INTESTINAL CANCER IN PATIENTS WITH A GERMLINE MUTATION IN THE DOWN-REGULATED IN ADENOMA (DRA) GENE

A recent study has revealed that germline mutations of the down-regula ted in adenoma (DRA) gene are a likely cause of a recessive intestinal absorption defect, congenital chloride diarrhea, This finding was in accordance with previous works showing that DRA encodes a sodium indep endent transporter for sulfate and oxalate, Although DRA was originall y reported as a candidate tumor suppressor, these studies have questio ned the relevance of DRA in cancer. To evaluate whether further studie s on the role of DRA in tumorigenesis are still of interest, we examin ed whether individuals carrying germline DRA mutations have an excess of intestinal cancer, Cancer status of 229 members of 36 Finnish conge nital chloride diarrhea families (44 homozygous patients, 70 heterozyg ous parents, and 115 grandparents at 50% risk of being a DRA mutation carrier) was checked at the Finnish Cancer Registry and the risk of in testinal cancer was found slightly elevated (standardized incidence ra tio 3.4, 95% confidence interval 1.4-7.0, P<0.05). While this result d oes not unambiguously demonstrate an increased intestinal cancer risk in DRA mutation carriers, it should promote further studies to determi ne the possible role of DRA in cancer.