova A, Dussan CA, Bohusova T, Galo S, et al. Association of p53 polymorphisms with breast cancer: a case–control study in Slovak population. Neoplasma. 2007;54(2):155–61.PubMedGoogle Scholar
  21. 21.
    Frank AK, Leu JI, Zhou Y, Devarajan K, Nedelko T, Klein-Szanto A, et al. The codon 72 polymorphism of p53 regulates interaction with NF-{kappa}B and transactivation of genes involved in immunity and inflammation. Mol Cell Biol. 2011;31(6):1201–13.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Munoz-Fontela C, Pazos M, Delgado I, Murk W, Mungamuri SK, Lee SW, et al. p53 serves as a host antiviral factor that enhances innate and adaptive immune responses to influenza A virus. J Immunol. 2011;187(12):6428–36.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Li S, Wang L, Berman M, Kong YY, Dorf ME. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Immunity. 2011;35(3):426–40.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Theodoropoulos GE, Saridakis V, Karantanos T, Michalopoulos NV, Zagouri F, Kontogianni P, et al. Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development. Breast. 2012;21(4):534–8.CrossRefPubMedGoogle Scholar
  25. 25.
    de Oliveira MS, Santos MC, de Almeida PC, Panobianco MS, Fernandes AF. Evaluation of an educational handbook as a knowledge-acquisition strategy for mastectomized women. Rev Lat Am Enfermagem. 2012;20(4):668–76.CrossRefPubMedGoogle Scholar
  26. 26.
    Singh K, Singh VK, Agrawal NK, Gupta SK, Singh K. Association of Toll-like receptor 4 polymorphisms with diabetic foot ulcers and application of artificial neural network in DFU risk assessment in type 2 diabetes patients. Biomed Res Int. 2013;2013:318686.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Srivastava K, Srivastava A, Kumar A, Mittal B. Significant association between toll-like receptor gene polymorphisms and gallbladder cancer. Liver Int. 2010;30(7):1067–72.CrossRefPubMedGoogle Scholar
  28. 28.
    Shatz M, Menendez D, Resnick MA. The human TLR innate immune gene family is differentially influenced by DNA stress and p53 status in cancer cells. Cancer Res. 2012;72(16):3948–57.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Jordan JJ, Menendez D, Inga A, Noureddine M, Bell DA, Resnick MA. Noncanonical DNA motifs as transactivation targets by wild type and mutant p53. PLoS Genet. 2008;4(6):e1000104.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Malakar M, Devi KR, Phukan RK, Kaur T, Deka M, Puia L, et al. p53 codon 72 polymorphism interactions with dietary and tobacco related habits and risk of stomach cancer in Mizoram. India Asian Pac J Cancer Prev. 2014;15(2):717–23.CrossRefPubMedGoogle Scholar
  31. 31.
    Noma C, Miyoshi Y, Taguchi T, Tamaki Y, Noguchi S. Association of p53 genetic polymorphism (Arg72Pro) with estrogen receptor positive breast cancer risk in Japanese women. Cancer Lett. 2004;210(2):197–203.CrossRefPubMedGoogle Scholar
  32. 32.
    Singh V, Rastogi N, Mathur N, Singh K, Singh MP. Association of polymorphism in MDM-2 and p53 genes with breast cancer risk in Indian women. Ann Epidemiol. 2008;18(1):48–57.CrossRefPubMedGoogle Scholar
  33. 33.
    Weihrauch M, Bader M, Lehnert G, Wittekind C, Tannapfel A, Wrbitzky R. Carcinogen-specific mutation pattern in the p53 tumour suppressor gene in UV radiation-induced basal cell carcinoma. Int Arch Occup Environ Health. 2002;75(4):272–6.CrossRefPubMedGoogle Scholar
  34. 34.
    Alawadi S, Ghabreau L, Alsaleh M, Abdulaziz Z, Rafeek M, Akil N, et al. P53 gene polymorphisms and breast cancer risk in Arab women. Med Oncol. 2011;28(3):709–15.CrossRefPubMedGoogle Scholar
  35. 35.
    Kalemi TG, Lambropoulos AF, Gueorguiev M, Chrisafi S, Papazisis KT, Kotsis A. The association of p53 mutations and p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms with breast cancer in Northern Greece. Cancer Lett. 2005;222(1):57–65.CrossRefPubMedGoogle Scholar
  36. 36.
    Damin AP, Frazzon AP, Damin DC, Roehe A, Hermes V, Zettler C, et al. Evidence for an association of TP53 codon 72 polymorphism with breast cancer risk. Cancer Detect Prev. 2006;30(6):523–9.CrossRefPubMedGoogle Scholar
  37. 37.
    Keshava C, Frye BL, Wolff MS, McCanlies EC, Weston A. Waf-1 (p21) and p53 polymorphisms in breast cancer. Cancer Epidemiol Biomarkers Prev. 2002;11(1):127–30.PubMedGoogle Scholar
  38. 38.
    Suspitsin EN, Buslov KG, Grigoriev MY, Ishutkina JG, Ulibina JM, Gorodinskaya VM, et al. Evidence against involvement of p53 polymorphism in breast cancer predisposition. Int J Cancer. 2003;103(3):431–3.CrossRefPubMedGoogle Scholar
  39. 39.
    Mabrouk I, Baccouche S, El-Abed R, Mokdad-Gargouri R, Mosbah A, Said S, et al. No evidence of correlation between p53 codon 72 polymorphism and risk of bladder or breast carcinoma in Tunisian patients. Ann N Y Acad Sci. 2003;1010:764–70.CrossRefPubMedGoogle Scholar
  40. 40.
