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Marin Biospecimen Studies Revisiting the Past to Move into the Future

Marin Biospecimen Studies Revisiting the Past to Move into the Future. Christopher C. Benz, MD Director, Cancer and Developmental Therapeutics Program Buck Institute for Age Research Adjunct Professor, University of California, San Francisco. Marin Community Forum October 15, 2009.

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Marin Biospecimen Studies Revisiting the Past to Move into the Future

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  1. Marin Biospecimen Studies Revisiting the Past to Move into the Future Christopher C. Benz, MD Director, Cancer and Developmental Therapeutics Program Buck Institute for Age Research Adjunct Professor, University of California, San Francisco Marin Community Forum October 15, 2009

  2. Marin Women’s Study Biospecimens, Avon, & the Buck Institute

  3. Community-based Marin Women’s Study (MWS) October 23, 2002 BUCK SYMPOSIUM

  4. Community-based Marin Women’s Study (MWS) October 23, 2002 BUCK SYMPOSIUM Community Partnership MCDHHS (Epidemiology) BUCK Institute Sutter Health-MGH Kaiser-Marin Advocates MWS Steering Committee (2005-present)

  5. Community-based Marin Women’s Study (MWS) Launched October 23, 2006… October 23, 2002 BUCK SYMPOSIUM Community Partnership MCDHHS (Epidemiology) BUCK Institute Sutter Health-MGH Kaiser-Marin Advocates (www.mwstudy.org) MWS Steering Committee (2005-present)

  6. July 2007: AVON Foundation Funds MWS Biospecimen Study Lee Ann Prebil, MPH, PhD Principal Investigator, AVON Foundation Study Community Epidemiology Program, MCDHSS • Consent to give saliva sample with enrollment into MWS. • Questionnaire data on individual breast cancer risk factors to be correlated with Mammographic Density and saliva steroid levels on 2,000 MWS study enrollees. • Buck Institute provides biorepository space and services (C. Benz, study collaborator) Mark Powell, MD Biorepository Director, MWS Community Epidemiology Program, MCDHSS News- Friday, August 17, 2007 By Ronnie Cohen “A mouth-watering cancer study” County officials believe saliva research more than just spittin’ into the wind…

  7. AVON FOUNDATION GRANT:“The link between first pregnancy, breast density, & novel measures of endogenous hormone levels.” Questionnaire-in-dept MWS information about reproductive history (parity, age at each birth, pregnancy events, birth weights, breast feeding) exogenous hormone use, alcohol consumption, diet, SES, etc. Breast density-using digitized screening mammograms, volumetric compositional breast density will be determined by collaborating SFMR.

  8. Mammographic Density: a key breast cancer risk factor and MWS parameter % Mammographic Density Collagen-rich dense breast tissue 4-6 fold higher breast cancer risk 0% 1-10% 10-25% 25-50% 50-75% 75-100% Couzin, Science 309, 2005 Boyd et al., NEJM 347, 2002

  9. AVON FOUNDATION GRANT:“The link between first pregnancy, breast density, & novel measures of endogenous hormone levels.” Questionnaire-in-dept MWS information about reproductive history (parity, age at each birth, pregnancy events, birth weights, breast feeding) exogenous hormone use, alcohol consumption, diet, SES, etc. Breast density-using digitized screening mammograms, volumetric compositional breast density will be determined by collaborating SFMR. Biospecimens-using saliva samples to help understand why breast cancer risk factors (questionnaire & breast density data) do not apply to all women in the same way.

  10. AVON FOUNDATION GRANT:“The link between first pregnancy, breast density, & novel measures of endogenous hormone levels.” Questionnaire-in-dept MWS information about reproductive history (parity, age at each birth, pregnancy events, birth weights, breast feeding) exogenous hormone use, alcohol consumption, diet, SES, etc. Breast density-using digitized screening mammograms, volumetric compositional breast density will be determined by collaborating SFMR. Biospecimens-using saliva samples to help understand why breast cancer risk factors (questionnaire & breast density data) do not apply to all women in the same way. SPITTING… for competition, tasting, fun &… SCIENCE!

