Genetic Susceptibility to Bladder Cancer

PRIMARY OBJECTIVES:

I. To accrue 6500 patients with superficial bladder cancer (BC) and 3500 patients with invasive BC of any age or ethnicity and of either gender.

II. To select 4500 controls, individuals will be identified from ongoing lung cancer studies from the rosters of the largest multispecialty healthcare group practice in the Houston metropolitan area, and from other sources such as assisted living facilities, independent living apartment complexes and religious congregations.

III. To assess mutagen sensitivity as measured by quantifying the number of lymphocytic chromatid breaks and comet tail moments induced by in vitro exposure to bleomycin (a radiomimetic agent) and benzo[a]pyrene diol epoxide (BPDE, a tobacco carcinogen) in 10000 BC cases and to compare these data with those already available for the 4500 controls. (Cytogenetic Component)

IV. To evaluate primary aberrations of chromosome 9 in cultured peripheral blood lymphocytes (PBLs) from a subset of 300 BC cases (150 superficial BC cases and 150 invasive BC cases) and 300 controls matched by sex, age (+/- 5 years), ethnicity, and smoking status, using chromosome-painting techniques. (Cytogenetic Component)

V. To determine genotype frequencies of a panel of genetic polymorphisms of metabolic enzyme genes, deoxyribonucleic acid (DNA) repair genes, cell cycle control genes, methylation-related genes, and disease progression related genes in 10000 BC cases and 4500 controls. (Molecular Component)

VI. To determine the relationship between chromosome 9 microsatellite instability to tumor tissue and primary chromosome 9 aberrations in lymphocytes of a subset of 300 patients. (Molecular Component).

VII. To determine the telomere length and mtDNA in peripheral blood lymphocytes (PBLs) at baseline and after g-radiation treatment in both patients and controls.

VIII. To determine the levels of telomerase activity in lymphocytes at baseline and after g-radiation treatment in both patients and controls.

IX. To measure the g-radiation-induced G2 delay in lymphocytes in both patients and controls.

X. To measure the p53 protein levels in lymphocytes at baseline and after g-radiation treatment in both patients and controls.

XI. To measure mRNA level in methylation-related genes, i.e. MBD2 (Methyl-binding domain 2), DNMT3b (DNA methyl-transferase 3b), HDAC2 (histone deacetylase 2) in lymphocytes.

XII. To measure plasma levels of growth factors such as IGF-1 (Insulin growth factor-1) and IGFBP-3 (Insulin growth factor binding protein-3) and angiogenic factors such as angiogenin.

XIII. To measure and profile serum/plasma/urine/lymphocytes biomarkers including global micro ribonucleic acid (miRNA) expression, metabolites, methylation profiles, circulating DNA and its alterations, T cell cytotoxicity and other immune related markers, gene expression, microbiome, cytokines, other proteins, and etc.

XIV. To establish lymphoblastoid cell lines from 500 BC cases and 500 controls.

XV. To perform proteomics.

XVI. Follow-up will be conducted on 6500 cases with superficial bladder cancer. (Follow-up Component)

XVII. To collect chart review data for all bladder cancer patients. (Follow-up Component)

OUTLINE:

Patients complete interview over 45 minutes for the Epidemiology Questionnaire and 45 minutes for the Nutrition Questionnaire and undergo collection of blood and urine samples at baseline. Patients may complete a follow-up interview over 30 minutes regarding cancer status, occurrence of any new diseases, nutrition, smoking and alcohol use since diagnosis. Patients' medical records are also reviewed.