Evaluation of a variant in the transcription factor 7-like 2 (TCF7L2) gene and prostate cancer risk in a population-based study†
Ilir Agalliu
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
Search for more papers by this authorMiia Suuriniemi
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Search for more papers by this authorLudmila Prokunina-Olsson
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Search for more papers by this authorBo Johanneson
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Search for more papers by this authorFrancis S. Collins
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Search for more papers by this authorJanet L. Stanford
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington
Search for more papers by this authorCorresponding Author
Elaine A. Ostrander
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Room 5351, Bethesda, MD 20892.Search for more papers by this authorIlir Agalliu
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
Search for more papers by this authorMiia Suuriniemi
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Search for more papers by this authorLudmila Prokunina-Olsson
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Search for more papers by this authorBo Johanneson
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Search for more papers by this authorFrancis S. Collins
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Search for more papers by this authorJanet L. Stanford
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington
Search for more papers by this authorCorresponding Author
Elaine A. Ostrander
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Room 5351, Bethesda, MD 20892.Search for more papers by this authorIlir Agalliu and Miia Suuriniemi are contributed equally to this work.
Abstract
Background
Transcription factor 7-like 2 (TCF7L2) is a high mobility group-box containing protein that is a critical member of the Wnt/β-catenin canonical signaling pathway. In addition to its recently recognized role in diabetes, aberrant TCF7L2 expression has been implicated in cancer through regulation of cell proliferation and apoptosis by c-MYC and cyclin D. It has been hypothesized that germline variants within the TCF7L2 gene previously associated with diabetes may affect cancer risk through the Wnt/β-catenin signaling pathway. Specifically, the same risk allele of single nucleotide polymorphism (SNP) rs12255372 that is associated with diabetes (T allele) has recently been associated with an increased risk of breast cancer.
Methods
Here, we investigated associations between rs12255372 and prostate cancer risk among 1,457 cases and 1,351 controls from a population-based study.
Results
The variant TT genotype was not associated with overall prostate cancer risk. However, there was evidence that men homozygous for the variant T allele had an elevated relative risk of more aggressive prostate cancer, as defined by high Gleason score (OR = 1.7, 95% CI = 1.0–2.8) or regional/distant stage (OR = 1.7, 95% CI = 1.1–2.6) disease.
Conclusions
Our findings suggest that this variant in the TCF7L2 gene may be associated with risk of developing more clinically significant disease. These results need to be confirmed, but provide initial evidence that the TCF7L2 gene may alter risk of developing more aggressive prostate cancer. Prostate 68: 740–747, 2008. © 2008 Wiley-Liss, Inc.
REFERENCES
- 1 Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin 2007; 57: 43–66.
- 2 Steinberg GD, Carter BS, Beaty TH, Childs B, Walsh PC. Family history and the risk of prostate cancer. Prostate 1990; 17: 337–347.
- 3 Spitz MR, Currier RD, Fueger JJ, Babaian RJ, Newell GR. Familial patterns of prostate cancer: A case control analysis. J Urol 1991; 146: 1305–1307.
- 4 Whittemore A, Wu A, Kolonel L, John E, Gallagher R, Howe G, West D, Teh C, Stamey T. Family history and prostate cancer risk in black, white, and Asian men in the United States and Canada. Am J Epidemiol 1995; 141: 732–740.
- 5 Hayes RB, Liff JM, Pottern LM, Greenberg RS, Schoenberg JB, Schwarz AG, Swanson M, Silverman DT, Morris-Brown L, Hoover RN, Fraumeni JF. Prostate cancer risk in US blacks and whites with a family history of cancer. Int J Cancer 1995; 60: 361–364.
- 6
Ghadirian P,
Howe GR,
Hislop TG,
Maisonneuve P.
Family history of prostate cancer: A multi-center case-control study in Canada.
Int J Cancer
1997;
70:
679–681.
