Genetic Factors

1
Genetic Factors

• Genes and environmental factors impact cancer
  incidence
• Environment greater impact
• www.cancer-genetics.org

2
Inherited Cancers

• Parent to child transmission
• Genes inherited in dominant fashion (Mendelian
  genetics)
• Inherited gene almost always leads to cancer
• Characteristics
• Occurs early in life
• Lead to multiple tumors

3
Genetic vrs. Sporadic Incidence

• Many genetic factors but most sporadic (random)
• Colon cancer
• 2 rare genes which both contribute about 1
• Over 95 colon cancers represent non-inherited,
  sporadic disease

4
Genetic Predisposition

• Transmitted in recessive form (Mendelian
  genetics)
• Requires two copies of the gene to generate
  disease, one from each parent
• Not specific towards any cancer type
• Affect stability of cellular genetic material
• Inhibit function of the immune system

5
Familial Susceptibility

• Type of cancer
• Minor overall incidence
• Important for individual families
• No clear explanation (hypothesis- enzymes which
  break down smoke toxins inhibited)

6
Xeroderma Pigmentosum (XP)

• Inherited DNA repair deficiency (recessive)
• Patients suffer xtreme skin sensitivity to
  ultraviolet (UV) light, abnormal skin
  pigmentation, and high frequency of skin cancers,
  especially on sun-exposed skin.
• Neurologic involvement is often part of a
  phenotypic spectrum
• The worldwide frequency of XP is estimated at 1
  in 250,000.

7
XP cases

• Sunlight-induced dermatologic abnormalities in a
  patient with xeroderma pigmentosum.
• Typical skin manifestation of xeroderma
  pigmentosum with numerous areas of
  hypopigmentation and freckles (ie, solar
  lentigines) with different intensities of
  pigmentation.

8
Retinoblastoma (RB)

• Inherited disorder (dominant), accounts for 10
  of all retinoblastomas
• Affects both eyes
• Associated with a long-term predisposition to
  other types of cancer
• 90 of all retinoblastoma cases are diagnosed
  within the first 3 years of the child's life

9
RB symptoms

• 1st leukocoria, whitening of the pupil that
  looks like a "cat's eye
• Most common sign of RB- present in 60 patients

10
Li-Fraumeni Syndrome (LFS)

• 2-4 cases/100,000 (low) 400 families worldwide
• But, probability of tumors occurring by AGE 30 is
  50 compared to normal population 1
• Greatly increases risk of developing several
  uncommon types of cancer osteosarcoma, soft
  tissue sarcoma, breast cancer, brain tumors,
  adrenocortical carcinoma, and leukemia.