Future studies are needed to confirm these results in mutation carriers studied with digital mammograms.
Besides expanding our study beyond women with BRCA1/2 mutation carriers, our study differs from prior cost-effectiveness analyses of MRI in which we include CBE as a part of the screening programmes under examination since CBE is commonly used in combination with mammography in screening practice.
In contrast to previous studies that focused on BRCA1/2 mutation carriers, our study focuses on a more general high-risk population of patients with a 25% or greater lifetime risk of developing breast cancer, which makes our study more applicable to provide screening recommendations to the general high-risk population.
The UK MARIBS study was another large multicentre MRI screening study of 649 high-risk women, including 120 BRCA mutation carriers (MARIBS study group, 2005).
A global set of weights was computed because the number of mutation carriers by study was too small to compute reliable study-specific weights.
For BRCA2 mutation carriers the study reported an increase in PrCa RR of 4.65 (95% CI 3.48 6.22) rising to 7.33 (95% CI 4.66 11.52) for men <65 years (The Breast Cancer Linkage Consortium, 1999).
Moreover, the Northern extension of the area where malaria was present in the past is not well known, and thus the question of the relevance of determining the ethnic origin of the mutation carriers to study the relationship between malaria and β-globin could be raised.
Since one of the main aims of the study was to analyse cancer incidence in BRCA1 and BRCA2 noncarriers, we were not willing to include a known mutation carrier in that study group even if the detection of this case was not strictly population based.
This is, to our knowledge, the first work where the ethnic origin of mutation carriers is studied using ancestry-informative markers, and we hope it could open up the way to other similar studies that may collectively help resolve the question of the relationship between malaria and β-globin.
Our study adds to the existing RTA literature [ 19, 20] by analyzing the largest number of mutation carriers yet studied in this manner, and our findings indicate that computer-extracted mammographic features provide some additional information for identifying women likely to carry BRCA1/ 2 mutations.
