Countermatching is essentially a matched variant of the two-phase design. Here one or more controls are selected for each case on the basis of exposure so that each matched set contains the same number of exposed individuals. Another study of CBC in relation to RT and DNA damage repair genes49 counter-matched each CBC case to two controls with unilateral breast cancer, such that each matched set contained two RT+ subjects. Radiation doses to each quadrant of the contralateral breast were then estimated and DNA was obtained for genotyping candidate DNA repair genes and for a GWA scan. Langholz50 has demonstrated the considerable gains in power that can be obtained, both for main effects and for interactions. In particular, for G×E interactions Andrieu et al.51 showed that a 1:1:1:1 design counter-matched on surrogates for both exposure and genotype was more powerful than conventional 1:3 nested case-control or 1:3 or 2:2 designs counter-matched on just one of these factors.
