title: Risks for familial and contralateral breast cancer interact multiplicatively and cause a high risk.
abstract: The reasons for the high risk of contralateral breast cancer are not understood, although polygenic mechanisms have been suggested to be involved. The nationwide Swedish Family-Cancer Database was used to examine the interaction of the risks for contralateral and familial cancer. Relative risks were separately determined for contralateral and familial breast cancers, and these were tested for additive and multiplicative interactions. The Database contained information on 102,176 first breast cancers. Familial risk for breast cancer was 1.76 and the risk for contralateral breast cancer was 3.40, or 5.80 when extrapolated to two breasts. When women had a family history, the risk for contralateral breast cancer was remarkably high, 5.48, or 9.96 when the risk was extrapolated to two breasts, almost identical with 10.21, which was predicted by the multiplicative model. Although the data do not rule out polygenic mechanisms, they suggest that epigenetic imprinting events may be involved for the contralateral breast cancer.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany. k.hemminki@dkfz.de
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Jianguang
authors.initials: J
authors.lastname: Ji
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000235:genetics; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology