PanScan Consortium (Including:

). (2010) Evaluation of association of HNF1B variants with diverse cancers : collaborative analysis of data from 19 genome-wide association studies. PLoS One, Vol.5 (No.5). e10858. ISSN 1932-6203

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Abstract

Background Genome-wide association studies have found type 2 diabetes-associated variants in the HNF1B gene to exhibit reciprocal associations with prostate cancer risk. We aimed to identify whether these variants may have an effect on cancer risk in general versus a specific effect on prostate cancer only. Methodology/Principal Findings In a collaborative analysis, we collected data from GWAS of cancer phenotypes for the frequently reported variants of HNF1B, rs4430796 and rs7501939, which are in linkage disequilibrium (r2 = 0.76, HapMap CEU). Overall, the analysis included 16 datasets on rs4430796 with 19,640 cancer cases and 21,929 controls; and 21 datasets on rs7501939 with 26,923 cases and 49,085 controls. Malignancies other than prostate cancer included colorectal, breast, lung and pancreatic cancers, and melanoma. Meta-analysis showed large between-dataset heterogeneity that was driven by different effects in prostate cancer and other cancers. The per-T2D-risk-allele odds ratios (95% confidence intervals) for rs4430796 were 0.79 (0.76, 0.83)] per G allele for prostate cancer (p<10−15 for both); and 1.03 (0.99, 1.07) for all other cancers. Similarly for rs7501939 the per-T2D-risk-allele odds ratios (95% confidence intervals) were 0.80 (0.77, 0.83) per T allele for prostate cancer (p<10−15 for both); and 1.00 (0.97, 1.04) for all other cancers. No malignancy other than prostate cancer had a nominally statistically significant association. Conclusions/Significance The examined HNF1B variants have a highly specific effect on prostate cancer risk with no apparent association with any of the other studied cancer types.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Prostate -- Cancer, Non-insulin-dependent diabetes, Cancer -- Susceptibility
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Date:	28 May 2010
Volume:	Vol.5
Number:	No.5
Number of Pages:	8
Page Range:	e10858
Identification Number:	10.1371/journal.pone.0010858
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	National Institutes of Health (U.S.) (NIH), Wellcome Trust (London, England), National Health and Medical Research Council (Australia) (NHMRC), Cancerfonden, Sweden. Vetenskapsrådet [Research Council], Cancer Research UK (CRUK), National Cancer Research Institute (NCRI), Medical Research Council (Great Britain) (MRC)
Grant number:	UL1 RR025752 (NIH), R01-CA88363 (NIH), WT075491/Z/04 (WT), WT088885/Z/09/Z (WT), C5047/A8385 (CRUK), C5047/A7357 (CRUK)
References:	1. Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, et al. (2006) Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med 166: 1871–1877. 2. Stattin P, Bjor O, Ferrari P, Lukanova A, Lenner P, et al. (2007) Prospective study of hyperglycemia and cancer risk. Diabetes Care 30: 561–567. 3. Rousseau MC, Parent ME, Pollak MN, Siemiatycki J (2006) Diabetes mellitus and cancer risk in a population-based case-control study among men from Montreal, Canada. Int J Cancer 118: 2105–2109. 4. Kasper JS, Giovannucci E (2006) A meta-analysis of diabetes mellitus and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 15: 2056–2062. 5. Gong Z, Neuhouser ML, Goodman PJ, Albanes D, Chi C, et al. (2006) Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev 15: 1977–1983. 6. Calton BA, Chang SC, Wright ME, Kipnis V, Lawson K, et al. (2007) History of diabetes mellitus and subsequent prostate cancer risk in the NIH-AARP Diet and Health Study. Cancer Causes Control 18: 493–503. 7. Will JC, Vinicor F, Calle EE (1999) Is diabetes mellitus associated with prostate cancer incidence and survival? Epidemiology 10: 313–318. 8. Manolio TA, Brooks LD, Collins FS (2008) A HapMap harvest of insights into the genetics of common disease. J Clin Invest 118: 1590–1605. 9. Gudmundsson J, Sulem P, Steinthorsdottir V, Bergthorsson JT, Thorleifsson G, et al. (2007) Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet 39: 977–983. 10. Sun J, Zheng SL, Wiklund F, Isaacs SD, Purcell LD, et al. (2008) Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12. Nat Genet 40: 1153–1155. 11. Thomas G, Jacobs KB, Yeager M, Kraft P, Wacholder S, et al. (2008) Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet. 12. Winckler W, Weedon MN, Graham RR, McCarroll SA, Purcell S, et al. (2007) Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes. Diabetes 56: 685–693. 13. Horikawa Y, Iwasaki N, Hara M, Furuta H, Hinokio Y, et al. (1997) Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet 17: 384–385. 14. Tenesa A, Farrington SM, Prendergast JG, Porteous ME, Walker M, et al. (2008) Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nat Genet 40: 631–637. 15. Gold B, Kirchhoff T, Stefanov S, Lautenberger J, Viale A, et al. (2008) Genomewide association study provides evidence for a breast cancer risk locus at 6q22.33. Proc Natl Acad Sci U S A 105: 4340–4345. 