title: Novel polymorphisms in caspase-8 are associated with breast cancer risk in the California Teachers Study.
abstract: BACKGROUND
  The ability of tamoxifen and raloxifene to decrease breast cancer risk varies among different breast cancer subtypes. It is important to determine one's subtype-specific breast cancer risk when considering chemoprevention. A number of single nucleotide polymorphisms (SNPs), including one in caspase-8 (CASP8), have been previously associated with risk of developing breast cancer. Because caspase-8 is an important protein involved in receptor-mediated apoptosis whose activity is affected by estrogen, we hypothesized that additional SNPs in CASP8 could be associated with breast cancer risk, perhaps in a subtype-specific manner.
  
  
  METHODS
  Twelve tagging SNPs of CASP8 were analyzed in a nested case control study (1,353 cases and 1,384 controls) of non-Hispanic white women participating in the California Teachers Study. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each SNP using all, estrogen receptor (ER)-positive, ER-negative, human epidermal growth factor receptor 2 (HER2)-positive, and HER2-negative breast cancers as separate outcomes.
  
  
  RESULTS
  Several SNPs were associated with all, ER-positive, and HER2-positive breast cancers; however, after correcting for multiple comparisons (i.e., p < 0.0008), only rs2293554 was statistically significantly associated with HER2-positive breast cancer (OR = 1.98, 95% CI 1.34-2.92, uncorrected p = 0.0005).
  
  
  CONCLUSIONS
  While our results for CASP8 SNPs should be validated in other cohorts with subtype-specific information, we conclude that some SNPs in CASP8 are associated with subtype-specific breast cancer risk. This study contributes to our understanding of CASP8 SNPs and breast cancer risk by subtype.
authors.affiliation: Department of Epidemiology, University of California, Irvine, School of Medicine, 224 Irvine Hall, Irvine, CA, 92697, USA. hlpark@uci.edu.
authors.forename: Hannah Lui
authors.initials: HL
authors.lastname: Park
authors.affiliation: Department of Epidemiology, University of California, Irvine, School of Medicine, 224 Irvine Hall, Irvine, CA, 92697, USA. aziogas@uci.edu.
authors.forename: Argyrios
authors.initials: A
authors.lastname: Ziogas
authors.affiliation: Department of Epidemiology, University of California, Irvine, School of Medicine, 224 Irvine Hall, Irvine, CA, 92697, USA. jjchang@uci.edu.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Epidemiology, University of California, Irvine, School of Medicine, 224 Irvine Hall, Irvine, CA, 92697, USA. desaib13@gmail.com.
authors.forename: Bhumi
authors.initials: B
authors.lastname: Desai
authors.affiliation: Department of Epidemiology, University of California, Irvine, School of Medicine, 224 Irvine Hall, Irvine, CA, 92697, USA. leona.bessonova@live.com.
authors.forename: Leona
authors.initials: L
authors.lastname: Bessonova
authors.affiliation: Department of Epidemiology, University of California, Irvine, School of Medicine, 224 Irvine Hall, Irvine, CA, 92697, USA. cgarner@uci.edu.
authors.forename: Chad
authors.initials: C
authors.lastname: Garner
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, USA. Eunjung.Lee@med.usc.edu.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, 91010, USA. sneuhausen@coh.org.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, 91010, USA. sowang@coh.org.
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, 91010, USA. HMa@coh.org.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Ma
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, 91010, USA. jclague@coh.org.
authors.forename: Jessica
authors.initials: J
authors.lastname: Clague
authors.affiliation: Cancer Prevention Institute of California, Berkeley, CA, 94704, USA. Peggy.Reynolds@cpic.org.
authors.forename: Peggy
authors.initials: P
authors.lastname: Reynolds
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, 91010, USA. jlacey@coh.org.
authors.forename: James V
authors.initials: JV
authors.lastname: Lacey
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, 91010, USA. LBernstein@coh.org.
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.affiliation: Department of Epidemiology, University of California, Irvine, School of Medicine, 224 Irvine Hall, Irvine, CA, 92697, USA. hantoncu@uci.edu.
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002140:California; D053181:Caspase 8 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D012307:Risk Factors
chemical_list: D053181:Caspase 8; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human