Skip Navigation
National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R29CA070334-05 Interpret this number
Primary Investigator: Wei, Qingyi
Organization: University Of Texas Md Anderson Can Ctr
Project Title: Molecular Epidemiology of DNA Repair in Melanoma
Fiscal Year: 2000
Back to top


Abstract

Although sunlight exposure has been implicated in risk of cutaneous malignant melanoma (CMM), the exact role of ultraviolet light (UV in the etiology of CMM remains unclear. Host susceptibility to UV damage may also play an important role. Based on the high frequency of melanoma and other a skin cancer in xeroderma pigmentosum patients, we hypothesize that cellular DNA repair plays a role in the etiology of UV-induced human melanoma. This hypothesis is supported by the finding of our pilot studies that lymphocytes from melanoma patients tend to have low capacity to repair UV-induced DNA damage. To test this hypothesis, we propose to conduct a molecular epidemiologic study of melanoma using a case-control study design to measure the DNA repair capacity in peripheral lymphocytes. Three hundred untreated melanoma cases and 300 age-and-sex-matched controls without cancer will be included in this steady. A self-administered risk- factor questionnaire will be used for data collection and a 30-ml blood sample drawn for laboratory assays for each subject. The data analysis will emphasize sunlight exposure and age stratification, which will integrate with DNA repair capacity to evaluate genetic susceptibility to CMM. Logistic regression analysis will be used to adjust for possible confounding effects of other known risk factors such as family history of CMM, skin type, and skin lesions including dysplastic nevi. A subset of 200 subjects based on their DNA repair capacities measured will be also assayed for UN-induced in vitro mutagen sensitivity for the levels of expression of four DNA repair genes (XPOC, hMSH2, XRCC1, and ERCC1). This approach will allow us to explore the complementary use of these assays in identifying individuals at high risk of CMM. Our specific aims are: (1) to construct detailed epidemiologic and clinical profiles of CMM cases and controls; (2) to determine the association between cellular DNA repair capacity for UV damage and the risk of CMM by using a case-control study design; (3) to study in vitro UV-induced sensitivity and expression of DNA repair genes in a subset of cases and controls expressing high and low repair capacity; and (4) to evaluate the relationship of DNA repair capacity, UV-induced chromosome sensitivity, and DNA-repair gene expression to epidemiologic and clinical data on CMM. This study will help us understand host susceptibility, particularly the role of DNA repair, in the etiology of CMM. The long-term goal of this study is to identify susceptibility markers for the assessment of CMM risk and to identify individuals at high risk of CMM for future cancer-prevention programs.

Back to top


Publications

Reduced Expression Of Mismatch Repair Genes Measured By Multiplex Reverse Transcription-polymerase Chain Reaction In Human Gliomas
Authors: Wei Q. , Bondy M.L. , Mao L. , Gaun Y. , Cheng L. , Cunningham J. , Fan Y. , Bruner J.M. , Yung W.K. , Levin V.A. , et al. .
Source: Cancer Research, 1997-05-01 00:00:00.0; 57(9), p. 1673-7.
PMID: 9135006
Related Citations

Expression Of Five Selected Human Mismatch Repair Genes Simultaneously Detected In Normal And Cancer Cell Lines By A Nonradioactive Multiplex Reverse Transcription-polymerase Chain Reaction
Authors: Wei Q. , Guan Y. , Cheng L. , Radinsky R. , Bar-Eli M. , Tsan R. , Li L. , Legerski R.J. .
Source: Pathobiology : Journal Of Immunopathology, Molecular And Cellular Biology, 1997; 65(6), p. 293-300.
PMID: 9491849
Related Citations

Reduced Expression Of Mismatch Repair Genes In Colorectal Cancer Patients In Egypt
Authors: Soliman A.S. , Bondy M.L. , Guan Y. , El-Badawi S. , Mokhtar N. , Bayomi S. , Raouf A.A. , Ismail S. , McPherson R.S. , Abdel-Hakim T.F. , et al. .
Source: International Journal Of Oncology, 1998 Jun; 12(6), p. 1315-9.
PMID: 9592192
Related Citations