10.1002/(SICI)1097-0215(19970317)70:6<679::AID-IJC9>3.0.CO;2-S CAS PubMed Web of Science® Google Scholar
- 7 Cerhan JR, Parker AS, Putnam SD, Chiu BC, Lynch CF, Cohen MB, Torner JC, Cantor KP. Family history and prostate cancer risk in a population-based cohort of Iowa men. Cancer Epidemiol Biomarkers Prev 1999; 8: 53–60.
- 8 Goldgar DE, Easton DF, Cannon-Albright LA, Skolnick MH. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst 1994; 86: 1600–1608.
- 9 Verhage BA, Kiemeney LA. Genetic susceptibility to prostate cancer: A review. Fam Cancer 2003; 2: 57–67.
- 10 Ostrander EA, Kwon EM, Stanford JL. Genetic susceptibility to aggressive prostate cancer. Cancer Epidemiol Biomarkers Prev 2006; 15: 1761–1764.
- 11 Edwards SM, Eeles RA. Unravelling the genetics of prostate cancer. Am J Med Genet C Semin Med Genet 2003; 129C: 65–73.
- 12 Coughlin SS, Hall IJ. A review of genetic polymorphisms and prostate cancer risk. Ann Epidemiol 2002; 12: 182–196.
- 13 Kumar-Sinha C, Chinnaiyan AM. Molecular markers to identify patients at risk for recurrence after primary treatment for prostate cancer. Urology 2003; 62: 19–35.
- 14 Schaid DJ. The complex genetic epidemiology of prostate cancer. Hum Mol Genet 2004; 13: R103–R121.
- 15 Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature 2005; 434: 843–850.
- 16 Powell SM, Zilz N, Beazer-Barclay Y, Bryan TM, Hamilton SR, Thibodeau SN, Vogelstein B, Kinzler KW. APC mutations occur early during colorectal tumorigenesis. Nature 1992; 359: 235–237.
- 17 Sparks AB, Morin PJ, Vogelstein B, Kinzler KW. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res 1998; 58: 1130–1134.
- 18 Ozaki S, Ikeda S, Ishizaki Y, Kurihara T, Tokumoto N, Iseki M, Arihiro K, Kataoka T, Okajima M, Asahara T. Alterations and correlations of the components in the Wnt signaling pathway and its target genes in breast cancer. Oncol Rep 2005; 14: 1437–1443.
- 19 Rhee C-S, Sen M, Lu D, Wu C, Leoni L, Rubin J, Corr M, Carson DA. Wnt and frizzled receptors as potential targets for immunotherapy in head and neck squamous cell carcinomas. Oncogene 2002; 21: 6598–6605.
- 20 Iwai S, Katagiri W, Kong C, Amekawa S, Nakazawa M, Yura Y. Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma. J Cancer Res Clin Oncol 2005; 131: 773–782.
- 21 Weeraratna AT, Jiang Y, Hostetter G, Rosenblatt K, Duray P, Bittner M, Trent JM. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 2002; 1: 279–288.
- 22 Chesire DR, Ewing CM, Sauvageot J, Bova GS, Isaacs WB. Detection and analysis of beta-catenin mutations in prostate cancer. Prostate 2000; 45: 323–334.
- 23 Gerstein AV, Almeida TA, Zhao G, Chess E, Shih I-M, Buhler K, Pienta K, Rubin MA, Vessella R, Papadopoulos N. APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers. Genes Chromosomes Cancer 2002; 34: 9–16.
- 24 Voeller HJ, Truica CI, Gelmann EP. Beta-catenin mutations in human prostate cancer Cancer Res 1998; 58: 2520–2523.
- 25 Yang X, Chen MW, Terry S, Vacherot F, Bemis DL, Capodice J, Kitajewski J, de la Taille A, Benson MC, Guo Y, Buttyan R. Complex regulation of human androgen receptor expression by Wnt signaling in prostate cancer cells. Oncogene 2006; 25: 3436–3444.
