Estimation of the gene-environment interaction in breast cancer patients

ABSTRACT

There is growing interest in assessing gene-environment interaction in the course of case-control studies. Difficulties related to the sampling of controls have led to the development of a range of non-traditional methods that do not require controls for estimating gene-environment interaction. One of these new modalities is the case-only approach, in which the assessment of gene-environment interaction is based on information from the cases only. The present article describes the application of this approach to data from breast cancer patients and compares its efficacy with that of a traditional case-control analysis. We used age at first pregnancy, number of live birth, menopause and the total number of post-menopausal years as the [environment] factors and family history of breast cancer as the [gene] factor. We computed standard errors, 95% confidence intervals and [-2 log likelihood] to compare efficiency between case-control and case-only analyses. We observed significant interaction between menopause and family history of breast cancer by both methods [OR=4.32 CI 1.10-16.90 for case-control analysis and OR=3.40 CI 1.17-9.87 for case-only analysis]. There was also a significant interaction effect between total years after menopause and family history of breast cancer [OR=1.07 CI 0.98-1.16 in case-control analysis and OR=1.07 CI 1.01-1.12 in case-only analysis]. The case-only approach yielded narrower confidence intervals for the odds ratio, and the [-2 log likelihood] values computed by this method were correspondingly smaller. Comparison of confidence intervals and [-2 log likelihood] values shows that the estimation of gene-environment interaction in breast cancer would be more efficient with the case-only approach than with the traditional case-control analysis: