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Genetic risk variants associated with in situ breast cancer.

About this Publication
Title
Genetic risk variants associated with in situ breast cancer.
Pubmed ID
26070784 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Breast Cancer Res. 2015 Jun; Volume 17: Pages 82
Authors
Campa D, Barrdahl M, Gaudet MM, Black A, Chanock SJ, Diver WR, Gapstur SM, Haiman C, Hankinson S, Hazra A, Henderson B, Hoover RN, Hunter DJ, Joshi AD, Kraft P, Le Marchand L, Lindström S, Willett W, Travis RC, Amiano P, ...show more Siddiq A, Trichopoulos D, Sund M, Tjønneland A, Weiderpass E, Peeters PH, Panico S, Dossus L, Ziegler RG, Canzian F, Kaaks R
Affiliations
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. daniele.campa@unipi.it.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. m.barrdahl@dkfz.de.
  • Epidemiology Research Program, American Cancer Society, 250 Williams Street NW, Atlanta, GA, 30303, USA. Mia.gaudet@cancer.org.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA. blacka@mail.nih.gov.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA. chanocks@mail.nih.gov.
  • Epidemiology Research Program, American Cancer Society, 250 Williams Street NW, Atlanta, GA, 30303, USA. Ryan.diver@cancer.org.
  • Epidemiology Research Program, American Cancer Society, 250 Williams Street NW, Atlanta, GA, 30303, USA. Susan.gapstur@cancer.org.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1975 Zonal Avenue, Los Angeles, CA, 90033, USA. Christopher.haiman@med.usc.edu.
  • Department of Epidemiology, University of Massachusetts-Amherst School of Public Health and Health Sciences, 715 North Pleasant Street, Amherst, MA, 01003, USA. shankinson@schoolph.umass.edu.
  • Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. ahazra@hsph.harvard.edu.
...show more
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1975 Zonal Avenue, Los Angeles, CA, 90033, USA. bhender@usc.edu.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA. hooverr@exchange.nih.gov.
  • Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. dhunter@hsph.harvard.edu.
  • Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. ajoshi@hsph.harvard.edu.
  • Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. pkraft@hsph.harvard.edu.
  • Cancer Research Center of Hawaii, University of Hawaii, 701 Ilalo Street, Honolulu, HI, 96813, USA. loic@crch.hawaii.edu.
  • Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. slindstr@hsph.harvard.edu.
  • Department of Nutrition, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA, 02115, USA. wwillett@hsph.harvard.edu.
  • Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Roosevelt Drive, Oxford, OX3 7LF, UK. ruth.travis@ceu.ox.ac.uk.
  • Public Health Division of Gipuzkoa, BIODonostia Research Institute, Basque Health Department, Avenida Navarra 4, 20013, San Sebastian, Spain. epicss-san@ej-gv.es.
  • School of Public Health, Imperial College, Norfolk Place, London, W2 1PG, UK. a.siddiq@imperial.ac.uk.
  • Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. dtrichop@hsph.harvard.edu.
  • Department of Surgical and Perioperative Sciences, Umeå University, 901 87, Umeå, Sweden. malin.sund@umu.se.
  • Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark. annet@cancer.dk.
  • Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Hansine Hansens veg 18, 9037, Tromsø, Norway. Elisabete.Weiderpass.Vainio@ki.se.
  • Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands. P.H.M.Peeters@umcutrecht.nl.
  • Dipartimento di Medicina Clinica e Chirurgia Federico II University, via Sergio Pansini 5, Naples, 80131, Italy. spanico@unina.it.
  • Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, 16 avenue Paul Vaillant Couturier, 94805, Villejuif, France. Laure.DOSSUS@lyon.unicancer.fr.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA. zieglerr@mail.nih.gov.
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. f.canzian@dkfz.de.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. r.kaaks@dkfz.de.
Abstract

INTRODUCTION: Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS.

METHODS: To evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile.

RESULTS: We found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582, TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (P value adjusted for multiple comparisons <0.0016). Comparing invasive BC and BCIS, the largest difference was for CDKN2BAS-rs1011970, which showed a positive association with BCIS (OR = 1.24, 95 % CI: 1.11-1.38, P = 1.27 x 10(-4)) and no association with invasive BC (OR = 1.03, 95 % CI: 0.99-1.07, P = 0.06), with a P value for case-case comparison of 0.006. Subgroup analyses investigating associations with ductal carcinoma in situ (DCIS) found similar associations, albeit less significant (OR = 1.25, 95 % CI: 1.09-1.42, P = 1.07 x 10(-3)). Additional risk analyses showed significant associations with invasive disease at the 0.05 level for 28 of the alleles and the OR estimates were consistent with those reported by other studies.

CONCLUSIONS: Our study adds to the knowledge that several of the known BC susceptibility loci are risk factors for both BCIS and invasive BC, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific BCIS susceptibility locus.

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