- 26 Masiello D, Chen SY, Xu Y, Verhoeven MC, Choi E, Hollenberg AN, Balk SP. Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells. Mol Endocrinol 2004; 18: 2388–2401.
- 27 Amir AL, Barua M, McKnight NC, Cheng S, Yuan X, Balk SP. A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4. J Biol Chem 2003; 278: 30828–33034.
- 28 Burwinkel B, Shanmugam KS, Hemminki K, Meindl A, Schmutzler RK, Sutter C, Wappenschmidt B, Kiechle M, Bartram CR, Frank B. Transcription factor 7-like 2 (TCF7L2) variant is associated with familial breast cancer risk: A case-control study. BMC Cancer 2006; 6: 268.
- 29 Cauchi S, Meyre D, Dina C, Choquet H, Samson C, Gallina S, Balkau B, Charpentier G, Pattou F, Stetsyuk V, Scharfmann R, Staels B, Fruhbeck G, Froguel P. Transcription factor TCF7L2 genetic study in the French population: Expression in human beta-cells and adipose tissue and strong association with type 2 diabetes. Diabetes 2006; 55: 2903–2908.
- 30 Damcott CM, Pollin TI, Reinhart LJ, Ott SH, Shen H, Silver KD, Mitchell BD, Shuldiner AR. Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish: Replication and evidence for a role in both insulin secretion and insulin resistance. Diabetes 2006; 55: 2654–2659.
- 31 Groves CJ, Zeggini E, Minton J, Frayling TM, Weedon MN, Rayner NW, Hitman GA, Walker M, Wiltshire S, Hattersley AT, McCarthy MI. Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. Diabetes 2006; 55: 2640–2644.
- 32 Scott LJ, Bonnycastle LL, Willer CJ, Sprau AG, Jackson AU, Narisu N, Duren WL, Chines PS, Stringham HM, Erdos MR, Valle TT, Tuomilehto J, Bergman RN, Mohlke KL, Collins FS, Boehnke M. Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample. Diabetes 2006; 55: 2649–2653.
- 33 Zhang C, Qi L, Hunter DJ, Meigs JB, Manson JE, van Dam RM, Hu FB. Variant of transcription factor 7-like 2 (TCF7L2) gene and the risk of type 2 diabetes in large cohorts of U.S. women and men. Diabetes 2006; 9: 2645–2648.
- 34 Coker AL, Sanderson M, Zheng W, Fadden MK. Diabetes mellitus and prostate cancer risk among older men: Population-based case-control study. Br J Cancer 2004; 90: 2171–2175.
- 35 Gonzalez-Perez A, Garcia Rodriguez LA. Prostate cancer risk among men with diabetes mellitus (Spain). Cancer Causes Control 2005; 16: 1055–1058.
- 36 Rodriguez C, Patel AV, Mondul AM, Jacobs EJ, Thun MJ, Calle EE. Diabetes and risk of prostate cancer in a prospective cohort of US men. Am J Epidemiol 2005; 161: 147–152.
- 37 Zhu K, Lee I-M, Sesso HD, Buring JE, Levine RS, Gaziano JM. History of diabetes mellitus and risk of prostate cancer in physicians. Am J Epidemiol 2004; 159: 978–982.
- 38 Stanford JL, Wicklund KG, McKnight B, Daling JR, Brawer MK. Vasectomy and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 1999; 8: 881–886.
- 39
Ott J.
Analysis of human genetic linkage.
3rd edition.
Baltimore: Johns Hopkins University Press
1999.
10.56021/9780801861406 Google Scholar
- 40 Breslow NE, Day NE. Statistical methods in cancer research. Volume I—The analysis of case-control studies. Lyon: IARC Scientific Publications 1980.
- 41 Dubin N, Pasternack BS. Risk assessment for case-control subgroups by polychotomous logistic regression. Am J Epidemiol 1986; 123: 1101–1117.
