NCI’s Division of Cancer Epidemiology and Genetics

Neil Caporaso, M.D.Chief, Genetic Epidemiology Branch

DCEG, NCIwww.dceg.cancer.gov

Division of Cancer Epidemiology and GeneticsDiscovering the Causes of Cancer

national and international intramural, population-based research

Mission:

* broad-based, high quality, high impact research to uncover causes of cancer and means of its prevention.

* national and international perspective.

* develop research resources and strategic partnerships in molecular epidemiology across NCI, NIH and the research global community

* train the next generation of scientists in cancer epidemiology and related areas.

National Cancer Institute

IntramuralDivisions

Extramural Divisions

DCEG CCR

~205 Investigators8 Branches/1 Lab

69 Principal Investigators

National Cancer Institute (NCI)

Division of Cancer Epidemiology and Genetics

Genetic Epidemiology BranchOther Branches focus onNutrition, Hormones, Infection,Occupation, Statistics, Radiation

Find the CAUSE!

Benign monoclonal B-cell lymphocytosis (BMBCL) Han 1984Idiopathic persistent lymphocytosis Bassan 1988B-monoclonal lymphocytosis undetermined significance Garcia 1989Smoldering CLL Montserrat 1988B-cell monoclonal lymphocytosis (BCML) Marti 1993Sub-clinical BCLL B-cell monoclonal lymphocytosis Maiese 1997CD5 negative BMLUSWang 2002

CLL-like immunophenotype (CLUS) Rawstron 2

Why have an intramural program?Example 1

In the 1980/90s many groups independently reportedthat normal patients had excess clonal B lymphocytes in the blood.

Each investigator gave it a different name

2

Why have an intramural program?

2003 2005 2007 2010

Monoclonal B Cell Lymphocytosis (MBL)

Family Studies were not popular

Early ideas in human genetics:

If it’s genetic it’s rareIf its genetic it’s only in familiesIf it’s genetic you can’t change itIf it’s genetic there is no treatmentIf it’s genetic the environment doesn’t matter

ALL THESE ASSUMPTIONS WERE WRONG

Example 2

Family studies by our group…..

Family studies by our group…..

dysplastic nevus

Most Cancer is due to the Environment

Dramatic differences in cancer rates by geography and over time are only compatible with extrinsic environmental causes

Established by a vast body of descriptive, ecological, and analytical epidemiology

Per-Capita Consumption of Different Forms of Tobacco in The U.S. 1880-2003

CigarettesCigars

Pipe/roll your own

Chewing

Snuff

0

2

4

6

8

10

12

14

1880 1890 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000Year

Poun

ds o

f Tob

acco

Per

-Cap

ita

Cigarettes Cigars Pipe/roll your own Chewing Snuff

Data Source USDADecades in the 1900s

Relative Risks of Lung Cancer According to Years Since Quitting Smoking among Males in Three Cohort Studies of Smokers

0

2

4

6

8

10

12

14

16

18

20

0 1-4 5-9 10-14 15-19 20+

Years Since Quitting Smoking

Re

lati

ve

Ris

k

British Physicians U.S. Veterans American Cancer Society

Lung cancer rate drops after smoking cessation

Why here?

Copper Smelter, Montana

Traditional epidemiology

E D

Exposure Disease

Tobacco Lung Cancer

Molecular epidemiology

E DID EBE ASF ED

G

exposure internal dose

early biological effect altered structure or function

early disease disease

Adding biomarkers allows us to investigate

genes and mechanisms

Integrative epidemiology

E DID EBE ASF ED

Outcome

G

B O

Behavior

exposureinternal dose

early biological effect altered structure or function

early disease

disease

• Lifestyle risk factors (hormonal and nutritional exposures)

• Environmental and occupational exposures

• Infectious agents

• Radiation

• Statistics and methods development

• Genetic predisposition

• Genome-wide association studies

and Next-gen sequencing

DCEGAreas of Investigation

~100 postbaccalaureate, predoctoral,

postdoctoral and clinical trainees

~25 summer students

26 tenure-track investigators

43 senior investigators

DCEGStaff and Trainee Profile

36 staff scientist/staff clinicians

DCEGSelected Discoveries

Hormone replacement and breast/ovarian cancer

Benzene and formaldehyde and leukemia/lymphoma

Role of p53 gene in Li-Fraumeni syndrome

Gail breast cancer risk model

Cancer risk among atomic bomb survivors

No link between breast implants – breast cancer, cell phones – brain cancer, or power-lines – childhood leukemia

Personal view- Our Branch

Selected Discoveries (GEB/2014)

Largest study of genes and lung cancer

POT1- gene associated with familial melanoma

Methylome and lung cancer

The “Time to First Cigarette” is a critical determinant of lung cancer risk

DCEGWhat we look for in early career investigators

• Great science: important work, published in top-notch journals

• Good quality work: strong rationale and research methods

• Depth and breath of scientific knowledge

• Evidence of creativity, innovation, and originality – person is moving the field forward

• Collaborative, interdisciplinary spirit

• Capacity for independence and leadership

• Ability and enthusiasm to mentor

Personal viewWhat we look for in early career investigators

3 qualities

TRAINING

MOVIVATION and CHARACTER

HARD WORK