Advertisement

Molecular Biology Reports

, Volume 37, Issue 7, pp 3227–3232 | Cite as

TGFBR1*6A/9A polymorphism and cancer risk: a meta-analysis of 13,662 cases and 14,147 controls

  • Ru-Yan Liao
  • Chen Mao
  • Li-Xin Qiu
  • Hong Ding
  • Qing Chen
  • Hai-Feng Pan
Article

Abstract

Published data on the association between TGFBR1*6A/9A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 32 studies including 13,662 cases and 14,147 controls were involved in this meta-analysis. Overall, significantly elevated cancer risks were associated with TGFBR1*6A in all genetic models (for allelic effect: OR = 1.11; 95% CI = 1.03–1.21; for 6A/6A vs. 9A/9A: OR = 1.30; 95% CI = 1.01–1.69; for 9A/6A vs. 9A/9A: OR = 1.08; 95% CI = 1.01–1.15; for dominant model: OR = 1.08; 95% CI = 1.02–1.15; for recessive model: OR = 1.29; 95% CI = 1.00–1.68). In the subgroup analysis by cancer types, significant associations were found in breast cancer (for allelic effect: OR = 1.16; 95% CI = 1.01–1.34) and ovarian cancer (for allelic effect: OR = 1.24; 95% CI = 1.00–1.54; for 6A/6A vs. 9A/9A: OR = 2.34; 95% CI = 1.03–5.33). However, no significant associations were found in colorectal cancer, bladder cancer, prostate cancer and lung cancer for all genetic models. In summary, this meta-analysis suggests that the TGFBR1*6A/9A polymorphism is associated with cancer susceptibility, increasing the risk of breast and ovarian cancer.

