title: Additive interactions between susceptibility single-nucleotide polymorphisms identified in genome-wide association studies and breast cancer risk factors in the Breast and Prostate Cancer Cohort Consortium.
abstract: Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 × 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Joshi
authors.forename: Sara
authors.initials: S
authors.lastname: Lindström
authors.forename: Anika
authors.initials: A
authors.lastname: Hüsing
authors.forename: Myrto
authors.initials: M
authors.lastname: Barrdahl
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: VanderWeele
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Laura
authors.initials: L
authors.lastname: Baglietto
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Diver
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Fredrick
authors.initials: F
authors.lastname: Schumacher
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.forename: Shumin
authors.initials: S
authors.lastname: Zhang
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
mesh_terms: D000483:Alleles; D001315:Australia; D014408:Biomarkers, Tumor / Q000097:blood*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000097:blood*; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D051135:Rad51 Recombinase / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C413002:RAD51B protein, human; C495153:RAD51 protein, human; D051135:Rad51 Recombinase
keywords: additive interactions; breast cancer; genome-wide association studies; single-nucleotide polymorphisms