16. Interaction of environmental and genetical factors in disease development

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  • Most diseases are due to a combination of genetic and environmental factors
  • We cannot change the genetic factors but we can change environmental factors
  • Certain genes can increase the risk of disease after exposure to certain environmental factors
    • Exposure + susceptible genotype -> high risk
    • Exposure + not susceptible genotype -> moderate risk
    • No exposure + susceptible genotype -> low risk
    • No exposure + not susceptible genotype -> low risk
  • Gene-environment interaction studies
    • Describe how genetic and environmental factors influence the risk of developing disease
    • The exposome = all the environmental exposures of a person
    • The phenome
      • = the phenotype of all cells in a person
      • = the sum of the exposome and the genome
  • Concept is demonstrated by an epidemiological study of oven workers
    • Oven workers at a steel company are exposed to PAH emissions from the ovens. The amount of exposure depends on where they work
    • Result of study: workers who smoked on their free time had more chromosomal damage as a result of oven emission exposure
    • Conclusion: Smoking reduced DNA repair capacity, increasing the susceptibility to PAH
  • Single nucleotide polymorphisms (SNPs)
    • = point mutations in a single nucleotide
    • Basically means small variations in genes between individuals
    • Certain SNPs are associated with increased risk of diseases
      • SNPs of GSTM1 – increased risk for colorectal cancer
      • SNPs of XRCC1 – increased risk for colorectal cancer
      • SNPs of NAT2 – increased risk for colorectal cancer
      • SNPs of p53 – increased risk for colorectal cancer
      • A1 variant of DRD2 – increased risk for cervical cancer and head and neck cancer
  • See also topic 28 (molecular epidemiology) in public health 1 + 2