    Wang-Gohrke S, Rebbeck TR, Besenfelder W, Kreienberg R, Runnebaum IB. p53 germline polymorphisms are associated with an increased risk for breast cancer in German women. Anticancer Res. 1998;18(3B):2095–9.PubMedGoogle Scholar
  41. 41.
    Huang E, West M, Nevins JR. Gene expression profiling for prediction of clinical characteristics of breast cancer. Recent Prog Horm Res. 2003;58:55–73.CrossRefPubMedGoogle Scholar
  42. 42.
    Proestling K, Hebar A, Pruckner N, Marton E, Vinatzer U, Schreiber M. The Pro allele of the p53 codon 72 polymorphism is associated with decreased intratumoral expression of BAX and p21, and increased breast cancer risk. PLoS One. 2012;7(10):e47325.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Huang B, Zhao J, Li H, He KL, Chen Y, Chen SH, et al. Toll-like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Res. 2005;65(12):5009–14.CrossRefPubMedGoogle Scholar
  44. 44.
    Ferwerda G, Meyer-Wentrup F, Kullberg BJ, Netea MG, Adema GJ. Dectin-1 synergizes with TLR2 and TLR4 for cytokine production in human primary monocytes and macrophages. Cell Microbiol. 2008;10(10):2058–66.CrossRefPubMedGoogle Scholar
  45. 45.
    Matijevic T, Pavelic J. Toll-like receptors: cost or benefit for cancer? Curr Pharm Des. 2010;16(9):1081–90. Epub 2009/12/25.CrossRefPubMedGoogle Scholar
  46. 46.
    Galli R, Starace D, Busa R, Angelini DF, Paone A, De Cesaris P, et al. TLR stimulation of prostate tumor cells induces chemokine-mediated recruitment of specific immune cell types. J Immunol. 2010;184(12):6658–69. Epub 2010/05/21.CrossRefPubMedGoogle Scholar
  47. 47.
    Huang B, Zhao J, Shen S, Li H, He KL, Shen GX, et al. Listeria monocytogenes promotes tumor growth via tumor cell toll-like receptor 2 signaling. Cancer Res. 2007;67(9):4346–52. Epub 2007/05/08.CrossRefPubMedGoogle Scholar
  48. 48.
    Khvalevsky E, Rivkin L, Rachmilewitz J, Galun E, Giladi H. TLR3 signaling in a hepatoma cell line is skewed towards apoptosis. J Cell Biochem. 2007;100(5):1301–12. Epub 2007/01/24.CrossRefPubMedGoogle Scholar
  49. 49.
    He W, Liu Q, Wang L, Chen W, Li N, Cao X. TLR4 signaling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance. Mol Immunol. 2007;44(11):2850–9. Epub 2007/03/03.CrossRefPubMedGoogle Scholar
  50. 50.
    Pandey S, Mittal RD, Srivastava M, Srivastava K, Singh S, Srivastava S, et al. Impact of Toll-like receptors [TLR] 2 (-196 to -174 del) and TLR 4 (Asp299Gly, Thr399Ile) in cervical cancer susceptibility in North Indian women. Gynecol Oncol. 2009;114(3):501–5.CrossRefPubMedGoogle Scholar
  51. 51.
    Thuong NT, Hawn TR, Thwaites GE, Chau TT, Lan NT, Quy HT, et al. A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis. Genes Immun. 2007;8(5):422–8.CrossRefPubMedGoogle Scholar
  52. 52.
    Berzsenyi MD, Roberts SK, Preiss S, Woollard DJ, Beard MR, Skinner NA, et al. Hepatic TLR2 & TLR4 expression correlates with hepatic inflammation and TNF-alpha in HCV & HCV/HIV infection. J Viral Hepat. 2011;18(12):852–60.CrossRefPubMedGoogle Scholar
  53. 53.
    Xiang L, Zheng W, Kong B. Detection of PAX8 and p53 is beneficial in recognizing metastatic carcinomas in pelvic washings, especially in cases with suspicious cytology. Gynecol Oncol. 2012;127(3):595–600.CrossRefPubMedGoogle Scholar
  54. 54.
    Jegga AG, Inga A, Menendez D, Aronow BJ, Resnick MA. Functional evolution of the p53 regulatory network through its target response elements. Proc Natl Acad Sci U S A. 2008;105(3):944–9. Epub 2008/01/12.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • K. Rekha Devi
    • 1
  • Saia Chenkual
    • 2
  • Gautam Majumdar
    • 3
  • Jishan Ahmed
    • 4
  • Tanvir Kaur
    • 5
  • Jason C. Zonunmawia
    • 2
  • Kaustab Mukherjee
    • 1
  • Rup Kumar Phukan
    • 1
  • Jagdish Mahanta
    • 1
  • S.K. Rajguru
    • 1
  • Debdutta Mukherjee
    • 1
  • Kanwar Narain
    • 1
  1. 1.Regional Medical Research Centre, N.E. Region (Indian Council of Medical Research)DibrugarhIndia
  2. 2.Civil Hospital, Aizawl Upper BazarAizawlIndia
  3. 3.Regional Cancer CentreAgartalaIndia
  4. 4.Assam Medical College and HospitalDibrugarhIndia
  5. 5.Indian Council of Medical ResearchNew DelhiIndia

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