  11. MWS/AVON STUDY BIOSPECIMENS early morning saliva samples As a biologic fluid, saliva offers advantages over biopsy and blood samples… -- collected non-invasively (at home). -- cost-effective means of screening large populations. -- proven bioassay applications: from cell-free component, sex steroid levels reflect blood levels. from cells, DNA detection of individual gene variations (SNPs). Buck Institute:Bank and process all incoming saliva samples (~60/week) for measurement of steroid levels and future DNA studies.

  12. Marin high school volunteers assemble saliva kits 20K saliva kits for assembly & MWS distribution MWS participants mail saliva samples to Buck

  13. Marin high school volunteers assemble saliva kits 20K saliva kits for assembly & MWS distribution MWS participants mail saliva samples to Buck Mark Powell (MCDHHS) and Rachel Puckett (Buck Institute) log the bar-coded samples (~20/day) into computer database and store in -80C freezers in secured Buck biorepository

  14. SALIVA SAMPLE PROCESSING: Rachel withdraws frozen saliva samples and spins tubes to separate cell-free fluid (for steroid levels) from cell pellets (for DNA analysis)

  15. SALIVA SAMPLE PROCESSING: Rachel withdraws frozen saliva samples and spins tubes to separate cell-free fluid (for steroid levels) from cell pellets (for DNA analysis) Cell-free fluid is measured and re-frozen in smaller vials; DNA is then extracted from cell pellets and analyzed for purity and integrity

  16. MWS/AVON STUDY BIOSPECIMENS early morning saliva sample?

  17. MWS/AVON STUDY BIOSPECIMENS early morning saliva sample? Good volume, wrong biospecimen!

  18. MWS/AVON: Salivary Hormone Levels (n327) Completed analysis of all 2,000 samples pending…

  19. MWS Biospecimens What’s next?

  20. Marin Breast Cancer Risk Factors Include: • Average >2 alcoholic drinks/day • Excess risk only for ER+ breast cancer • HRT use and ER+ breast cancer October 23, 2002 BUCK SYMPOSIUM Wrensch et al., Breast Cancer Res. 5: R88-102, 2003. Benz et al., Cancer Epi. Bio. Prev. 12: 1523-1527, 2003. Hwang et al., Arch. Surg. 140: 58-62, 2005.

  21. Marin Breast Cancer Risk Factors Include: • Average >2 alcoholic drinks/day • Excess risk only for ER+ breast cancer • HRT use and ER+ breast cancer • Role of individual gene variations? October 23, 2002 BUCK SYMPOSIUM Community-based Marin Risk Factor Study cases (n=336) vs. matched controls (n=321), 1997-1999

  22. Chromosomes & Genes 23 Human chromosome pairs Chromosome pair • Human DNA is 99.9% identical; 0.1% encodes our different geneologies & health risks. • Normal gene variations can be identified as Single Nucleotide Polymorphisms (SNPs).

  23. October 23, 2002 BUCK SYMPOSIUM Community-based Marin Risk Factor Study cases (n=336) vs. matched controls (n=321), 1997-1999 Marin Breast Cancer Risk Factors Include: • Average >2 alcoholic drinks/day • Excess risk only for ER+ breast cancer • HRT use and ER+ breast cancer • Role of individual gene variations? Buccal cells collected for DNA analysis • K. Dalessandri et al. & InterGenetics Inc. • 429 cases & controls: 22 SNP genotypes studied • Do Individual gene variations (SNPs) predict risk?

  24. 1997-1999 Marin Adolescent Risk Factor Study:YES, individual gene variations (SNPs) predict breast cancer risk! Presented at 2008 San Antonio Breast Cancer Symposium: “Validation of OncoVue, a new individualized breast cancer risk estimator in the Marin County, California adolescent risk study.” To be presented at 2009 San Antonio Breast Cancer Symposium: “Breast cancer risk assessment in the high risk Marin County population using OncoVue compared to SNPs from genome wide association studies.”

  25. MWS Biospecimens Do individual gene variations (SNPs) predict risk independent of mammographic density?

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