see also:

• neoplasia / cancer / tumours

• carcinogenesis

• 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
  • cancer-associated infections, including human papilloma virus (HPV), hepatitis B virus, hepatitis C virus
    • HPV vaccination has markedly reduced the incidence of some cancers
  • ultraviolet radiation skin cancer risk
  • 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
  • regular consumption of hot beverages / meals
  • physical inactivity
• 5% of cancers are now thought to be due to CT scans
  • a US 2025 study suggest that CT scans (esp. CTAP and CT chest) now may account for 5% of all cancers in the US, particularly, lung, breast, colon, leukaemia, bladder cancers based upon risk models from the National Academy of Sciences’ Biologic Effects of Ionizing Radiation (BEIR) VII report on the various cancer risks for each organ²⁾

• hereditary cancers are a minority, and many of these genes are linked to increased risk rather than certainty
• “cancer families”
  • eg Lynch Syndrome (aka hereditary non-polyposis colorectal cancer (HNPCC))
    • autosomal dominant
    • increased risk of cancers:³⁾
      • 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
  • eg. BRCA1 and BRCA2 mutations
    • autosomal dominant, occur in 1 in 500 women and are present in 5-10% of patients with breast cancers (half of genetic cases)
    • BRCA1: breast, ovarian, bowel and prostate cancers and tends to cause triple negative breast cancer
    • BRCA2: breast, ovarian, pancreatic and prostate cancers but also mild increase in melanoma risk
  • eg. POT1 Tumor Predisposition Syndrome (POT1-TPD)
    • autosomal dominant; 1 in 3000 people and 0.12% of those with cancers;
    • mainly haematopoietic such as lymphoma (8x risk), leukaemia (16x risk CLL), JAK2 somatic mutation risk but also melanoma (7x risk), glioma and others
  • others by risk of type of tumour and known gene mutations:
    • breast/ovarian/pancreatic/prostate: BRCA1, BRCA2, PALB2, ATM, CHEK2
    • colorectal/endometrial: MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MUTYH, SMAD4, BMPR1A, POLE, POLD1
    • diffuse gastric and lobular breast cancer: CDH1
    • MEN2 / thyroid: RET
    • pheochromocytoma/paraganglioma: VHL, SDHB, SDHD, SDHC, SDHA
    • Cowden syndrome: PTEN
    • Li Fraumeni syndrome (LFS): TP53
      • individuals with LFS have a highly elevated risk of developing cancer, sometimes exceeding 90% for women and 70 for men, often occurring before the age of 40
      • an annual whole-body screening MRI may be recommended
• polyposis coli (AD)
• melanoma risk
  • 8% have a first degree family member with melanoma
  • fair skin with tendency to freckling, blonde or red hair, blue eyes phenotype
  • rare disorders that have increased risk of melanoma:
    • POT1_mutations
    • xeroderma pigmentosum (XP)
    • retinoblastoma
    • Li-Fraumeni syndrome
    • Werner syndrome
    • BRCA2 breast cancer gene increases risk mildly
• multiple endocrine neoplasia
• Down's syndrome → leukaemia
• twin with Hodgkin's lymphoma ⇒ 99x risk Hodgkin's lymphoma
• parent or sibling with Hodgkin's ⇒ 7x risk Hodgkin's lymphoma
• rare familial disorders such as Li Fraumeni synd (TP53 gene mutation), Cowden's synd (PTEN mutation), Peutz-Jegher's synd., ataxia telangiectasia increase risk of breast cancer
• 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 smokers⁴⁾

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

• 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;
• hepatitis B virus, hepatitis C virus → hepatocellular Ca
• HIV + CMV → Kaposi's (but via impaired immune system?)
• HTLV-1 → T cell lymphoma?

• 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 → Barrett's oseophagitis → oesophageal Ca
• drinking hot beverages → SCC oesophageal Ca
• malaria + EBV / glandular fever / infectious mononucleosis ⇒ endemic Burkitt's lymphoma