GRANT TO OPEN CENTERFOR ENVIRONMENTALHEALTH AND SUSCEPTIBILITYAWARDED IN APRIL 2001

How do variations in people’sgenes affect their susceptibility toenvironmental factors such aschemicals and radiation?

How does susceptibility differaccording to age, particularly inearly development?

How do toxins move throughthe body, and why does environ-mental exposure impact somepeople differently than others?

These are the types of ques-tions that a diverse group ofresearchers at the new Center for Environmental Health andSusceptibility (CEHS) at theUNC-Chapel Hill School ofPublic Health are investigatingthrough state-of-the-art environ-mental health research. In April2001, UNC-CH was selected asthe newest site for one of 22 suchcenters funded by the National

Institute of Environmental HealthSciences (NIEHS). This excitingresource for North Carolina aimsto help reduce the burden of environmentally related disease,enhance knowledge about howtoxic chemicals affect humans,and improve our understandingof the environmental and geneticdeterminants of disease in differ-ent populations.

THREE AREAS OF RESEARCH FOCUS

The CEHS, led by Dr. JamesSwenberg, brings together UNC-CH scientists in environ-mental epidemiology, environ-mental health and environmentaltoxicology to concentrate onresearch in three core areas thatcan affect the likelihood of a person developing disease fromexposure to hazardous materials: 1. Genetic susceptibility,

or how variation in people’sgenes changes their suscepti-bility to environmental

The CEHS brings together UNC-CH scientists in environmental epidemiology, health, and toxicology.

The Center for Environmental Health and Susceptibility at the University of North Carolina, Chapel Hill Spring 2002, Issue #1

S E N T I N E LUNC Chosen for Innova t i veNat iona l Research Center

Visit the

UNC-Chapel Hill

Center for

Environmental Health

and Susceptibility’s

website at

www.sph.unc.edu/cehs/

for more information on

research taking place at

the CEHS.

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factors such as chemicals orradiation, and lifestyle choic-es like diet and smoking. Inthis core, researchers focuson molecular epidemiology,DNA damage and repair, andgene-environment interaction,to address possible healtheffects such as cancer, repro-duction and developmentalproblems, and neurologic andcardiovascular disease.

2. Developmental susceptibili-ty, or increased vulnerabilityto toxic agents during earlystages of life. This corefocuses on the health effectsof environmental exposurefrom the time of conceptionthrough childhood and exam-ines health impacts such aspregnancy loss, birth defects,developmental deficits andchildhood cancer. Laboratoryresearchers and epidemiolo-gists are also looking at pater-nal and maternal influences

on susceptibility to environ-mental exposure.

3. Toxicokinetic susceptibility,which focuses on understand-ing how chemicals movethrough and are processed bythe human body, and whysome people react differentlyto these toxins than others.The CEHS researchers arelooking at differences amongindividuals and across speciesto determine the effects ofchemicals on human healthand give us more accurateassessments of health risks. The Center’s research in

each of these areas is supportedby four Facility Cores led byUNC-CH faculty who specializein high-throughput genotyping,biostatistics and epidemiologicalmethods, biomarkers, and nutri-ent assessment — expertise that is essential to this type ofcutting-edge investigation. The CEHS also includes a

community outreach and educa-tion program and pilot projectsthat encourage promising new collaborative research.

CONNECTING THECENTER’S WORK TOTHE COMMUNITY

A key component of theUNC-CH CEHS is theCommunity Outreach andEducation Program (COEP). The COEP designs and imple-ments programs to: • Communicate the Center’s

research findings to a broadaudience so this knowledgecan be used to improve publichealth programs and policy,

• Educate the public about howindividual and group suscep-tibilities interact with envi-ronmental and occupationalfactors to cause disease, and

• Foster collaboration betweenCenter scientists and commu-nity groups in order toinvolve community membersin the research process to the maximum extent possible.The COEP, which benefits

from the community outreachand education expertise of UNC-CH’s EnvironmentalResource Program (ERP), sponsors a range of activities to ensure that the Center’sresearch taking place is widelyunderstood by North Carolinacommunity organizations, teachers, students, public healthofficials and businesses. TheCOEP’s activities include:• Collaboration with communi-

ty groups, state governmentofficials, and Center scientists to guide the

The new UNC Center is directed by Jim Swenberg (left) with assistancefrom Jorge Izquierdo (right), the Center’s Scientific Coordinator.

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CEHS’s efforts to share its research findings with the public and build commu-nity-academic partnerships to facilitate communityinvolvement in researchopportunities.

