UCLA

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UCLAs Jonsson Comprehensive Cancer Center
Molecular Epidemiology (Developing)

• Zuo-Feng Zhang, M.D., Ph.D., Director
• Curtis Eckert, Ph.D., Associate Director

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Alper Symposium of Molecular Epidemiology of Lung
and Other Smoking-Related Cancers

• UCLA Department of Epidemiology
• School of Public Health
• April, 14, 2007

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UCLAs Jonsson Comprehensive Cancer Center
Molecular Epidemiology (Developing)

• Program Mission
• To develop a multidisciplinary molecular
  epidemiologic approach using the newly developed
  technologies to understand gene-environment
  interactions that may alter the risk and
  progression of cancer and to apply the knowledge
  to cancer risk assessment (primary prevention),
  early detection (secondary prevention) and
  prognosis prediction (tertiary prevention).
• Scientific Themes
• First theme Primary prevention Environmental
  exposure (smoking, diet, infection, air
  pollution, etc.) and genetic susceptibility-based
  cancer risk assessment and gene-environmental
  interactions on the risk of cancers.
• Second theme Secondary prevention Biological
  markers for early detection and intermediate
  markers as surrogate end-points for
  chemoprevention.
• Third theme Tertiary prevention Blood and
  tissue-based biological markers for cancer
  prognosis prediction.

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UCLAs Jonsson Comprehensive Cancer Center
Molecular Epidemiology (Developing)

• Number of Members 18
• NCI Funding (N9)2.2 M
• Other Federal Peer Reviewed Funding (N22)5.4 M
• Other Funding (N22)4.0 M
• Total Funding11.6 M
• Cancer Publications 123
• Interprogrammatic 17
• Intraprogrammatic 12

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UCLAs Jonsson Comprehensive Cancer Center
Molecular Epidemiology (Developing)

• Platforms for Activities
• Monthly Seminar Series on Molecular Epidemiology,
  Molecular Toxicology, and Genomics and Nutrition.
  Monthly DCPCR Monthly Teas to discuss mutual
  research interests with other programs within
  DCPRC
• Yearly Meeting/Retreats on Molecular
  Epidemiology, Gene-Environment Interaction on
  Cancer. Bi-annual Alper-JCCC Symposium on
  Environmental Genomics and Risk of Cancer

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UCLAs Jonsson Comprehensive Cancer Center
Molecular Epidemiology (Developing)
Susceptibility Markers for Primary Prevention

• We have assayed over 150 genetic polymorphisms of
  genes in the metabolic, inflammatory, cell cycle
  control, DNA repair pathways
• Among 4,000 study subjects with cancers of seven
  sites including lung, head and neck, esophagus,
  stomach, liver, prostate, and bladder,
• Using high through-put genotyping platform ABI
  SNPlex (JCCC Genotyping Core). An additional
  200-300 SNPs will be assayed among 4,000 study
  subjects.

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Diet/nutrient
Free radicals Oxidative Stress
DNA damage repaired
Defected DNA repair gene
If DNA damage not repaired
G0
If loose cell cycle control
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Joint effect of tobacco smoking and XPG
polymorphism on lung cancer risk
Departure from additivity 23-13-1.919.1, 95
CL-2.9, 21.7
Pack-years Never
1-20 gt20
Never
1-20 gt20 XPG
Asp/Asp Asp/Asp
Asp/Asp His/His
His/Asp His/His His/Asp
His/His His/Asp
Cui Y, Morgenstern H, Greenland S, Tashkin DP,
Mao J, Cao W, Cozen W, Mack TM, Zhang ZF.
Polymorphism of Xeroderma Pigmentosum group G and
the risk of lung cancer and squamous cell
carcinomas of the oropharynx, larynx and
esophagus. Int J Cancer. 2006 Feb 1118(3)714-20.
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Joint effect of tobacco, alcohol, and XPG
polymorphism on SCCUAT
Drinks per day 1-2 1-2
gt3 gt3
1-2 1-2
gt3
gt3 Packyears lt20
lt20 lt20 lt20
gt20 gt20
gt20 gt20 XPG
Asp/Asp His/His His/Asp
Asp/Asp His/His His/Asp Asp/Asp
His/His His/Asp Asp/Asp His/His
His/Asp
Cui Y, Morgenstern H, Greenland S, Tashkin DP,
Mao J, Cao W, Cozen W, Mack TM, Zhang ZF.
Polymorphism of Xeroderma Pigmentosum group G and
the risk of lung cancer and squamous cell
carcinomas of the oropharynx, larynx and
esophagus. Int J Cancer. 2006 Feb 1118(3)714-20.
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UCLAs Jonsson Comprehensive Cancer Center
Molecular Epidemiology (Developing)Secondary
Prevention Markers for Early Detection/Chemopreve
ntion

• -Epidemiological study of green tea drinking and
  risk of cancers
• -Gene-green tea interaction on risk of cancers
• -Proteomics approach to identify potential target
  for the effect of green tea, using JCCC
  Proteomics Core.

