title: Breast Cancer Risk From Modifiable and Nonmodifiable Risk Factors Among White Women in the United States.
abstract: OBJECTIVE
  An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention.
  
  
  OBJECTIVE
  To evaluate combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors.
  
  
  METHODS
  Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for the population of white women in the United States after adjustment for competing cause of mortality.
  
  
  METHODS
  Single nucleotide polymorphisms, family history, anthropometric factors, menstrual and/or reproductive factors, and lifestyle factors.
  
  
  METHODS
  Degree of stratification of absolute risk owing to nonmodifiable (SNPs, family history, height, and some components of menstrual and/or reproductive history) and modifiable factors (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], menopausal hormone therapy [MHT], alcohol, and smoking).
  
  
  RESULTS
  The average absolute risk for a 30-year-old white woman in the United States developing invasive breast cancer by age 80 years is 11.3%. A model that includes all risk factors provided a range of average absolute risk from 4.4% to 23.5% for women in the bottom and top deciles of the risk distribution, respectively. For women who were at the lowest and highest deciles of nonmodifiable risks, the 5th and 95th percentile range of the risk distribution associated with 4 modifiable factors was 2.9% to 5.0% and 15.5% to 25.0%, respectively. For women in the highest decile of risk owing to nonmodifiable factors, those who had low BMI, did not drink or smoke, and did not use MHT had risks comparable to an average woman in the general population.
  
  
  CONCLUSIONS
  This model for absolute risk of breast cancer including SNPs can provide stratification for the population of white women in the United States. The model can also identify subsets of the population at an elevated risk that would benefit most from risk-reduction strategies based on altering modifiable factors. The effectiveness of this model for individual risk communication needs further investigation.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Paige
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authors.lastname: Maas
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Myrto
authors.initials: M
authors.lastname: Barrdahl
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Joshi
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington5School of Public Health, University of Wisconsin-Milwaukee, Milwaukee.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Auer
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta Georgia.
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia8Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: William F
authors.initials: WF
authors.lastname: Anderson
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: David
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authors.lastname: Check
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Subham
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authors.lastname: Chattopadhyay
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia8Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
authors.forename: Laura
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authors.lastname: Baglietto
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: INSERM U1052 - Cancer Research Center of Lyon, Centre Léon Bérard, Lyon, France12Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, England.
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Gail
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Graubard
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst14Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC.
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.affiliation: Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu.
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.affiliation: University of Hawaii Cancer Center, Honolulu.
authors.forename: Loic
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authors.lastname: Le Marchand
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Sara
authors.initials: S
authors.lastname: Lindström
authors.affiliation: Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.affiliation: Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain22CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Sanchez
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Australia.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.affiliation: Cancer Registry and Histopathology Unit, "Civic- M.P.Arezzo" Hospital, ASP Ragusa, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts26Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: VanderWeele
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Shumin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Federico
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authors.lastname: Canzian
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta Georgia.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia8Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia29Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington30University of Washington, School of Public Health and Community Medicine, Seattle.
authors.forename: Ross L
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authors.lastname: Prentice
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland31Breakthrough Breast Cancer Research Centre, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, England.
authors.forename: Montse
authors.initials: M
authors.lastname: Garcia-Closas
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland32Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland33Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Nilanjan
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authors.lastname: Chatterjee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D040242:Risk Reduction Behavior; D014481:United States / Q000453:epidemiology; D044465:White People