0f2d9b8c-69e1-4d80-949a-73b137424464.json

{
 "id": "0f2d9b8c-69e1-4d80-949a-73b137424464",
 "disease": {
  "id": "H00020",
  "names": [
   "Colorectal cancer"
  ],
  "dbLinks": {
   "icd10": [
    "C18",
    "C19",
    "C20"
   ],
   "mesh": [
    "D015179"
   ]
  },
  "category": "Cancer",
  "description": "Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes (TSG). Two major mechanisms of genomic instability have been identified in sporadic CRC progression. The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. The second, known as microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes have germline mutations in specific genes (mutation in the tumour suppressor gene APC on chromosome 5q in FAP, mutated DNA mismatch repair genes in HNPCC)."
 },
 "article": {
  "id": "23896379",
  "text": "BACKGROUND:\nThe p.I1307K adenomatous polyposis coli (APC) gene variant, prevalent among Ashkenazi Jews, may increase the risk for colorectal neoplasia. We studied the clinical importance of screening for this polymorphism in 3305 Israelis undergoing colonoscopy.\n\nPATIENTS AND METHODS:\nClinical data regarding potential risk factors for colorectal cancer (CRC) were collected from individuals undergoing colonoscopic examination at the Tel-Aviv medical center. The APC p.I1307K was detected using real-time PCR (polymerase chain reaction) from DNA extracted from peripheral mononuclear cells.\n\nRESULTS:\nThe overall prevalence of the p.I1307K polymorphism was 8.0% (10.1% among Ashkenazi and 2.7% among Sephardic Jews, p\u003c0.001). The overall adjusted odds ratio (OR) for colorectal neoplasia among carriers was 1.51 (95% confidence intervals (CI), 1.16-1.98). Among average risk Ashkenazi Jews, the adjusted OR was 1.75 (95% CI 1.26-2.45). A multiplicative interaction was identified between Ashkenazi ethnicity and APC p.I1307K carrier status (P(INTERACTION) = 0.055). The histopathological features of adenomas and carcinomas did not differ between carriers and non-carriers.\n\nCONCLUSIONS:\nThe APC p.I1307K gene variant is an important risk factor for colorectal neoplasia in average risk Ashkenazi Jews. Carriers in this group should be considered for screening colonoscopy at the age of 40, to be repeated every 5 years, similar to recommendations in individuals with family history of colorectal cancer."
 },
 "questions": [
  {
   "id": "37fdb837-2683-431f-a3b1-6a37323088f8",
   "text": "What are the risk factors of Colorectal Cancer?",
   "answers": [
    {
     "answer_start": 1194,
     "text": "APC p.I1307K gene variant"
    },
    {
     "answer_start": 633,
     "text": "p.I1307K polymorphism"
    }
   ]
  }
 ]
}