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1. Introduction
2. Background
3. Estimates of American Cancer Society for 2005
4. Gene/environment interactions
5. Goals of this presentation
6. Biomarkers- from exposure to disease
7. Parts of presentation
8. Part I: genetic susceptibility of lung cancer risk
9. The paradigm
10. Polymorphic metabolizing genes in lung cancer
11. Methods - case-control study
12. Methods - information and analyses
13. SNP and lung cancer - MnSOD
14. Pyrosequencing for MnSOD polymorphism
15. Ala9Val MnSOD polymorphism results
16. GSTP1 and early lung carcinoma in women
17. Multivariate analysis for GSTP1 polymorphism
18. mEH polymorphism and cigarette smoking
19. Results of the study
20. Lung cancer risk of low mEH and other genotypes
21. Putative mechanism
22. DNA repair and cancer risk
23. Mammalian DNA repair systems
24. Genes in DNA repair pathways
25. Role of ERCC2 polymorphism
26. Model evaluating ERCC2 and smoking
27. Role of XRCC1 polymorphism
28. Model evaluating XRCC1 and smoking
29. Role of ERCC1 polymorphism
30. Model evaluating ERCC1 and smoking
31. Summary: part I
32. Part II: DNA repair and treatment response
33. DNA repair polymorphisms and treatment response
34. DNA repair polymorphisms and overall survival
35. Adjusted hazard ratios
36. Kaplan-Meier curves of the ERCC2 polymorphism
37. Kaplan-Meier curves of the XRCC1 polymorphism
38. Kaplan-Meier curves of the ERCC1 polymorphism
39. DNA repair polymorphism and GI toxicity
40. ERCC1 polymorphism and GI toxicity
41. Vitamin D and survival in early stage NSCLC
42. Proposed mechanism for vitamin D and cancer
43. Vitamin D is important at treatment initiation
44. Patient and tumor characteristics
45. Treatment and follow-up characteristics
46. Recurrence time
47. Overall survival
48. Summary: part II
49. Where do we go from here?
50. Possible future applications
51. LCS research team (1)
52. LCS research team (2)
53. Grant support

Topics Covered

• The influence of host factors on individual susceptibility to tobacco smoke
• The pleiotropic genes that control activation (Phase I) and detoxification (Phase II) of potential carcinogens
• Effects of the metabolism of environmental compounds on the lipophilic properties of a molecule and the introduction of electronegative moieties within the molecule on carcinogenic potential
• Other susceptibility factors related to defects in DNA repair, alterations in tumor suppressor genes and alterations in tumor invasiveness factors
• Polymorphisms in genes and the association of this with lung cancer development
• The role of inherited polymorphisms of genes involved in xenobiotic metabolism, DNA repair and tumor suppression/invasion (alone and in combination) in lung cancer risk, and modification of this risk by environmental factors such as smoking and diet

Links

Series:

• Gene-Environment Interactions

Categories:

• Cancer
• Genetics & Epigenetics

Therapeutic Areas:

• Oncology

Talk Citation

Publication History

• Published on October 1, 2007
• Archived on February 25, 2021

Financial Disclosures

• Dr. Christiani has served as a paid expert on behalf of victims (plaintiff) cases against tobacco companies.