title: Earlier age of onset of BRCA mutation-related cancers in subsequent generations.
abstract: BACKGROUND
  Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages. In this study, the authors assessed age at diagnosis in 2 generations of families with known mutations to investigate for earlier onset in subsequent generations.
  
  
  METHODS
  Of the 132 BRCA-positive women with breast cancer who participated in a high-risk protocol at The University of Texas MD Anderson Cancer Center (Gen 2), 106 women could be paired with a family member in the previous generation (Gen 1) who was diagnosed with a BRCA-related cancer (either breast cancer or ovarian cancer). Age at diagnosis, location of the mutation, and year of birth were recorded. A previously published parametric anticipation model was applied in these genetically predisposed families.
  
  
  RESULTS
  The median age of cancer diagnosis was 42 years (range, 28-55 years) in Gen 2 and 48 years (range, 30-72 years) in Gen 1 (P < .001). [corrected]. In the parametric model, the estimated change in the expected age at onset for the entire cohort was 7.9 years (P < .0001). Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.
  
  
  CONCLUSIONS
  Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations. The authors concluded that patients who are younger at the onset of BRCA-related cancers should continue to be tracked to offer appropriate screening modalities at appropriate ages.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA. jlitton@mdanderson.org
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Litton
authors.forename: Kaylene
authors.initials: K
authors.lastname: Ready
authors.forename: Huiqin
authors.initials: H
authors.lastname: Chen
authors.forename: Angelica
authors.initials: A
authors.lastname: Gutierrez-Barrera
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Etzel
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: Huong
authors.initials: H
authors.lastname: Le-Petross
authors.forename: Karen
authors.initials: K
authors.lastname: Lu
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Banu K
authors.initials: BK
authors.lastname: Arun
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics; D012306:Risk