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neoplasia_aetiology

neoplasia / cancer aetiologic factors

introduction

  • carcinogenesis

modifiable causes

  • 40% of cancers in adults are thought to be attributable to potentially modifiable lifestyle factors:
    • Cigarette smoking (19% of cases and 29% of cancer deaths)
    • Excess body weight (8% of cases and 7% of cancer deaths)
    • Alcohol consumption (6% of cases and 4% of cancer deaths)
      • risk is mainly breast and colorectal cancers, followed by cancers of the rectum, mouth and throat, liver, oesophagus and larynx
      • risk becomes significant when intake is in excess of 3-6 drinks per week
    • Secondhand cigarette smoke
    • Other smoke including exposure to bushfire and other fire smoke with fire fighters particularly at risk
    • Six cancer-associated infections, including HPV
    • Ultraviolet radiation
    • Consumption of red and processed meat
      • it is possible that the red meat and caviar from certain animals which produce the Neu5Gc sugar via the CMAH gene creates an inflammatory immune response in humans (humans do not produce this sugar and thus it may be regarded as a foreign immune substance) - but not all red meat contains this sugar 1)
    • Low consumption of fruits, vegetables, dietary fibre, and calcium
    • Physical inactivity

genetic predisposition

  • “cancer families” - breast - colon - ovarian;
    • eg Lynch Syndrome (aka hereditary non-polyposis colorectal cancer (HNPCC))
      • autosomal dominant
      • increased risk of cancers:2)
        • colon and rectum (80% risk) - accounts for 3-5% of colorectal cancer (bowel cancer)
        • uterus (20-60% risk)
        • stomach (11-19% risk)
        • ovaries (9-12% risk)
        • liver, gallbladder ducts (2-7% risk)
        • upper urinary tract (4-5% risk)
        • small intestine (1-4% risk)
        • brain (1-3% risk)
        • skin, pancreas, breast, prostate, kidney
      • caused by variations in the MLH1, MSH2, MSH6, PMS2, or EPCAM genes
  • polyposis coli (AD)
  • xeroderma pigmentosum
  • retinoblastoma
  • melanoma
  • multiple endocrine neoplasia
  • Down's → leukaemia
  • twin with Hodgkin's ⇒ 99x risk HL
  • parent or sibling with Hodgkin's ⇒ 7x risk HL
  • tall women appear to have 16% increase in cancer risk for every 10cm height
    • taller women were at increased risk of cancers of the rectum, breast, endometrium, ovary, kidney and of malignant melanoma, non-Hodgkin lymphoma and leukaemia.
    • perhaps related to a common mechanism in early life, or more cells available to mutate, or perhaps due to higher socio-economic differences (drink more alcohol, later age at menarche, fewer children and later age at 1st child) although taller women were less obese and less likely to be current smokers3)

carcinogenic agents or carcinogens

  • direct acting chemicals: cytotoxics;
  • immunosuppressants
  • procarcinogen chemicals: aromatic HC; aflatoxin; nitrosamines; cigarette smoke; chimney soot (scrotal cancer in chimney sweeps);
  • physical: ionising rad.; UV; asbestos;

human oncogenic viruses

  • EBV / glandular fever / infectious mononucleosis → Burkitt's lymphoma, post-transplant lymphoma, Hodgkin's lymphoma, NHL, nasopharyngeal Ca
  • HSV type 2 → Cx Ca?
  • papovaviruses (genital wart viruses esp. types 16/18) → papilloma (skin, larynx), cervical Ca, breast, colorectal, pharyngeal, penile, etc;
  • hep B → hepatocell. Ca
  • HIV + CMV → Kaposi's (but via impaired immune system?)
  • HTLV-1 → T cell lymphoma?

chronic illness, inflammation or repetitive tissue injury

  • Marjolin's ulcer (SCC) in ch. varicose ulcers, sinuses of ch. osteomyelitis & old burn scars;
  • Ca tongue due to tertiary syphilitic glossitis;
  • < 4% gastric ulcers → malignant - ?? causal;
  • 4% ulcerative colitis → colon Ca; Crohn's occas → small bowel Ca;
  • cholelithiasis rarely → GB Ca but present in 75%! 1% Paget's bone → osteosarcoma;
  • schistosomiasis → bladder Ca; cirrhosis → liver Ca; I def. goitre → thyroid Ca?;
  • Plummer-Vinson synd. (Fe-def. anaemia, glossitis) → post-cricoid Ca;
  • GOR or drinking hot tea → oesophageal Ca
  • malaria + EBV ⇒ endemic Burkitt's lymphoma
neoplasia_aetiology.txt · Last modified: 2023/01/18 22:15 by gary1

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