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NCI’s Division of Cancer
Epidemiology and Genetics
Neil Caporaso, M.D.
Chief, Genetic Epidemiology Branch
DCEG, NCI
www.dceg.cancer.gov
Division of Cancer Epidemiology and Genetics
Discovering 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
Intramural
Divisions
DCEG
8 Branches/1 Lab
69 Principal
Investigators
Extramural
Divisions
CCR
~205 Investigators
National Cancer Institute (NCI)
Division of Cancer Epidemiology and Genetics
Find the CAUSE!
Genetic Epidemiology Branch
Other Branches focus on
Nutrition, Hormones, Infection,
Occupation, Statistics, Radiation
Why have an intramural program?
Example 1
In the 1980/90s many groups independently reported
that normal patients had excess clonal B
lymphocytes in the blood.
Each investigator gave it a different name
Benign monoclonal B-cell lymphocytosis (BMBCL)
Idiopathic persistent lymphocytosis
B-monoclonal lymphocytosis undetermined significance
Smoldering CLL
B-cell monoclonal lymphocytosis (BCML)
Sub-clinical BCLL B-cell monoclonal lymphocytosis
CD5 negative BMLUS
CLL-like immunophenotype (CLUS)
Han 1984
Bassan 1988
Garcia 1989
Montserrat 1988
Marti 1993
Maiese 1997
Wang 2002
Rawstron 2
Why have an intramural program?
2
2003
2005
2007
2010
Monoclonal B Cell Lymphocytosis (MBL)
Example 2
Family Studies were not popular
Early ideas in human genetics:
If it’s genetic it’s rare
If its genetic it’s only in families
If it’s genetic you can’t change it
If it’s genetic there is no treatment
If it’s genetic the environment doesn’t matter
ALL THESE ASSUMPTIONS WERE WRONG
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
Pounds of Tobacco Per-Capita
14
Cigarettes Cigars Pipe/roll your own Chewing Snuff
12
10
8
6
4
Snuff
Chewing
Pipe/roll
your own
Cigarettes
Cigars
2
0
1880 1890 1900 1910 Decades
1920 1930
in the1940
1900s1950 1960 1970 1980 1990 2000
Year
Data Source USDA
Lung cancer rate drops after smoking cessation
Relative Risks of Lung Cancer According to Years Since Quitting Smoking
among Males in Three Cohort Studies of Smokers
20
18
16
Relative Risk
14
12
10
8
6
4
2
0
0
1-4
5-9
10-14
15-19
Years Since Quitting Smoking
British Physicians
U.S. Veterans
American Cancer Society
20+
Why here?
Copper Smelter, Montana
Traditional epidemiology
E
Exposure
Tobacco
D
Disease
Lung Cancer
Molecular epidemiology
G
E
exposure
ID
EBE
ASF
ED
D
internal dose
early biological effect
altered structure or function
early disease
disease
Adding biomarkers allows us to investigate
genes and mechanisms
Integrative epidemiology
G
B
E
ID
EBE
ASF
ED
D
O
exposure
internal dose
early biological effect
altered structure or function
early disease
disease
Behavior
Outcome
DCEG
Areas of Investigation
• 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
DCEG
Staff and Trainee Profile
~25 summer students
~100 postbaccalaureate, predoctoral,
postdoctoral and clinical trainees
36 staff scientist/staff clinicians
26 tenure-track investigators
43 senior investigators
DCEG
Selected 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
DCEG
What 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 view
What we look for in early career investigators
3 qualities
TRAINING
MOVIVATION and CHARACTER
HARD WORK