16. Interaction of environmental and genetical factors in disease development

• 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