Abstract
The associations between four common genetic polymorphisms of transforming growth factor-β1 (TGF-β1 −509 C > T, +869 T > C, +915 G > C, and −800 G > A) and risk of colorectal tumor (including adenoma and cancer) have been widely studied. To date, no conclusions could be available because of controversial results reported. Thus, we conducted a meta-analysis to further assess the associations. We searched the databases of Medline, Embase, and Wangfang to identify eligible studies, and latest update was on January 1, 2012. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to present the associations. Our meta-analysis indicated that TGF-β1 −509 C > T, +869 T > C, +915 G > C, and -800 G > A were not associated with risk of colorectal adenoma (OR = 0.89 for C carriers vs. TT for −509 C > T, 1.03 for C carriers vs. TT for +869 T > C, 1.09 for C carriers vs. GG for +915 G > C, and 1.19 for A carriers vs. GG for 800 G > A). However, C allele of TGF-β1 −509 C > T and A allele of −800 G > A were associated with increased risk of colorectal cancer (CRC), and OR (95%CI) was 1.23 (0.99–1.52) for CC vs. TT for −509 C > T and 6.64 (3.46–12.72) for A carriers vs. GG. The positive association between −509 C allele and risk of CRC was more obvious when subgroup analyses were conducted for population-based and large sample-sized studies as well as Caucasians. In contrast, we did not observed any associations between TGF-β1 + 869 T > C, +915 G > C, and risk of CRC. This study indicated that C allele of TGF-β1 −509 C > T and A allele of −800 G > A might contribute to the increased risk of CRC, and could be used as two of genetic marks for screening individuals at high risk of CRC. Because of modest limitation, large sample-sized studies were required to confirm the findings.
Similar content being viewed by others
References
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA: a Canc J Clin. 2010;60:277–300.
Zhao P, Dai M, Chen W, Li N. Cancer trends in China. Jpn J Clin Oncol. 2010;40:281–5.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process—first American Cancer Society award lecture on cancer epidemiology and prevention. Cancer Res. 1992;52:6735–40.
Brevik A, Joshi AD, Corral R, Onland-Moret NC, Siegmund KD, Le Marchand L, et al. Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat. Cancer Epidemiol Biomarkers Prev. 2010;19:3167–73.
Yeh CC, Sung FC, Tang R, Chang-Chieh CR, Hsieh LL. Polymorphisms of cytochrome P450 1A2 and N-acetyltransferase genes, meat consumption, and risk of colorectal cancer. Dis Colon Rectum. 2009;52:104–11.
Massague J. TGF-beta in cancer. Cell. 2008;134:215–30.
Gordon KJ, Blobe GC. Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta. 2008;1782:197–228.
Inman GJ. Switching TGFβ from a tumor suppressor to a tumor promoter. Curr Opin Genet Dev. 2011;21:93–9.
Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet. 1999;8:93–7.
Slattery ML, Lundgreen A, Herrick JS, Wolff RK, Caan BJ. Genetic variation in the transforming growth factor-beta signaling pathway and survival after diagnosis with colon and rectal cancer. Cancer. 2011;117:4175–83.
Zhang Y, Liu B, Jin M, Ni Q, Liang X, Ma X, et al. Genetic polymorphisms of transforming growth factor-beta1 and its receptors and colorectal cancer susceptibility: a population-based case–control study in China. Cancer Lett. 2009;275:102–8.
Qi P, Ruan CP, Wang H, Zhou FG, Zhao YP, Gu X, et al. −509 C > T polymorphism in the TGF-beta1 gene promoter is not associated with susceptibility to and progression of colorectal cancer in Chinese. Colorectal Dis. 2010;12:1153–8.
Fang F, Yu L, Zhong Y, Yao L. TGFB1 509 C/T polymorphism and colorectal cancer risk: a meta-analysis. Med Oncol. 2010;27:1324–8.
Itzkowitz SH. Gastrointestinal adenomatous polyps. Semin Gastrointest Dis. 1996;7:105–16.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.
Sparks R, Bigler J, Sibert JG, Potter JD, Yasui Y, Ulrich CM. TGFbeta1 polymorphism (L10P) and risk of colorectal adenomatous and hyperplastic polyps. Int J Epidemiol. 2004;33:955–61.
Macarthur M, Sharp L, Hold GL, Little J, El-Omar EM. The role of cytokine gene polymorphisms in colorectal cancer and their interaction with aspirin use in the northeast of Scotland. Cancer Epidemiol Biomarkers Prev. 2005;14:1613–8.
