1. The links between non-Hodgkin's lymphoma and exposures to pesticides and other environmental agents
Yutaka Aoki
Lynn Goldman
Johns Hopkins School of Public Health
Department of Environmental Health Sciences
APHA Annual Meeting, October 24, 2001

2. Non-Hodgkin’s Lymphoma (NHL) What is it and why bother?
A group of cancers arising in lymph system
Distinguished from Hodgkin’s Disease (HD)
Treatments limited
NHL incidence is rising
Need to control the rise in incidence
Emerging knowledge on environmental exposures as risk factor

3. Non-Hodgkin’s Lymphoma (NHL) Foci of this presentation
A group of cancers arising in lymph system
Distinguished from Hodgkin’s Disease (HD)
Treatments limited
NHL incidence is rising
Need to control the rise in incidence
Emerging knowledge on environmental exposures as risk factor
What should we do?

4. Trends in USA:
Based on Surveillance, Epidemiology and End Results (SEER) Data

5. Clues for the Causes of the Rise
Similar increasing pattern (3~4% annual increase) all over world
The rise is real, i.e., can not be attributed solely to artifact of
Increased detection
Change in classification
Only a part of increase is due to HIV
Incidence higher in developed areas, e.g., USA and Europe

6. NHL Mortality MAP for USA

7. Farming-related Exposures
Higher incidence for Midwest states
Farming as occupation increases risk (RR of 1.1 in a meta-analysis)
Farming is related to exposure to various agents
Pesticides
Hay/Dust
Diesel exhaust
Sunlight
Zoonotic viruses
Healthy life style, etc

8. Pesticides Phenoxy herbicides (2,4-D, 2,4,5-T, etc)
Dioxin as a contaminant
Among farmers, more exposurehigher risk
RR=2.6 in manufacturing workers
Agent orange (largely negative)
Organochlorine insecticides
Chlordane remains to be a suspect
DDT & lindane unlikely
Organophosphate & carbamate insecticides
Use increased after organochlorine regulations

9. Other Persistent Chemicals
PCB
mixed results w/ a positive result from a nested case-control study
PBB (high risk seen in Michigan study)
Dioxins (Manufacturing workers, Seveso)
Polybrominated Diphenyl Ether (PBDE)
Used as flame retardant for plastics and fabrics
One positive study from Sweden

10. Polybrominated Diphenyl Ether (PBDE)
Swedish human breast milk monitoring results reported by Noren & Meironyte (2000)

11. Other Environmental Exposures
Nitrate in groundwater
Connection with use of fertilizer
Mixed results
Solvents (mixed results)
trichloroethylene, tetrachloroethylene, benzene (controversial), other solvents, painter as occupation
Wood dusts & wood-related work
Potential roles of chlorinated phenol wood preservatives

12. Other aspects of suspected or known risk factors
Disruption of immune system confer high risk
HIV(RR~200)
Immunosuppressive therapies (RR~50)
Suspected chemicals such as organophosphates and carbamates are immunotoxic
Some agents found in occupational setting as well as in non-occupational setting with increasing use, e.g.,
Persistent chemicals in diet
Herbicides for crops and lawn
Solvents

13. Contribution of genetic factors
Gene pool is stable over a few decades
Contribution of genetically inherited factors, that act alone, is negligible (Scandinavian twin study)
Possibility for synergetic gene-environment interaction
Polymorphisms in metabolic enzymes may be important as found in childhood leukemia

14. How much of increase is explained by known factors?
Let’s think of a period of 20 years, , with doubling of incidence
A factor solely responsible for the increase
would explain 50% of incidence in 1990; and
should have become more common over time
No such factors found 20
Annual Incidence
(1/100,000) 10
1970
1990
Year

15. How much of increase is explained by known factors? (cont’d)
Each of environmental factors studied accounts only 5~10 % of the risk in each study
Combined effects not thoroughly assessed yet
In a single study, not all of them considered
Exposure trend unknown, e.g., for PBDE
Prevalence of some factors has decreased, e.g., farming
General consensus: the known/suspected factors can explain only a part of increase

16. Policy issues “Epidemic” detected Policy development
Identify and reduce causal exposure
 FURTHER SEARCH FOR CAUSES
Once policies implemented  Assessment
Have we been successful in reducing exposures?
Have we been successful in preventing disease?
Need to “track” changes
 PREPARE FOR FUTURE ASSESSMENT

17. Conclusions
Causes of NHL remain elusive with some promising leads regarding roles of environmental exposures
For sound policy development and assessment, we should
Continue further search for causes and
Keep improving disease and exposure tracking, especially exposure tracking

18. NHL Mortality MAP for USA
Use this map when printing in black & white

19. Contact information and acknowledgement
Yutaka Aoki
615 N. Wolfe Street, Box 1249
Baltimore, MD 21205
This project was funded by Physicians for Social Responsibility.