Keywords

TGFBR1 Polymorphism Cancer Susceptibility Meta-analysis 

References

  1. 1.
    Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW (2008) An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat 107:309–330CrossRefPubMedGoogle Scholar
  2. 2.
    Karim-Kos HE, De Vries E, Soerjomataram I, Lemmens V, Siesling S, Coebergh JW (2008) Recent trends of cancer in Europe: a combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s. Eur J Cancer 44:1345–1389CrossRefPubMedGoogle Scholar
  3. 3.
    Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85CrossRefPubMedGoogle Scholar
  4. 4.
    Ebner R, Chen RH, Shum L, Lawler S, Zioncheck TF, Lee A (1993) Cloning of a type I TGF-β receptor and its effect on TGF-β binding to the type II receptor. Science 260:1344–1348CrossRefPubMedGoogle Scholar
  5. 5.
    Pasche B, Kolachana P, Nafa K, Satagopan J, Chen YG, Lo RS (1999) TbetaR-I (6A) is a candidate tumor susceptibility allele. Cancer Res 59:5678–5682PubMedGoogle Scholar
  6. 6.
    Chen T, de Vries EG, Hollema H, Yegen HA, Vellucci VF, Strickler HD (1999) Structural alterations of transforming growth factor-beta receptor genes in human cervical carcinoma. Int J Cancer 82:43–51CrossRefPubMedGoogle Scholar
  7. 7.
    van Tilborg AA, de Vries A, Zwarthoff EC (2001) The chromosome 9q genes TGFBR1, TSC1, and ZNF189 are rarely mutated in bladder cancer. J Pathol 194:76–80CrossRefPubMedGoogle Scholar
  8. 8.
    Stefanovska AM, Efremov GD, Dimovski AJ, Jasar D, Zografski G, Josifovski T (2001) TbetaR-I(6A) polymorphism is not a tumor susceptibility allele in Macedonian colorectal cancer patients. Correspondence re: B. Pasche et al. Type I TbetaR-I (6A) Is a candidate tumor susceptibility allele. Cancer Res., 58:2727–2732, 1998. Cancer Res 61:8351–8352PubMedGoogle Scholar
  9. 9.
    Samowitz WS, Curtin K, Leppert MF, Slattery ML (2001) Uncommon TGFBRI allele is not associated with increased susceptibility to colon cancer. Genes Chromosom Cancer 32:381–383CrossRefPubMedGoogle Scholar
  10. 10.
    Baxter SW, Choong DY, Eccles DM, Campbell IG (2002) Transforming growth factor beta receptor 1 polyalanine polymorphism and exon 5 mutation analysis in breast and ovarian cancer. Cancer Epidemiol Biomarkers Prev 11:211–214PubMedGoogle Scholar
  11. 11.
    Chen T, Jackson C, Costello B, Singer N, Colligan B, Douglass L (2004) An intronic variant of the TGFBR1 gene is associated with carcinomas of the kidney and bladder. Int J Cancer 112:420–425CrossRefPubMedGoogle Scholar
  12. 12.
    Kaklamani V, Baddi L, Rosman D, Liu J, Ellis N, Oddoux C (2004) No major association between TGFBR1*6A and prostate cancer. BMC Genet 5:28CrossRefPubMedGoogle Scholar
  13. 13.
    Pasche B, Kaklamani VG, Hou N, Young T, Rademaker A, Peterlongo P (2004) TGFBR1*6A and cancer: a meta-analysis of 12 case–control studies. J Clin Oncol 22:756–758CrossRefPubMedGoogle Scholar
  14. 14.
    Jin Q, Hemminki K, Grzybowska E, Klaes R, Söderberg M, Zientek H (2004) Polymorphisms and haplotype structures in genes for transforming growth factor beta1 and its receptors in familial and unselected breast cancers. Int J Cancer 112:94–99CrossRefPubMedGoogle Scholar
  15. 15.
    Suarez BK, Pal P, Jin CH, Kaushal R, Sun G, Jin L (2005) TGFBR1*6A is not associated with prostate cancer in men of European ancestry. Prostate Cancer Prostatic Dis 8:50–53CrossRefPubMedGoogle Scholar
  16. 16.
    Spillman MA, Schildkraut JM, Halabi S, Moorman P, Calingaert B, Bentley RC (2005) Transforming growth factor beta receptor I polyalanine repeat polymorphism does not increase ovarian cancer risk. Gynecol Oncol 97:543–549CrossRefPubMedGoogle Scholar
  17. 17.
    Kaklamani VG, Baddi L, Liu J, Rosman D, Phukan S, Bradley C (2005) Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk. Cancer Res 65:3454–3461PubMedGoogle Scholar
  18. 18.
    Chen T, Jackson CR, Link A, Markey MP, Colligan BM, Douglass LE (2006) Int7G24A variant of transforming growth factor-beta receptor type I is associated with invasive breast cancer. Clin Cancer Res 12:392–397CrossRefPubMedGoogle Scholar
  19. 19.
    Feigelson HS, Patel AV, Diver WR, Stevens VL, Thun MJ, Calle EE (2006) Transforming growth factor beta receptor type I and transforming growth factor beta1 polymorphisms are not associated with postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 15:1236–1237CrossRefPubMedGoogle Scholar
  20. 20.
    You W, Liu Z, Zhao J, Zheng M, Zheng SY, Liu X (2007) No association between TGFBR1*6A and lung cancer. J Thorac Oncol 2:657–659CrossRefPubMedGoogle Scholar
  21. 21.
    Cox DG, Penney K, Guo Q, Hankinson SE, Hunter DJ (2007) TGFB1 and TGFBR1 polymorphisms and breast cancer risk in the Nurses’ Health Study. BMC Cancer 7:175CrossRefPubMedGoogle Scholar
  22. 22.
    Song B, Margolin S, Skoglund J, Zhou X, Rantala J, Picelli S (2007) TGFBR1*6A and Int7G24A variants of transforming growth factor-beta receptor 1 in Swedish familial and sporadic breast cancer. Br J Cancer 97:1175–1179CrossRefPubMedGoogle Scholar
  23. 23.
    Skoglund J, Song B, Dalén J, Dedorson S, Edler D, Hjern F (2007) Lack of an association between the TGFBR1*6A variant and colorectal cancer risk. Clin Cancer Res 13:3748–3752CrossRefPubMedGoogle Scholar
  24. 24.
    Skoglund Lundin J, Vandrovcova J, Song B, Zhou X, Zelada-Hedman M, Werelius B (2009) TGFBR1 variants TGFBR1*6A and Int7G24A are not associated with an increased familial colorectal cancer risk. Br J Cancer 100:1674–1679CrossRefPubMedGoogle Scholar
  25. 25.
    Castillejo A, Rothman N, Murta-Nascimento C, Malats N, García-Closas M, Gómez-Martínez A (2009) TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis. Int J Cancer 124:608–613CrossRefPubMedGoogle Scholar
  26. 26.
    Jakubowska A, Gronwald J, Menkiszak J, Górski B, Huzarski T, Byrski T (2009) BRCA1-associated breast and ovarian cancer risks in Poland: no association with commonly studied polymorphisms. Breast Cancer Res TreatGoogle Scholar
  27. 27.
    Colleran G, McInerney N, Rowan A, Barclay E, Jones AM, Curran C (2009) The TGFBR1*6A/9A polymorphism is not associated with differential risk of breast cancer. Breast Cancer Res TreatGoogle Scholar
  28. 28.
    Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129CrossRefGoogle Scholar
  29. 29.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRefPubMedGoogle Scholar
  30. 30.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMedGoogle Scholar
  31. 31.
    Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 8:15–17Google Scholar
  32. 32.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedGoogle Scholar
  33. 33.
    Siegel PM, Massague J (2003) Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer 3:807–820CrossRefPubMedGoogle Scholar
  34. 34.
    Jakowlew SB (2006) Transforming growth factor-b in cancer metastasis. Cancer Metastasis Rev 25:435–457CrossRefPubMedGoogle Scholar
  35. 35.
    Bian Y, Kaklamani V, Reich J, Pasche B (2003) TGF-beta signaling alterations in cancer. Cancer Treat Res 115:73–94CrossRefPubMedGoogle Scholar
  36. 36.
    Ziv E, Cauley J, Morin PA, Saiz R, Browner WS (2001) Association between the T29-->C polymorphism in the transforming growth factor beta1 gene and breast cancer among elderly white women: the study of osteoporotic fractures. JAMA 285:2859–2863CrossRefPubMedGoogle Scholar
  37. 37.
    Marchand LL, Haiman CA, van den Berg D, Wilkens LR, Kolonel LN, Henderson BE (2004) T29C polymorphism in the transforming growth factor h1 gene and postmenopausal breast cancer risk: the Multiethnic Cohort Study. Cancer Epidemiol Biomarkers Prev 13:412–415PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Ru-Yan Liao
    • 1
  • Chen Mao
    • 1
  • Li-Xin Qiu
    • 2
  • Hong Ding
    • 3
  • Qing Chen
    • 1
  • Hai-Feng Pan
    • 4
  1. 1.Department of Epidemiology, School of Public Health and Tropical MedicineSouthern Medical UniversityGuangzhouChina
  2. 2.Cancer Center, Nanjing Drum Tower HospitalNanjing Medical UniversityNanjingChina
  3. 3.Longgang Center for Disease Control and Prevention of ShenzhenShenzhenChina
  4. 4.Department of Epidemiology and Biostatistics, School of Public HealthAnhui Medical UniversityHefeiChina

Personalised recommendations