{'fraction_non_alphanumeric': 0.032474804031354984, 'fraction_numerical': 0.012318029115341545, 'mean_word_length': 5.3144876325088335, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Germline mutation analysis of the transforming growth factor β receptor type II (TGFBR2) and E-cadherin (CDH1) genes in early onset and familial colorectal cancer

Editor—Genetic factors are clearly implicated in colorectal cancer (CRC) susceptibility, with 10% of all cases having an affected first degree relative and suggestions that up to 20% of all colorectal cancers occur in susceptible people. Identification of the molecular basis for familial adenomatous polyposis (FAP) and hereditary non-polyposis colon cancer syndrome (HNPCC) has provided insights into the mechanisms of colorectal cancer susceptibility and illustrated how somatic mutations in familial cancer genes are frequently implicated in sporadic cancers. FAP has a characteristic phenotype with profuse colorectal polyposis, and although variant attenuated forms of FAP are described, germline APC gene mutations are a rare cause of colorectal cancer. HNPCC is characterised by early onset CRC and, in some kindreds, endometrial, gastric, ovarian, pancreatic, and urinary tract cancers.1 Germline mutations in mismatch repair genes (MMR) such as MSH2 , MLH1 , PMS1 , PMS2 , and MSH6 account for many, but not all, HNPCC kindreds. Most (>90%) HNPCC kindreds with germline MMR mutations have a MSH2 or MLH1 mutation. Germline MMR gene mutations have also been described in isolated early onset colorectal cancer (EOCRC) or familial non-HNPCC CRC.2-4 However, it is estimated that FAP and HNPCC only account for ∼3% of CRC cases and studies of early onset and non-HNPCC familial cases have indicated that most such cases do not have germline MMR gene mutations or evidence of tumour microsatellite instability (MSI) (the hallmark of tumour MMR gene inactivation).2 4-6 Candidate gene approaches to identify further …