Although hMSH2 has three NR recognition motifs (LXXLL, NR box), these motifs have no significant role in the binding of ER α and ER β. Given that hMSH2 may promote gene regulation with ERs, and that the mutations in hMSH2 may lead to an altered ER α-dependent gene regulation and an altered tumorigenesis in oestrogen-dependent cancers (presumably through the modulation of ER-mediated oestrogen signalling), the interaction between ER α/β and hMSH2 may partially account for the relationship between HNPCC and oestrogen-dependent extracolonic tumours such as endometrial cancer. The gene discussed is MSH2; the disease is neoplasm.