Inference about Causation from Examination of Familial Confounding: Application to Longitudinal Twin Data on Mammographic Density Measures that Predict Breast Cancer Risk
AuthorStone, Jennifer; Dite, Gillian S.; Giles, Graham G.; Cawson, Jennifer; English, Dallas R.; Hopper, John L.
Source TitleCANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
PublisherAMER ASSOC CANCER RESEARCH
University of Melbourne Author/sStone, Jennifer; Dite, Gillian; Giles, Graham; English, Dallas; Hopper, John
AffiliationMelbourne School of Population and Global Health
Document TypeJournal Article
Access StatusThis item is currently not available from this repository
NHMRC Grant codeNHMRC/300048
Fulltext embargoed for: 12 months post date of publication
Background: Mammographic density is a strong risk factor for breast cancer. It is unknown whether there are different causes of variation in mammographic density at different ages.Methods: Mammograms and questionnaires were obtained on average 8 years apart from 327 Australian female twin pairs (204 monozygous and 123 dizygous). Mammographic dense area and percentage dense area were measured using a computer-assisted method. The correlational structure of the longitudinal twin data was estimated under a multivariate normal model using FISHER. Inference about causation from examination of familial confounding was made by regressing each twin's recent mammographic density measure against one or both of her and her co-twin's past measures.Results: For square root dense area and percentage dense area (age- and body mass index adjusted), the correlations over time within twins were 0.86 and 0.82, and the cross-twin correlations were 0.71 and 0.65 for monozygous pairs and 0.25 and 0.20 for dizygous pairs, respectively. As a predictor of a twin's recent dense area, the regression coefficient (SE) for the co-twin's past dense area reduced after adjusting for her own past measure from 0.84 (0.03) to 0.09 (0.03) for monozygous pairs and from 0.63 (0.04) to 0.04 (0.03) for dizygous pairs. Corresponding estimates for percentage dense area were 0.73 (0.04), 0.10 (0.03), 0.42 (0.05), and 0.03 (0.03).Conclusion: Mammographic density measures are highly correlated over time and the familial/genetic components of their variation are established before mid-life.Impact: Mammographic density of young women could provide a means for breast cancer control. Cancer Epidemiol Biomarkers Prev; 21(7); 1149-55.
KeywordsTISSUE; WOMEN; HERITABILITY; DISEASE; MODELS; TISSUE; WOMEN; HERITABILITY; DISEASE; MODELS
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