• A community-focused under-graduate internship program to give Carolina studentshands-on experience in thefield of environmental healthand susceptibility.

• Professional development programs for North CarolinaK–12 educators to enhancetheir ability to teach studentsabout susceptibilities and theenvironmental and occupa-tional aspects of health.

• A new website and thisSentinel newsletter to share the Center’s important workand its research findings witha broad audience.The COEP has already

engaged UNC-CH scientists andNorth Carolina citizens in focusgroups to examine incentivesand barriers to working togetherto achieve the CEHS’s goals, and surveyed NC teachers todetermine topics of interest forprofessional development pro-grams that draw on the CEHS’sresearch strengths. In addition,the Center has collaborated witha low-income community to col-lect data on local air pollution.As highlighted in the followingarticle, the COEP has also begun a project to develop, pilot and disseminate educational materi-als for lay audiences to examinethe ethical, legal, and socialissues involved in research ongene-environment interactions. ■

CEHS Wins Two NewResearch Grants

WITHIN JUST A FEW months of its creation, theUNC-CH CEHS was awardedthe following two researchgrants from the NationalInstitutes of Health.

UNDERSTANDING THEGENETICS OF TOXIN-INDUCED CANCER

The first is a five-year, $7 million-plus grant to helpdefine how individual genesinfluence a person’s risk ofdeveloping cancer as a result ofexposure to toxins in the envi-ronment. CEHS researcherswith expertise in toxicology,genomics and DNA repair areusing powerful gene-focusedtechnology to examine thereaction of 10,000 to 20,000

different genes in humans andmice when they are exposed toenvironmental toxic agents.

Dr. William K. Kaufmann,Director of the Center’s GeneticSusceptibility Research Coreand Professor of Pathology andLaboratory Medicine in theSchool of Medicine, is the prin-cipal investigator for the UNC-CH team. “Lots of things thatpeople are exposed to in every-day life contain mixtures of toxins, including car exhaust,cigarette smoke, air pollutionand contaminated water,” heexplains. “While some of theseenvironmental toxins mightinfluence a person’s risk ofdeveloping cancer, others mightnot. Furthermore, two peoplecan be exposed to the same

Dr. William Kaufmann (left), Director of the Center’s Genetic SusceptibilityResearch Core, consults with Charles Perou, Assistant Director of theToxicogenomics Program.

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researchers are examining themechanisms that control thedivision of cells to learn howthat process is altered by damageto genes. This knowledge will be applied to determine whetherpeople with breast cancer dis-play defects in the normal pat-tern of response that increasestheir risk of developing addition-al mutations. ■

toxins, but one might developcancer while the other doesn’t.”

“Through this research project, we hope to determinewhy some known gene muta-tions enhance a person’s risk of developing cancer whenexposed to environmental car-cinogens, to discover new genemutations that enhance risk, and to determine if genetic dif-ferences can help explain whysome people seem predisposedtoward cancer development after low-level toxin exposurewhile many others are not.” Tounderstand how environmentaltoxic agents cause cancer andproduce adverse effects onhuman health, researchers useinbred and genetically engi-neered mice as animal models.

This grant is part of a larger$37 million effort that includesfour other academic researchorganizations and is headed by the NIEHS. The UNC-CHteam is a collaboration betweenthe CEHS and the LinebergerComprehensive Cancer Center.

FURTHERINGENVIRONMENTALEDUCATION AND RESEARCHA $150,000 GRANT FROMthe NIEHS is funding two programs at the Center. The first component of the grant is to educate the public on ethical,legal and social issues related to environmental genomics.Funding will allow the Center to develop educational moduleson gene-environment risk factorsfor breast cancer and on the risksfrom gene-toxin interactions in

the workplace. The Center’sCOEP will develop and pilotthese modules with two commu-nity partners, the North CarolinaBreast Cancer Coalition and theNorth Carolina OccupationalSafety and Health Project, andwill ultimately disseminate these materials nationally. In Fall 2001, an interdisciplinaryScientific Advisory Board met tohelp develop these educationalmaterials. UNC-CH is also col-laborating with the COEPat the University of Cincinnation this project.

The second component of thegrant, led by Bill Kaufmann, isfor an interdisciplinary researchproject to determine how the riskof developing breast cancer isaffected by the body’s ability torepair DNA damage caused byenvironmental factors. CEHS

UNC-CH senior Lindsay Kim (far right) analyzed federal data about

air quality in Moncure, NC, and presented her findings to the commu-

nity. Also pictured are (left to right) Valencia Deans, an NC State

University senior, Ellen Pietroski of NC Waste Awareness and

Reduction Network, and Harold Taylor, a lifelong resident and commu-

nity activist.

