In comparison with the mismatch repair genes MLH1 and MSH2, the genes MSH6 and PMS2 are relatively understudied with respect to cancer risk. However, some recent large studies of data combined from several sources, using analytic methods that appropriately condition on the varying methods of ascertainment, are producing reasonably precise estimates, which can be used for risk estimation in patients. To identify modifiers for risk in such carriers, a goal for epidemiologists to improve the health of carriers, such collaborative studies need to continue and expand to include additional mutation carriers in which lifestyle factors and DNA samples are available for analysis.