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Support for pesticides playing a role in onset of multiple myeloma

Support for pesticides playing a role in onset of multiple myeloma. September 10, 2014 Ola Landgren, M.D., Ph.D. Chief, Myeloma Service Memorial Sloan-Kettering Cancer Center, New York www.MSKCC.org. What is multiple myeloma?. Multiple myeloma.

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Support for pesticides playing a role in onset of multiple myeloma

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  1. Support for pesticides playing a role in onset of multiple myeloma September 10, 2014 Ola Landgren, M.D., Ph.D. Chief, Myeloma Service Memorial Sloan-Kettering Cancer Center, New York www.MSKCC.org

  2. What is multiple myeloma?

  3. Multiple myeloma • Second most common blood cancer in the U.S.; over 83,000 affected in 2014 • Bone marrow cancer (plasma cells) • No established curative treatment; average survival 5-7 years

  4. Multiple myeloma: abnormal plasma cells in the bone marrow

  5. Multiple myeloma: lytic bone lesions Hillengass and Landgren. Leuk Lymphoma 2013

  6. Multiple myeloma: genetic heterogeneity within each patient Lohr et al. Cancer Cell 2014

  7. Multiple myeloma and its precursor “MGUS”

  8. “Monoclonal gammopathy of undetermined significance” (MGUS) Risk of developing multiple myeloma (0.5-1% per year) Cumulative risk (%) of myeloma Year of follow-up Kyle, Am J Med 1978; Turesson et al. Blood 2014

  9. Myeloma consistently preceded by precursor state “MGUS” >77,000 cancer free men and women; stored annual blood tests Multiple myeloma (n=71) Up to 10 years of follow-up Landgren et al. Blood 2009

  10. Risk factors for multiple myeloma; what are the causes?

  11. Risk factors for multiple myeloma; what are the causes? • Older age • Male gender • Family history of myeloma • African American descent • Obesity • Farming/pesticides

  12. Rusiecki et al, Env Health Perspect 2009

  13. Agricultural Health Study • Cancer incidence among pesticide applicators exposed to permethrin • Permethrin: synthetic pyrethroid insecticide widely used in agriculture and many U.S. homes and gardens • Prospective cohort 49,093 licensed pesticide applicators in Iowa and North Carolina • Self-administered questionnaires; average follow-up 9 years Rusiecki et al, Env Health Perspect 2009

  14. Agricultural Health Study: myeloma • No excess risk for non-Hodgkin lymphoma, leukemia, melanoma, cancers of the colon, rectum, lung, or prostate • 6-fold excess risk of multiple myeloma, compared with applicators reporting never used permethrin • Results based on 15 exposed cases • Findings similar across variety of alternative exposure metrics, exposure categories, and reference groups; warrants further evaluation Rusiecki et al, Env Health Perspect 2009

  15. Agricultural Health Study: MGUS Landgren et al, Blood 2009

  16. Agricultural Health Study: MGUS • 678 pesticide applicators (30-94 years) participated to assess risk of MGUS • Serum samples analyzed by electrophoresis; discrete or localized band subjected to immunofixation • Age-adjusted prevalence compared with MGUS prevalence in 9469 controls from Minnesota Landgren et al, Blood 2009

  17. Agricultural Health Study: MGUS • 38 had MGUS (prevalence 6.8%); age-adjusted prevalence 2-fold higher in pesticide applicators • Excess risk of MGUS associated with chlorinated insecticide dieldrin, the fumigant mixture carbon-tetrachloride/carbon disulfide, and the fungicide chlorothalonil • These findings support hypothesis that specific pesticides causatively linked to myelomagenesis Landgren et al, Blood 2009

  18. National Health and Nutritional Examination Survey (NHANES) Landgren et al, Leukemia 2014

  19. NHANES Study • Stored serum samples from 12,482 individuals >50 years (NHANES III and NHANES 1999–2004) • Serum samples analyzed by electrophoresis; discrete or localized band subjected to immunofixation • Define prevalence and risk factors of MGUS in large cohort representative of US population Landgren et al, Leukemia 2014

  20. NHANES Study • Prior study from Olmsted County, Minnesota, found 3.2% MGUS prevalence • NHANES overall MGUS prevalence was 2.4% (2.3% in whites) • Interestingly, MGUS prevalence was 3.1% in North/Midwest and 2.1% in South/West, respectively (P=0.052) Landgren et al, Leukemia 2014

  21. NHANES Study • According to SEER; death rates from multiple myeloma much higher in Minnesota than other regions of the country • The observed strong geographic disparity in prevalence of MGUS between the North/Midwest versus the South/West regions of U.S. has etiologic implications Landgren et al, Leukemia 2014

  22. Summary and conclusions

  23. Summary and conclusions • Studies show pesticide exposure associated with MGUS and multiple myeloma • Geographic disparity of MGUS/multiple myeloma: high prevalence in North/Midwest • Ongoing studies to confirm findings and better understand underlying mechanisms

  24. Selected ongoing studies (collaborators) • Agricultural Health Study: part II (NCI) • Agent Orange exposed veterans (CDC/VA) • World Trade Center rescue workers (FDNY/Albert Einstein College of Medicine)

  25. Thank you for your attention! Ola Landgren, M.D, Ph.D. Chief, Myeloma Service Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY 10065, USA Email: landgrec@mskcc.org Phone: 212-639-5126

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