Effect Of Aging On Dna Repair And Skin Carcinogenesis: A Minireview Of Population-based Studies
Authors: Wei Q. .
Source: The Journal Of Investigative Dermatology. Symposium Proceedings / The Society For Investigative Dermatology, Inc. [and] European Society For Dermatological Research, 1998 Aug; 3(1), p. 19-22.
PMID: 9732052
Related Citations

Combined Effect Of Chemopreventive Agent N-(4-hydroxyphenyl) Retinamide (4-hpr) And Gamma-radiation On Bladder Cancer Cell Lines
Authors: Zou C. , Wang L. , Liebert M. , Grossman H.B. , Lotan R. , Wei Q. .
Source: International Journal Of Oncology, 1998 Nov; 13(5), p. 1037-41.
PMID: 9772297
Related Citations

Glutathione-s-transferase Polymorphisms And Risk Of Squamous-cell Carcinoma Of The Head And Neck
Authors: Cheng L. , Sturgis E.M. , Eicher S.A. , Char D. , Spitz M.R. , Wei Q. .
Source: International Journal Of Cancer, 1999-06-21 00:00:00.0; 84(3), p. 220-4.
PMID: 10371337
Related Citations

Expression In Normal Human Tissues Of Five Nucleotide Excision Repair Genes Measured Simultaneously By Multiplex Reverse Transcription-polymerase Chain Reaction
Authors: Cheng L. , Guan Y. , Li L. , Legerski R.J. , Einspahr J. , Bangert J. , Alberts D.S. , Wei Q. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 1999 Sep; 8(9), p. 801-7.
PMID: 10498399
Related Citations

Epidemiologic Determinants Of Clinically Relevant Prostate Cancer
Authors: Spitz M.R. , Strom S.S. , Yamamura Y. , Troncoso P. , Babaian R.J. , Scardino P.T. , Wheeler T. , Amos C.I. , von Eschenbach A. , Kagan J. .
Source: International Journal Of Cancer, 2000-05-20 00:00:00.0; 89(3), p. 259-64.
PMID: 10861502
Related Citations

Dna Repair Capacity In Healthy Medical Students During And After Exam Stress
Authors: Cohen L. , Marshall G.D. , Cheng L. , Agarwal S.K. , Wei Q. .
Source: Journal Of Behavioral Medicine, 2000 Dec; 23(6), p. 531-44.
PMID: 11199086
Related Citations

An Intronic Poly (at) Polymorphism Of The Dna Repair Gene Xpc And Risk Of Squamous Cell Carcinoma Of The Head And Neck: A Case-control Study
Authors: Shen H. , Sturgis E.M. , Khan S.G. , Qiao Y. , Shahlavi T. , Eicher S.A. , Xu Y. , Wang X. , Strom S.S. , Spitz M.R. , et al. .
Source: Cancer Research, 2001-04-15 00:00:00.0; 61(8), p. 3321-5.
PMID: 11309287
Related Citations

Gamma-radiation Sensitivity And Risk Of Glioma
Authors: Bondy M.L. , Wang L.E. , El-Zein R. , de Andrade M. , Selvan M.S. , Bruner J.M. , Levin V.A. , Alfred Yung W.K. , Adatto P. , Wei Q. .
Source: Journal Of The National Cancer Institute, 2001-10-17 00:00:00.0; 93(20), p. 1553-7.
PMID: 11604478
Related Citations

N-(4-hydroxyphenyl)retinamide (4-hpr) Modulates Gadd45 Expression In Radiosensitive Bladder Cancer Cell Lines
Authors: Zou C. , Guan Y. , Zou C. , Wang J. , Wang L.E. , Liebert M. , Grossman H.B. , Wei Q. .
Source: Cancer Letters, 2002-06-28 00:00:00.0; 180(2), p. 131-7.
PMID: 12175543
Related Citations