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
•
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: abnormal plasma
cells in the bone marrow
Multiple myeloma: lytic bone lesions
Hillengass and Landgren. Leuk Lymphoma 2013
Multiple myeloma: genetic
heterogeneity within each patient
Lohr et al. Cancer Cell 2014
Multiple
myeloma
and its
precursor
“MGUS”
Cumulative risk (%) of myeloma
“Monoclonal gammopathy of
undetermined significance” (MGUS)
Risk of
developing
multiple
myeloma
(0.5-1%
per year)
Year of follow-up
Kyle, Am J Med 1978; Turesson et al. Blood 2014
Myeloma consistently preceded by
precursor state “MGUS”
>77,000 cancer free men
and women; stored
annual blood tests
Up to 10 years of follow-up
Landgren et al. Blood 2009
Multiple
myeloma
(n=71)
Risk factors
for multiple
myeloma;
what are the
causes?
Risk factors for multiple myeloma;
what are the causes?
•
•
•
•
•
•
Older age
Male gender
Family history of myeloma
African American descent
Obesity
Farming/pesticides
Rusiecki et al, Env Health Perspect 2009
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
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
Agricultural Health Study: MGUS
Landgren et al, Blood 2009
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 carbontetrachloride/carbon disulfide, and the fungicide
chlorothalonil
• These findings support hypothesis that specific
pesticides causatively linked to myelomagenesis
Landgren et al, Blood 2009
National Health and Nutritional
Examination Survey (NHANES)
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
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
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
Summary and conclusions
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
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)
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