1. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Identifying Lung Cancer Risks

2. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Lung Cancer Lung cancer is the leading cause of death among cancer victims in the United States. –It claims more lives than colon, prostate, and breast cancer combined. –Smoking is the most significant factor for lung cancer. But, only 10% of ever smokers have lung cancers.

3. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Observed and projected lung cancer death rates, United States, 1930–2003 The observed death rates are based on data published by the National Center for Health Statistics, Centers for Disease Control. The dotted lines represent straight line projections of the observed slope from 1950–1975 in men and from 1975–1990 in women. (http://tobaccocontrol.bmj.com)

4. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 National Expenditures for Medical Treatment for the Most Common Cancers Based on Cancer Prevalence in 1998 and Cancer-Specific Costs for 1997-1999, projected to 2004 using the medical care component of the Consumer Price Index. (http://progressreport.cancer.gov)

5. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Survival Rate is Low for Lung Cancer Type5-Year survival for all stages Early Detection Late Detection Lung14.9%48.7%21% Breast86.6%97.0%23.2% Prostate97.5%100%34.0% Colon62.3%90.1%9.2%

6. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Lung Cancer Two interesting questions: 1.Are the remaining 90% of ever smokers genetically protected from cancer diseases? 2.Are there factors other than smoking attributed to lung cancers? 3.How does second-hand smoking contribute to cancer? Case control studies –Cases are group of lung cancer patients –Controls are group of normal people

7. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Never Smokers Identify causal factors for lung cancer other than smoking –Environmental factors –Genetic factors: metabolic pathway genes –Interaction between environmental factors and the metabolic pathway genes Subjects under investigation –Never smokers Smoking is a dominating factor, may confound genetic factors and environmental agents

8. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Interactions of Genes to Lung Cancer Histological Information SNP Microarray Lung Tissue Genetic Information Blood Sample

9. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Microarray Technology: Genes Attributed to Cancer

10. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Microarray Experiment To understand the roles certain genes play in the progression of cancer, cancer tissue is taken and used in microarray experiment.

11. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Microarray Experiment “Normal” and tumor cells are grown in two separate populations. CDNA from the two populations are dyed with green/red fluorescence. Two populations are incubated with the chip. After scanning the chip, the color represents the ratio of two populations.

12. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Gene Expression There are over 10,000 different probes used. Each dot represents the location of a gene probe.

13. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Co-regulated Genes Intensities of genes change together if they are regulated by the same biological functions.

14. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 GEO Databases GEO Databases http://www.ncbi.nlm.nih.gov/geo/

15. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Single Nucleotide Polymorphisms: Genomic Variations in Disease

16. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Single Nucleotide Polymorphisms SNPs are single bases at a particular locus where individual people have differences in their sequences. –SNPs are another form of genomic variation in population

17. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Population Based Each ethnic group has its own collection of SNPs. Human SNPs classified by major or minor alleles. –major alleles are common for all human –minor alleles are useful within an ethnic group You should know the average frequency of alleles of the population you are studying!!

18. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 HapMap Project The international HapMap consortium has identified >1 million SNPsHapMap –Samples from four populations –1 SNP every 2 kb of genomic sequence

19. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Use SNPs as Markers SNPs are reliable markers –Most genes contain at least one SNP –Combinations of alleles are associated with particular disease. Study of evolution –Understand how a subpopulation adapted to the environment by comparing the differences in their SNPs DNA fingerprinting for criminal or parental verification. Genotype-specific medication

20. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Example 2: Demographic Distributions Comparison between case and control –Case: a patient who has been diagnosed with lung cancer –Control: person without any cancer

21. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 Example 2: Genomic Variations Now, we feel comfortable comparing two populations Human inherits a pair of chromosomes, so the variations are paired as GSTP1 II

22. ©Edited by Mingrui Zhang, CS Department, Winona State University, 2008 SNPs Databases http://www.ncbi.nlm.nih.gov/SNP/ Oops! Reprocess mine?