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

2. What is multiple myeloma?

3. Bone marrow cancer (plasma cells)
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. Landgren et al, Leukemia 2014
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. Landgren et al, Leukemia 2014
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. Landgren et al, Leukemia 2014
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
Phone: