Cancer of the urinary bladder affects 4 to 5 times more men than women worldwide. Cigarette smoking, occupational exposures and infection with Schistosoma haematobium are well-established risk factors for this malignancy. Furthermore, several genetic polymorphisms have been associated with increased bladder cancer risk. Important gaps in knowledge remain about synergistic effects between environmental factors, gene-environment interactions, and gender differences in bladder cancer risk factors. Egypt represents a unique setting for such research, as bladder cancer continues to be the most common malignancy in men in Egypt despite recent reductions in schistosomiasis, and the ratio of men to women remains consistently high;few women in Egypt smoke cigarettes (<5%) compared to 50-70% of men;and in addition to the transitional cell type carcinoma that is predominantly observed world wide, squamous type carcinoma is very common in Egypt. We therefore propose to conduct a case-control study of bladder cancer in Egypt, with a sample size of 3,312 cases and 4 population-based controls per case.
The Specific Aims of the study are as follows: 1) to evaluate environmental risk factors for bladder cancer, in men and women combined, including infections, and interactions among these factors;2) to determine if associations between risk factors and bladder cancer are affected by gender;3) to evaluate associations between bladder cancer risk (in men and women combined) and functional polymorphism in genes that mediate the oxidative stress response;4) to evaluate interactions between environmental exposures and the candidate susceptibility genes, and to determine if gene-environment interactions exert differential effects on bladder cancer risk in men and women. Within these aims we will account for risk differences by histological type of bladder cancer (transitional vs. squamous). The results of this study will help establish the best preventive measures for bladder cancer in men and women, by appropriately directing the resources of the public health sector for effective cancer control.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA115618-05
Application #
7777429
Study Section
Special Emphasis Panel (ZRG1-HOP-N (03))
Program Officer
Su, Joseph
Project Start
2006-04-11
Project End
2012-02-28
Budget Start
2010-03-01
Budget End
2012-02-28
Support Year
5
Fiscal Year
2010
Total Cost
$442,548
Indirect Cost
Name
Georgetown University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Wang, Hongkun; Wang, Ying; Kota, Krishna K et al. (2017) Strong associations between chromosomal aberrations in blood lymphocytes and the risk of urothelial and squamous cell carcinoma of the bladder. Sci Rep 7:13493
Amr, Sania; Dawson, Rebecca; Saleh, Doa'a A et al. (2015) Pesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers. Arch Environ Occup Health 70:19-26
Wang, Hongkun; Wang, Ying; Kota, Krishna K et al. (2015) Strong association between long and heterogeneous telomere length in blood lymphocytes and bladder cancer risk in Egyptian. Carcinogenesis 36:1284-90
Goerlitz, David; Amr, Sania; Dash, Chiranjeev et al. (2014) Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt. Urol Oncol 32:47.e15-20
Amr, Sania; Dawson, Rebecca; Saleh, Doa'a A et al. (2014) Agricultural workers and urinary bladder cancer risk in Egypt. Arch Environ Occup Health 69:3-10
Zheng, Yun-Ling; Amr, Sania; Saleh, Doa'a A et al. (2012) Urinary bladder cancer risk factors in Egypt: a multicenter case-control study. Cancer Epidemiol Biomarkers Prev 21:537-46
Wolpert, Beverly J; Amr, Sania; Saleh, Doa'a A et al. (2012) Associations differ by sex for catechol-O-methyltransferase genotypes and bladder cancer risk in South Egypt. Urol Oncol 30:841-7
Goerlitz, David; El Daly, Mai; Abdel-Hamid, Mohamed et al. (2011) GSTM1, GSTT1 null variants, and GPX1 single nucleotide polymorphism are not associated with bladder cancer risk in Egypt. Cancer Epidemiol Biomarkers Prev 20:1552-4
Wolpert, Beverly J; Amr, Sania; Ezzat, Sameera et al. (2010) Estrogen exposure and bladder cancer risk in Egyptian women. Maturitas 67:353-7