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Mu LN, Lu QY, Yu SZ, Jiang QW, Cao W, You NC,
Zhou XF, Ding BG, Wang RH, Zhao J, Cai L, Rao JY,
Heber D, Zhang ZF. Green tea and its interactions
with other risk factors on the risk of stomach
cancer in a Chinese population. International
Journal of Cancer 2005 116 972-83.
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Xiao GS, Jin YS, Lu QY, Zhang ZF, Belldegrun A,
Figlin R, Pantuck A, Yen Y, Li F, Rao J.
Annexin-I as a potential target for green tea
extract induced actin remodeling. Int J Cancer.
2007 Jan 1120(1)111-20.
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UCLAs Jonsson Comprehensive Cancer Center
Molecular Epidemiology (Developing) Markers for
Progression

• p53 is an independent predictor of tumor
  recurrence and progression after nephrectomy in
  patients with localized renal cell carcinoma.
  Shvarts O, Seligson D, Lam J, Shi T, Horvath S,
  Figlin R, Belldegrun A, Pantuck AJ. J Urol
  2005173(3)725.
• - Reg IV a promising marker of hormone
  refractory metastatic prostate cancer. Gu Z,
  Rubin MA, Yang Y, Deprimo SE, Zhao H, Horvath S,
  Brooks JD, Loda M, Reiter RE. Clin Cancer Res
  200511(6)2237.
• - Using tumor markers to predict the survival of
  patients with metastatic renal cell carcinoma.
  Kim HL, Seligson D, Liu X, Janzen N, Bui MH, Yu
  H, Shi T, Belldegrun AS, Horvath S, Figlin RA. J
  Urol 2005173(5)1496.
• - Prostate stem cell antigen is overexpressed in
  prostate cancer metastases. Lam JS, Yamashiro J,
  Shintaku IP, Vessella RL, Jenkins RB, Horvath S,
  Said JW, Reiter RE. Clin Cancer Res
  200511(7)2591.
• - Global histone modification patterns predict
  risk of prostate cancer recurrence. Seligson DB,
  Horvath S, Shi T, Yu H, Tze S, Grunstein M,
  Kurdistani SK. Nature 2005435(7046)1262.
• - Tumor classification by tissue microarray
  profiling random forest clustering applied to
  renal cell carcinoma. Shi T, Seligson D,
  Belldegrun AS, Palotie A, Horvath S. Mod Pathol
  200518(4)547.

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Bladder Tissue Array
HE
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Yang YC, Lu ML, Rao JY, Wallerand H, Cai L, Cao
W, Pantuck A, Dalbagni G, Reuter V, Figlin RA,
Belldegrun A, Cordon-Cardo C, Zhang ZF. Joint
association of polymorphism of the FGFR4 gene and
mutation TP53 gene with bladder cancer prognosis.
Br J Cancer. 2006 Dec 495(11)1455-8.
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UCLAs Jonsson Comprehensive Cancer Center
Molecular Epidemiology (Developing)

• Clinical Research
• of Trials N/A
• of High Priority Clinical Trials N/A
• Total of Patient Accruals N/A

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UCLAs Jonsson Comprehensive Cancer Center
Molecular Epidemiology (Developing)

• Role of the Cancer Center
• Space Hankinson, Rao, Zhang
• Funding (Seed, Interdisciplinary) 70k
• Faculty recruitment/retention Liu (Simin)
• Use of shared resources Flow Cytometry, Gene
  Expression, Tissue Procurement, Molecular
  Screening, Genotyping
• indicates listing in two program areas

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UCLAs Jonsson Comprehensive Cancer Center
Molecular Epidemiology (Developing)

• Future Plans and Goals
• -Enhance the molecular epidemiology and
  gene-environment interaction research and
  training.
• -Continue the research into molecular
  epidemiology and gene-environment interaction on
  risk of cancers using cutting-edge technology
• -Foster multidisciplinary approaches and
  collaborations between program faculty.