Skip to main content

COVID-19 Resources

What people with cancer should know: https://www.cancer.gov/coronavirus

Guidance for cancer researchers: https://www.cancer.gov/coronavirus-researchers

Get the latest public health information from CDC: https://www.cdc.gov/coronavirus

Get the latest research information from NIH: https://www.covid19.nih.gov

Grant Details

Grant Number: 5R01CA114665-04 Interpret this number
Primary Investigator: Pike, Malcolm
Organization: University Of Southern California
Project Title: Genetic & Environmental Risk Factors for Bladder Cancer
Fiscal Year: 2009


Abstract

DESCRIPTION (provided by applicant): Occupational exposure to arylamines used in the manufacturing of industrial dyes was the first known cause of human bladder cancer. These carcinogenic arylamines, specifically, 4-aminobiphenyl (4-ABP), beta-naphthylamine, and benzidine, are also contained in tobacco smoke, and are the most likely causative agents responsible for the raised rates of bladder cancer in smokers. Oxidation of arylamines is recognized as a critical first step in turning these chemical species into their carcinogenic metabolites capable of causing DNA damage to urothelial cells. Hair dyes represent another substantial source of arylamines in humans, and we recently showed that sustained use of permanent hair dyes in women is a risk factor for bladder cancer, especially among those deficient in arylamine detoxifying enzymes. Subsequently, 4-ABP was detected in bottles of commercial hair dyes bought in a US store. Then, using hemoglobin adducts of 4-ABP as a biomarker of exposure, we showed that other, presumably diffuse, sources of 4-ABP exposure may be related to bladder cancer in nonsmokers. Thus, the latest evidence indicates arylamine exposure as the primary cause of bladder cancer in the United States. Ten years ago, we reported that a reason for the 3-fold increased risk of bladder cancer in US white versus Chinese men despite their comparable smoking habits may be the higher prevalence in the former population of individuals with deficient arylamine-detoxifying enzymes, which are under genetic control. We capitalized on this finding and launched a population-based case-control study involving both a Los Angeles and a Shanghai, China component to explore genetic factors that play a major role in determining bladder cancer risk in arylamine-exposed individuals. This already completed database consists of roughly 1300 cases of incident bladder cancer (750 cases in Los Angeles, 550 cases in Shanghai) and about an equal number of control subjects. Our initial goals were to investigate the roles of selected polymorphic, arylarnine-metabolizing genotypes/phenotypes in bladder cancer, and in the Los Angeles component, to use hemoglobin adducts as biomarkers of exposure to arylamines in examining nonsmoking-related bladder cancer. In this application, we aim for a more comprehensive understanding of the arylamine-bladder cancer etiologic link through the following extensions on our Los Angeles/Shanghai database: (1) Completion of arylamine hemoglobin adduct measurements on Shanghai subjects in order to compare the respective effects of these adducts on risk between Los Angles and Shanghai study subjects; (2) Addition of genotypes involved in arylamine metabolism, in cellular response to oxidative stress and in DNA repair; and (3) Development of a Bayesian hierarchical statistical model to allow for an efficient, pathway-driven examination of multiple gene-arylamine interactions in bladder cancer. The ultimate goal of this research is to assess individual bladder cancer risk for the purpose of preventive interventions.



Publications

The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease.
Authors: Fu Y.P. , Kohaar I. , Moore L.E. , Lenz P. , Figueroa J.D. , Tang W. , Porter-Gill P. , Chatterjee N. , Scott-Johnson A. , Garcia-Closas M. , et al. .
Source: Cancer research, 2014-10-15; 74(20), p. 5808-18.
PMID: 25320178
Related Citations

Genome-wide interaction study of smoking and bladder cancer risk.
Authors: Figueroa J.D. , Han S.S. , Garcia-Closas M. , Baris D. , Jacobs E.J. , Kogevinas M. , Schwenn M. , Malats N. , Johnson A. , Purdue M.P. , et al. .
Source: Carcinogenesis, 2014 Aug; 35(8), p. 1737-44.
EPub date: 2014-03-24.
PMID: 24662972
Related Citations

Comprehensive analyses of DNA repair pathways, smoking and bladder cancer risk in Los Angeles and Shanghai.
Authors: Corral R. , Lewinger J.P. , Van Den Berg D. , Joshi A.D. , Yuan J.M. , Gago-Dominguez M. , Cortessis V.K. , Pike M.C. , Conti D.V. , Thomas D.C. , et al. .
Source: International journal of cancer, 2014-07-15; 135(2), p. 335-47.
EPub date: 2014-01-13.
PMID: 24382701
Related Citations

Genome-wide association study identifies multiple loci associated with bladder cancer risk.
Authors: Figueroa J.D. , Ye Y. , Siddiq A. , Garcia-Closas M. , Chatterjee N. , Prokunina-Olsson L. , Cortessis V.K. , Kooperberg C. , Cussenot O. , Benhamou S. , et al. .
Source: Human molecular genetics, 2014-03-01; 23(5), p. 1387-98.
EPub date: 2013-10-24.
PMID: 24163127
Related Citations

