Hemminki A, Höglund P, Pukkala E, Salovaara R, Järvinen H, Norio R, Aaltonen L A
Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
Oncogene. 1998 Feb 5;16(5):681-4. doi: 10.1038/sj.onc.1201538.
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.
最近一项研究显示，腺瘤下调基因（DRA）的种系突变可能是隐性肠道吸收缺陷即先天性氯化物腹泻的病因。这一发现与之前的研究结果一致，之前的研究表明DRA编码一种对硫酸盐和草酸盐不依赖钠的转运蛋白。尽管DRA最初被报道为一种候选肿瘤抑制基因，但这些研究对DRA在癌症中的相关性提出了质疑。为了评估对DRA在肿瘤发生中作用的进一步研究是否仍有意义，我们调查了携带DRA种系突变的个体是否患肠癌的风险更高。在芬兰癌症登记处查询了36个芬兰先天性氯化物腹泻家族的229名成员（44名纯合患者、70名杂合父母以及115名有50%概率携带DRA突变的祖父母）的癌症状况，发现患肠癌的风险略有升高（标准化发病率3.4，95%置信区间1.4 - 7.0，P < 0.05）。虽然这一结果并未明确表明DRA突变携带者患肠癌的风险增加，但它应该促使进一步的研究来确定DRA在癌症中的可能作用。