Crivello A, Giacalone A, Vaglica M, Scola L, Forte GI, Macaluso MC, et al. Regulatory cytokine gene polymorphisms and risk of colorectal carcinoma. Ann N Y Acad Sci. 2006;1089:98–103.
Berndt SI, Huang WY, Chatterjee N, Yeager M, Welch R, Chanock SJ, et al. Transforming growth factor beta 1 (TGFB1) gene polymorphisms and risk of advanced colorectal adenoma. Carcinogenesis. 2007;28:1965–70.
Chung SJ, Kim JS, Jung HC, Song IS. Transforming growth factor-[beta]1–509T reduces risk of colorectal cancer, but not adenoma in Koreans. Cancer Sci. 2007;98:401–4.
Wei L, Chen F, Tan Z, Chen H. Association of TGF-beta 1 gene polymorphism with colorectal cancer. Zhong Liu. 2007;27:383–5.
Saltzman BS, Yamamoto JF, Decker R, Yokochi L, Theriault AG, Vogt TM, et al. Association of genetic variation in the transforming growth factor beta-1 gene with serum levels and risk of colorectal neoplasia. Cancer Res. 2008;68:1236–44.
Wu H, Fan Y, Liu W, He X, Zhu G, Zhu Z, et al. Transforming growth factor-beta 1 gene C-509T polymorphism and genetic susceptibility to colorectal cancer. Shi Jie Hua Ren Xiao Hua Za Zhi. 2008;16:4020–3.
Amirghofran Z, Jalali SA, Ghaderi A, Hosseini SV. Genetic polymorphism in the transforming growth factor beta1 gene ( −509 C/T and −800 G/A) and colorectal cancer. Cancer Genet Cytogenet. 2009;190:21–5.
Wu GY, Hasenberg T, Magdeburg R, Bonninghoff R, Sturm JW, Keese M. Association between EGF, TGF-beta1, VEGF gene polymorphism and colorectal cancer. World J Surg. 2009;33:124–9.
Forsti A, Li X, Wagner K, Tavelin B, Enquist K, Palmqvist R, et al. Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression. Gene Chromosome Canc. 2010;49:270–81.
Lee YS, Choi HB, Lee IK, Kim TG, Oh ST. Association between interleukin-4R and TGF-beta1 gene polymorphisms and the risk of colorectal cancer in a Korean population. Colorectal Dis. 2010;12:1208–12.
Yu Y, Chen C. Association of transforming growth factor beta 1 gene polymorphisms with colorectal cancer. Lin Chuang Nei Ke Za Zhi. 2010;27:490–3.
Yu Y, Chen C, Zhang J. Association between transforming growth factor beta1+915 G > C gene polymorphism and colorectal adenoma and carcinoma. Shi Yong Ai Zheng Za Zhi. 2010;25:571.
Attia J, Thakkinstian A, D'Este C. Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol. 2003;56:297–303.
Liu L, Zeng F, Wang K, Huang J, Xin L, Zhu PQ. Meta-analysis of the association between VEGF-634 G > C and risk of malignancy based on 23 case–control studies. J Cancer Res Clin Oncol. 2011;137:1027–36.
Zhuang W, Wu XT, Zhou Y, Liu L, Liu GJ, Wu TX, et al. Interleukin10–592 promoter polymorphism associated with gastric cancer among Asians: a meta-analysis of epidemiologic studies. Dig Dis Sci. 2010;55:1525–32.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.
Tsushima H, Kawata S, Tamura S, Ito N, Shirai Y, Kiso S, et al. High levels of transforming growth factor beta 1 in patients with colorectal cancer: association with disease progression. Gastroenterology. 1996;110:375–82.
Woo SU, Park KH, Woo OH, Yang DS, Kim AR, Lee ES, et al. Association of a TGF-beta1 gene −509 C/T polymorphism with breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2010;124:481–5.
Niu H, Niu Z, Zhang XL, Chen ZL. Absence of association between transforming growth factor B1 polymorphisms and gastric cancer: a meta-analysis. DNA Cell Biol. 2011. doi:10.1089/dna.2011.1426.
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Liu, Y., Zhou, W. & Zhong, DW. Meta-analyses of the associations between four common TGF-β1 genetic polymorphisms and risk of colorectal tumor. Tumor Biol. 33, 1191–1199 (2012). https://doi.org/10.1007/s13277-012-0364-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-012-0364-9