Dietary sources of N-nitroso compounds and bladder cancer risk: findings from the Los Angeles bladder cancer study.
Authors: Catsburg C.E. , Gago-Dominguez M. , Yuan J.M. , Castelao J.E. , Cortessis V.K. , Pike M.C. , Stern M.C. .
Source: International journal of cancer, 2014-01-01; 134(1), p. 125-35.
EPub date: 2013-07-15.
PMID: 23775870
Related Citations

Elevated 4-aminobiphenyl and 2,6-dimethylaniline hemoglobin adducts and increased risk of bladder cancer among lifelong nonsmokers--The Shanghai Bladder Cancer Study.
Authors: Tao L. , Day B.W. , Hu B. , Xiang Y.B. , Wang R. , Stern M.C. , Gago-Dominguez M. , Cortessis V.K. , Conti D.V. , Van Den Berg D. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2013 May; 22(5), p. 937-45.
EPub date: 2013-03-28.
PMID: 23539508
Related Citations

Cigarette smoking and subtypes of bladder cancer.
Authors: Jiang X. , Castelao J.E. , Yuan J.M. , Stern M.C. , Conti D.V. , Cortessis V.K. , Pike M.C. , Gago-Dominguez M. .
Source: International journal of cancer, 2012-02-15; 130(4), p. 896-901.
EPub date: 2011-05-09.
PMID: 21412765
Related Citations

Lower risk in parous women suggests that hormonal factors are important in bladder cancer etiology.
Authors: Davis-Dao C.A. , Henderson K.D. , Sullivan-Halley J. , Ma H. , West D. , Xiang Y.B. , Gago-Dominguez M. , Stern M.C. , Castelao J.E. , Conti D.V. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011 Jun; 20(6), p. 1156-70.
EPub date: 2011-04-14.
PMID: 21493870
Related Citations

Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study.
Authors: Gago-Dominguez M. , Jiang X. , Conti D.V. , Castelao J.E. , Stern M.C. , Cortessis V.K. , Pike M.C. , Xiang Y.B. , Gao Y.T. , Yuan J.M. , et al. .
Source: Carcinogenesis, 2011 Feb; 32(2), p. 197-202.
EPub date: 2010-11-15.
PMID: 21081471
Related Citations

Risk of urinary bladder cancer is associated with 8q24 variant rs9642880[T] in multiple racial/ethnic groups: results from the Los Angeles-Shanghai case-control study.
Authors: Cortessis V.K. , Yuan J.M. , Van Den Berg D. , Jiang X. , Gago-Dominguez M. , Stern M.C. , Castelao J.E. , Xiang Y.B. , Gao Y.T. , Pike M.C. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010 Dec; 19(12), p. 3150-6.
EPub date: 2010-10-11.
PMID: 21051319
Related Citations

Hypertension, diuretics and antihypertensives in relation to bladder cancer.
Authors: Jiang X. , Castelao J.E. , Yuan J.M. , Groshen S. , Stern M.C. , Conti D.V. , Cortessis V.K. , Coetzee G.A. , Pike M.C. , Gago-Dominguez M. .
Source: Carcinogenesis, 2010 Nov; 31(11), p. 1964-71.
EPub date: 2010-08-23.
PMID: 20732908
Related Citations

Sequence variant on 3q28 and urinary bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study.
Authors: Stern M.C. , Van Den Berg D. , Yuan J.M. , Conti D.V. , Gago-Dominguez M. , Pike M.C. , Xiang Y.B. , Gao Y.T. , Cortessis V.K. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2009 Nov; 18(11), p. 3057-61.
EPub date: 2009-10-20.
PMID: 19843673
Related Citations

Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the international consortium of bladder cancer.
Authors: Stern M.C. , Lin J. , Figueroa J.D. , Kelsey K.T. , Kiltie A.E. , Yuan J.M. , Matullo G. , Fletcher T. , Benhamou S. , Taylor J.A. , et al. .
Source: Cancer research, 2009-09-01; 69(17), p. 6857-64.
EPub date: 2009-08-25.
PMID: 19706757
Related Citations

Urinary tract infections and reduced risk of bladder cancer in Los Angeles.
Authors: Jiang X. , Castelao J.E. , Groshen S. , Cortessis V.K. , Shibata D. , Conti D.V. , Yuan J.M. , Pike M.C. , Gago-Dominguez M. .
Source: British journal of cancer, 2009-03-10; 100(5), p. 834-9.
EPub date: 2009-01-27.
PMID: 19174821
Related Citations

Water intake and bladder cancer risk in Los Angeles County.
Authors: Jiang X. , Castelao J.E. , Groshen S. , Cortessis V.K. , Shibata D.K. , Conti D.V. , Gago-Dominguez M. .
Source: International journal of cancer, 2008-10-01; 123(7), p. 1649-56.
PMID: 18623082
Related Citations

Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer.
Authors: Yuan J.M. , Chan K.K. , Coetzee G.A. , Castelao J.E. , Watson M.A. , Bell D.A. , Wang R. , Yu M.C. .
Source: Carcinogenesis, 2008 Jul; 29(7), p. 1386-93.
EPub date: 2008-06-09.
PMID: 18544563
Related Citations




Back to Top