MLH1 and obesity due to melanocortin 4 receptor deficiency: The association we observed with MLH1 and PMS2 mutations is consistent with obesity affecting CRC risk by inducing a second hit in the remaining wild-type allele of MLH1 or PMS2. It is also consistent with obesity being a tumour promoter that is more relevant to tumours induced by MMR defects due to mutations in the MutLα heterodimer.