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DR. ANDREW OLSHAN Professor of Epdemiology,directs the Center’sDevelopmental SusceptibilityResearch Core, which focuses on the effect of environmentalexposures from conceptionthrough childhood. He also is a member of the GeneticSusceptibility Research Core.Here are research projects he is working on through the CEHS.

ENVIRONMENTAL AND GENETIC RISKFACTORS FORCHILDHOOD CANCER

On the heels of a nationalstudy of neuroblastoma, a child-hood nervous system tumor,Olshan is now conducting a five-year study of Wilms tumor,a rare childhood kidney tumor.Working through a national clinical trials network, he plansto identify about 800 cases of Wilms across the country. As in the first study, he will

Beh ind the Scenes : A Glance in to theResearch o f Ep idemio log i s t Andrew Olshan

Dr Andrew Olshan, Director of theCenter’s Developmental SusceptibilityResearch Core, is collaborating with scientists from other fields to study environmental and genetic risk factors in cancer.

“The Center has opened up newopportunities to learn about what

other researchers are doing and hasfacilitated collaboration that may

not have existed before.”— Epidemiologist Andrew Olshan

THE EFFECT OFDRINKING WATER ON MALEREPRODUCTIVE HEALTH

Building on a national studyby fellow CEHS researcher Dr. David Savitz of possiblelinks between the byproducts of drinking water disinfectionand the risk of miscarriage,Olshan is partnering with theEnvironmental ProtectionAgency (EPA) to investigate the impact of these byproductson male reproductive health. He is working with EPA repro-ductive toxicologist Dr. SallyDarney, an affiliate member of the Center’s DevelopmentalSusceptibility Core, to interviewand collect semen samples fromthe male partners of the womenin Savitz’s study. “There is evi-dence in animals that these

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interview the parents of thesechildren, and a control group of parents whose children don’thave cancer, about their expo-sures to chemicals at home and in the workplace, lifestylefactors and medical history. In collaboration with theCenter’s Genetic SusceptibilityResearch Core, he also hopes to collect DNA samples from the parents and children toexplore genetic factors that mayimpact the risk of developingchildhood cancers when pairedwith certain toxic exposures.

“The fact that these particularcancers are diagnosed within the first four years of life pointsto a relatively small critical win-dow of exposure. This gives us an excellent situation to studyhow cancer develops in thesechildren, including exploring the parents’ exposures to envi-ronmental risk factors around the time of conception and the mother’s exposures duringpregnancy.”

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byproducts in drinking waterhave a stronger effect on repro-duction in males than in females,resulting in lower sperm countand higher prevalence of spermabnormalities, for example.Adding on to Savitz’s nationalstudy gives us a unique and efficient opportunity to explorethese issues in men.”

GENETIC LINKS TO HEAD AND NECK CANCER

Olshan’s biggest study crosses boundaries among theCenter’s research cores, creatingopportunities for collaborationwith scientists specializing ingenetic susceptibility, genotypingand DNA damage and repair. Hehas received funding from theNational Cancer Institute for afive-year study to understand

how a person’s genetic make-upinteracts with the risk factorsfor head and neck cancer —smoking and alcohol consump-tion — to determine whetherthis type of cancer develops ornot. Olshan plans to study about1,500 cases of head and neckcancer in North Carolina. Thisis the largest study of its kind in the country. “Why can somepeople drink or smoke all theirlives and not get cancer, whileothers do? We want to know the genetic factors that modifytheir risk. Head and neck canceris an excellent model because we know what the risky behav-iors are, so we can look atgenetic factors that may beinvolved in metabolizing tobac-co and alcohol and repairing the damage to DNA caused bysmoking or drinking.” ■

S E N T I N E LThis newsletter is published annually

by the Center for Environmental Healthand Susceptibility at the University ofNorth Carolina at Chapel Hill, with

funding from the National Institute ofEnvironmental Health Sciences.

James A. SwenbergCenter Director919-966-6139

james_swenberg@unc.edu

Frances LynnCOEP Director919-966-3335

fran_lynn@unc.edu

S E N T I N E LLaura Ertel and Outreach Staff,

WritersRegina McCoy-Hopper,

Design and layout, CHAI Core, funded by the ClinicalNutrition Research Center and the Nutrient Assessment Facility Core

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