The links between non-Hodgkin's lymphoma and

exposures to pesticides and other environmental agents

Yutaka AokiLynn Goldman

Johns Hopkins School of Public HealthDepartment of Environmental Health Sciences

APHA Annual Meeting, October 24, 2001

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

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?

Trends in USA: 1973-1998

Based on Surveillance, Epidemiology and End Results (SEER) Data

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Trend in age-adjusted annual incidence for NHLTrend in age-adjusted annual incidence for NHLYearYear

19701970 19801980 19901990 2000200000

55

1010

1515

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2525 All Males All Males

All Females All Females

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

NHL Mortality MAP for USA

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

Pesticides• Phenoxy herbicides (2,4-D, 2,4,5-T, etc)

– Dioxin as a contaminant – Among farmers, more exposurehigher 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

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

Swedish human breast milk monitoring results reported by Noren & Meironyte (2000)

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Dioxins PBDE <===== ====>

Polybrominated Diphenyl Ether (PBDE)

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

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

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

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How much of increase is explained by known factors?

• Let’s think of a period of 20 years, 1970-90, 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

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

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

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

NHL Mortality MAP for USA

Use this map when printing in black & white

Contact information and acknowledgement

Yutaka Aoki 615 N. Wolfe Street, Box 1249 Baltimore, MD 21205 email: yaoki@jhsph.edu

This project was funded by Physicians for Social Responsibility.