Reproductive factors and familial predisposition for XXXX by age 50 years. A case-control-family study for assessing main effects and possible gene-environment interaction.

@entity1 @entity0 @entity5344
BACKGROUND: The effect of environmental/lifestyle factors on @entity0 risk may be modified by genetic predisposition. METHODS: In a population-based case-control-family study performed in Germany including 706 cases by age 50 years, 1381 population, and 252 sister controls, we investigated main effects for environmental/lifestyle factors and genetic susceptibility and gene-environment interaction (G x E). Different surrogate measures for genetic predisposition using pedigree information were used: first-degree family history of @entity5344 ; and gene carrier probability using a genetic model based on rare dominant genes. Possible G x E interaction was studied by (1) logistic regression using cases and population controls including an interaction term; (2) comparing results using sister controls and population controls; (3) case-only analysis with logistic regression and (4) a mixture logistic model. RESULTS: Familial predisposition showed the strongest main effect and the estimated gene carrier probability gave the best fit. High parity and longer duration of breastfeeding reduced @entity0 risk significantly, a history of abortions increased risk and age at menarche showed no significant effect. We found significant G x E interaction between parity and genetic susceptibility using different surrogate measures. In @entity1 most likely to have a high genetic susceptibility, high parity was less protective. Later age at menarche was protective in @entity1 with a positive family history. No evidence for G x E interaction was found for breastfeeding and abortion. CONCLUSIONS: These findings corroborate results from other studies and provide further evidence that the magnitude of protection from parity is reduced in @entity1 most likely to have a genetic risk in spite of the limitations of using surrogate genetic measures.
