Lee Jasmine, Xiao Yin-Yi, Sun Yan Yu, Balderacchi Jasminka, Clark Bradley, Desani Jatin, Kumar Vivek, Saverimuthu Angela, Win Khin Than, Huang Yiwu, Xu Yiqing
Division of Hematology and Oncology, Department of Internal Medicine, Maimonides Medical Center, 6300 8th Avenue, Brooklyn, NY, 11220, USA.
Department of Health Policy and Management, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
BMC Cancer. 2017 Dec 13;17(1):843. doi: 10.1186/s12885-017-3799-y.
The prevalence of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is 2 to 5% in the Caucasian population. HNPCC is caused by genomic mutations in DNA mismatch repair genes (MMR), namely MLH1, MSH2, MSH6, PMS2, and EPCAM. A non-hereditary, acquired process of hypermethylation of the MLH1 promoter can also lead to silencing of MLH1 protein expression. Diagnosis of HNPCC in patients with colorectal and other related cancers is important in the clinical treatment and surveillance of related cancers. The prevalence and clinical characteristics of HNPCC in Asian colorectal cancer patients has been reported in small studies and unique features have been suggested.
We retrospectively reviewed the clinical characteristics of Asian patients who were diagnosed of colon cancer between 1/2002 and 6/2015, and performed IHC for four MMR protein expressions on tumor specimens as a screening test for HNPCC, followed by confirmatory tests of genomic sequencing and hypermethylation analysis.
One hundred forty-three patients were identified. Thirty-one patients were diagnosed younger than 50 years old, while 112 patients were diagnosed older than 50 years old. Six cases of HNPCC were found with a prevalence of 4.19%. The prevalence in the group of patients diagnosed younger than 50 years old is 16.1%, and that in patients diagnosed older than 50 years old is 0.89%. All patients with HNPCC had family histories of colon or gastric cancer. Tumor locations in the HNPCC patients were predominantly in the descending or sigmoid colon (67%). Half of the HNPCC patients had MSH6 mutations. Hypermethylation of the MLH1 gene was only present in 2.80% of the patients.
The prevalence of HNPCC is high in patients younger than 50 years old and extremely low in those older than 50 years old. These results may be useful in the future development of guidelines for HNPCC laboratory screening among Asian patients. The pathological and clinical features of HNPCC in this group of Asian immigrant patients are more similar to those reported on Asian patients in their home countries than to Caucasian patients in Western countries, and will warrant further large-scale evaluation.
遗传性非息肉病性结直肠癌（HNPCC）在白种人群中的患病率为2%至5%。HNPCC由DNA错配修复基因（MMR）即MLH1、MSH2、MSH6、PMS2和EPCAM的基因突变引起。MLH1启动子的非遗传性、后天性高甲基化过程也可导致MLH1蛋白表达沉默。对结直肠癌及其他相关癌症患者进行HNPCC诊断，对相关癌症的临床治疗和监测具有重要意义。小规模研究报道了亚洲结直肠癌患者中HNPCC的患病率及临床特征，并提出了一些独特之处。
我们回顾性分析了2002年1月至2015年6月期间被诊断为结肠癌的亚洲患者的临床特征，并对肿瘤标本进行了4种MMR蛋白表达的免疫组化检测，作为HNPCC的筛查试验，随后进行基因组测序和高甲基化分析的确诊试验。
共确定了143例患者。31例患者诊断时年龄小于50岁，112例患者诊断时年龄大于50岁。发现6例HNPCC患者，患病率为4.19%。诊断时年龄小于50岁的患者组患病率为16.1%，诊断时年龄大于50岁的患者组患病率为0.89%。所有HNPCC患者均有结肠癌或胃癌家族史。HNPCC患者的肿瘤部位主要在降结肠或乙状结肠（67%）。一半的HNPCC患者有MSH6突变。MLH1基因的高甲基化仅在2.80%的患者中出现。
HNPCC在年龄小于50岁的患者中患病率较高，在年龄大于50岁的患者中患病率极低。这些结果可能有助于未来制定亚洲患者HNPCC实验室筛查指南。这组亚洲移民患者中HNPCC的病理和临床特征与其本国亚洲患者的报道更相似，而与西方国家的白种患者不同，值得进一步大规模评估。
