Nielsen M, Franken P F, Reinards T H C M, Weiss M M, Wagner A, van der Klift H, Kloosterman S, Houwing-Duistermaat J J, Aalfs C M, Ausems M G E M, Bröcker-Vriends A H J T, Gomez Garcia E B, Hoogerbrugge N, Menko F H, Sijmons R H, Verhoef S, Kuipers E J, Morreau H, Breuning M H, Tops C M J, Wijnen J T, Vasen H F A, Fodde R, Hes F J
J Med Genet. 2005 Sep;42(9):e54. doi: 10.1136/jmg.2005.033217.
To investigate the contribution of MYH associated polyposis coli (MAP) among polyposis families in the Netherlands, and the prevalence of colonic and extracolonic manifestations in MAP patients.
170 patients with polyposis coli, who previously tested negative for APC mutations, were screened by denaturing gradient gel electrophoresis and direct sequencing to identify MYH germline mutations.
Homozygous and compound heterozygous MYH mutations were identified in 40 patients (24%). No difference was found in the percentage of biallelic mutation carriers between patients with 10-99 polyps or 100-1000 polyps (29% in both groups). Colorectal cancer was found in 26 of the 40 patients with MAP (65%) within the age range 21 to 67 years (median 45). Complete endoscopic reports were available for 16 MAP patients and revealed five cases with gastro-duodenal polyps (31%), one of whom also presented with a duodenal carcinoma. Breast cancer occurred in 18% of female MAP patients, significantly more than expected from national statistics (standardised morbidity ratio = 3.75).
Polyp numbers in MAP patients were equally associated with the attenuated and classical polyposis coli phenotypes. Two thirds of the MAP patients had colorectal cancer, 95% of whom were older than 35 years, and one third of a subset of patients had upper gastrointestinal lesions. Endoscopic screening of the whole intestine should be carried out every two years for all MAP patients, starting from age 25-30 years. The frequent occurrence of additional extraintestinal manifestations, such as breast cancer among female MAP patients, should be thoroughly investigated.
研究荷兰息肉病家族中MYH相关息肉病（MAP）的贡献，以及MAP患者结肠和结肠外表现的患病率。
对170例先前APC突变检测呈阴性的息肉病患者进行变性梯度凝胶电泳和直接测序，以鉴定MYH种系突变。
在40例患者（24%）中鉴定出纯合和复合杂合MYH突变。息肉数为10 - 99个或100 - 1000个的患者中双等位基因突变携带者的百分比无差异（两组均为29%）。40例MAP患者中有26例（65%）在21至67岁（中位年龄45岁）范围内发生了结直肠癌。16例MAP患者有完整的内镜报告，其中5例有胃十二指肠息肉（31%），其中1例还患有十二指肠癌。18%的女性MAP患者发生乳腺癌，显著高于国家统计预期（标准化发病比 = 3.75）。
MAP患者的息肉数量与attenuated型和经典型息肉病的表型同样相关。三分之二的MAP患者患有结直肠癌，其中95%年龄大于35岁，三分之一的患者亚组有上消化道病变。所有MAP患者应从25 - 30岁开始每两年进行一次全肠道内镜筛查。应深入研究女性MAP患者中乳腺癌等额外肠外表现的频繁发生情况。