16. Maris JM, Mosse YP, Bradfield JP, Hou C, Monni S, et al. (2008) Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. N Engl J Med 358: 2585–2593. 17. Cust AE, Schmid H, Maskiell JA, Jetann J, Ferguson M, et al. (2009) Populationbased, case-control-family design to investigate genetic and environmental influences on melanoma risk: Australian Melanoma Family Study. Am J Epidemiol 170: 1541–1554. 18. Eeles RA, Kote-Jarai Z, Giles GG, Olama AA, Guy M, et al. (2008) Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet 40: 316–321. 19. Petersen GM, Amundadottir L, Fuchs CS, Kraft P, Stolzenberg-Solomon RZ, et al. (2010) A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet 42: 224–228. 20. Brennan P, McKay J, Moore L, Zaridze D, Mukeria A, et al. (2007) Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: case control study. Hum Mol Genet 16: 1794–1801. 21. Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, et al. (2008) A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452: 633–637. 22. Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, et al. (2008) Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 40: 616–622. 23. Zanke BW, Greenwood CM, Rangrej J, Kustra R, Tenesa A, et al. (2007) Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet 39: 989–994. 24. Brown KM, Macgregor S, Montgomery GW, Craig DW, Zhao ZZ, et al. (2008) Common sequence variants on 20q11.22 confer melanoma susceptibility. Nat Genet 40: 838–840. 25. Yeager M, Orr N, Hayes RB, Jacobs KB, Kraft P, et al. (2007) Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet 39: 645–649. 26. Duggan D, Zheng SL, Knowlton M, Benitez D, Dimitrov L, et al. (2007) Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP. J Natl Cancer Inst 99: 1836–1844. 27. Tomlinson IP, Webb E, Carvajal-Carmona L, Broderick P, Howarth K, et al. (2008) A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat Genet 40: 623–630. 28. Stacey SN, Manolescu A, Sulem P, Thorlacius S, Gudjonsson SA, et al. (2008) Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 40: 703–706. 29. Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, et al. (2009) Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41: 221–227. 30. Thorgeirsson TE, Geller F, Sulem P, Rafnar T, Wiste A, et al. (2008) A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452: 638–642. 31. Gudmundsson J, Sulem P, Manolescu A, Amundadottir LT, Gudbjartsson D, et al. (2007) Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet 39: 631–637. 32. Gudmundsson J, Sulem P, Rafnar T, Bergthorsson JT, Manolescu A, et al. (2008) Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer. Nat Genet. 33. Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, et al. (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447: 1087–1093. 34. http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000007. v9.p4. 35. Edghill EL, Bingham C, Ellard S, Hattersley AT (2006) Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet 43: 84–90. 36. Rebouissou S, Vasiliu V, Thomas C, Bellanne-Chantelot C, Bui H, et al. (2005) Germline hepatocyte nuclear factor 1alpha and 1beta mutations in renal cell carcinomas. Hum Mol Genet 14: 603–614. 37. Reber M, Cereghini S (2001) Variant hepatocyte nuclear factor 1 expression in the mouse genital tract. Mech Dev 100: 75–78. 38. Coffinier C, Barra J, Babinet C, Yaniv M (1999) Expression of the vHNF1/ HNF1beta homeoprotein gene during mouse organogenesis. Mech Dev 89: 211–213. 39. Ioannidis JP, Thomas G, Daly MJ (2009) Validating, augmenting and refining genome-wide association signals. Nat Rev Genet 10: 318–329. 40. Yamada H, Penney KL, Takahashi H, Katoh T, Yamano Y, et al. (2009) Replication of prostate cancer risk loci in a Japanese case-control association study. J Natl Cancer Inst 101: 1330–1336. 41. Levin AM, Machiela MJ, Zuhlke KA, Ray AM, Cooney KA, et al. (2008) Chromosome 17q12 variants contribute to risk of early-onset prostate cancer. Cancer Res 68: 6492–6495. 42. Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, et al. (2008) Metaanalysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 40: 638–645. 43. Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, et al. (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316: 1336–1341. 44. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, et al. (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A 106: 9362–9367. 45. Kavvoura FK, Ioannidis JP (2008) Methods for meta-analysis in genetic association studies: a review of their potential and pitfalls. Hum Genet 123: 1–14. 46. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. Bmj 327: 557–560. 47. Ioannidis JP, Patsopoulos NA, Evangelou E (2007) Uncertainty in heterogeneity estimates in meta-analyses. Bmj 335: 914–916. 48. Petersen GM, Amundadottir L, Fuchs CS, Kraft P, Stolzenberg-Solomon RZ, et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet.
URI:	http://wrap.warwick.ac.uk/id/eprint/3278

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