Support for pesticides playing a role in onset of multiple myeloma September 10, 2014 Ola Landgren,...
Transcript of Support for pesticides playing a role in onset of multiple myeloma September 10, 2014 Ola Landgren,...
Support for pesticides playing a role in onset of multiple myeloma
September 10, 2014Ola Landgren, M.D., Ph.D.Chief, Myeloma ServiceMemorial Sloan-Kettering Cancer Center, New Yorkwww.MSKCC.org
• 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
Multiple myeloma
Multiple myeloma: abnormal plasma cells in the bone marrow
“Monoclonal gammopathy of undetermined significance” (MGUS)
Kyle, Am J Med 1978; Turesson et al. Blood 2014
Risk of developing multiple myeloma (0.5-1% per year)
Cum
ulati
ve ri
sk (%
) of m
yelo
ma
Year of follow-up
Myeloma consistently preceded by precursor state “MGUS”
Landgren et al. Blood 2009
Multiple myeloma
(n=71)>77,000 cancer free men
and women; stored annual blood tests
Up to 10 years of follow-up
•Older age•Male gender• Family history of myeloma•African American descent•Obesity• Farming/pesticides
Risk factors for multiple myeloma; what are the causes?
Agricultural Health Study
Rusiecki et al, Env Health Perspect 2009
• 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
Agricultural Health Study: myeloma
Rusiecki et al, Env Health Perspect 2009
• 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
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
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
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
• 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
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
NHANES Study
• 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
Summary and conclusions
• Agricultural Health Study: part II (NCI)
• Agent Orange exposed veterans (CDC/VA)
•World Trade Center rescue workers (FDNY/Albert Einstein College of Medicine)
Selected ongoing studies (collaborators)
Thank you for your attention!
Ola Landgren, M.D, Ph.D.Chief, Myeloma Service
Memorial Sloan-Kettering Cancer Center1275 York Avenue, New York, NY 10065, USA
Email: [email protected] Phone: 212-639-5126