Guillem José G, Rapaport Beth S, Kirchhoff Tomas, Kolachana Prema, Nafa Khedoudja, Glogowski Emily, Finch Rob, Huang Helen, Foulkes William D, Markowitz Arnold, Ellis Nathan A, Offit Kenneth
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Am Coll Surg. 2003 Feb;196(2):222-5. doi: 10.1016/S1072-7515(02)01808-2.
Hereditary predisposition to colorectal cancer most often manifests itself as familial adenomatous polyposis from mutations of APC, or hereditary nonpolyposis colorectal cancer, resulting from mutations of MSH2, MLH1, MSH6, or other genes. Previously, we described a rare founder mutation MSH21906C > G in Ashkenazi Jews that was found in 8 of 1,345 individuals (0.6%) of Ashkenazi descent with colorectal cancer. This study seeks to characterize the proportion of individuals of Ashkenazi heritage with very early-onset colon cancer (diagnosed at age 40 or younger) that could be attributed to MSH21906C>G.
We analyzed the carrier frequency of MSH21906C>G in paraffin samples from 31 Jewish patients age 40 or less, diagnosed with colorectal cancer at Memorial Sloan-Kettering and lymphocyte-derived DNA from 10 patients. We did not select for family history. Genotyping for MSH21906C>G was performed by polymerase chain reaction and restriction enzyme digestion methods.
We detected the MSH2*1906G>C mutation in 3 of the 41 samples (7.14%) of patients who had colorectal cancer diagnosed at age 40 or younger. This incidence is significantly greater than the 8 in 1,345 (0.6%) we observed for cases of colorectal cancer in Ashkenazi Jews not selected for age (p = 0.004).
Although very rare in the population, MSH21906G>C is found at an increased frequency in young Jewish patients with colorectal cancer. These results suggest that testing for the MSH21906G>C mutation should be included in the evaluation of Ashkenazi Jewish individuals diagnosed with early-onset colon cancer.
结直肠癌的遗传易感性通常表现为因APC基因突变导致的家族性腺瘤性息肉病，或因MSH2、MLH1、MSH6或其他基因突变导致的遗传性非息肉病性结直肠癌。此前，我们在阿什肯纳兹犹太人中描述了一种罕见的奠基者突变MSH21906C>G，在1345名阿什肯纳兹血统的结直肠癌患者中有8人（0.6%）携带该突变。本研究旨在确定阿什肯纳兹血统中极早期结肠癌（40岁及以下确诊）患者中可归因于MSH21906C>G的比例。
我们分析了来自纪念斯隆凯特琳癌症中心的31名40岁及以下被诊断为结直肠癌的犹太患者石蜡样本以及10名患者淋巴细胞衍生DNA中MSH21906C>G的携带频率。我们未筛选家族史。通过聚合酶链反应和限制性内切酶消化方法对MSH21906C>G进行基因分型。
在41例40岁及以下被诊断为结直肠癌的患者样本中，我们检测到3例（7.14%）存在MSH2*1906G>C突变。这一发生率显著高于我们在未按年龄筛选的阿什肯纳兹犹太结直肠癌患者中观察到的1345例中有8例（0.6%）的发生率（p = 0.004）。
尽管在人群中非常罕见，但在年轻的犹太结直肠癌患者中，MSH21906G>C的发现频率有所增加。这些结果表明，在对被诊断为早发性结肠癌的阿什肯纳兹犹太个体进行评估时，应包括对MSH21906G>C突变的检测。
