Abstract
A recent study has revealed that germline mutations of the down-regulated 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 independent transporter for sulfate and oxalate. Although DRA was originally reported as a candidate tumor suppressor, these studies have questioned the relevance of DRA in cancer. To evaluate whether further studies on the role of DRA in tumorigenesis are still of interest, we examined whether individuals carrying germline DRA mutations have an excess of intestinal cancer. Cancer status of 229 members of 36 Finnish congenital chloride diarrhea families (44 homozygous patients, 70 heterozygous parents, and 115 grandparents at 50% risk of being a DRA mutation carrier) was checked at the Finnish Cancer Registry and the risk of intestinal cancer was found slightly elevated (standardized incidence ratio 3.4, 95% confidence interval 1.4 – 7.0, P<0.05). While this result does not unambiguously demonstrate an increased intestinal cancer risk in DRA mutation carriers, it should promote further studies to determine the possible role of DRA in cancer.
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Hemminki, A., Höglund, P., Pukkala, E. et al. Intestinal cancer in patients with a germline mutation in the down-regulated in adenoma (DRA) gene. Oncogene 16, 681–684 (1998). https://doi.org/10.1038/sj.onc.1201538
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DOI: https://doi.org/10.1038/sj.onc.1201538