Study
PLCO
(Learn more about this study)
Project ID
2010-0113
Initial CDAS Request Approval
Nov 22, 2010
Title
Arylamine hemoglobin (Hgb)-adducts and bladder cancer risk in never-smokers within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO)
Summary
Several members of the arylamine family of compounds have been classified as human bladder carcinogens. Exposure to arylamines can occur from a variety of sources including tobacco smoke, which is an established major source for certain arylamines including 4-aminobiphenyl (4-ABP) and 2 -naphthylamine. Oxidation of arylamines can form reactive species that can form adducts with Hgb, reflecting exposure received over the life span of red blood cells (RBCs) (120 days). Data from a case control study suggest that other adducts, including 2,6-dimethylaniline (DMA), 3,5-DMA, and 3- ethylaniline(EA) Hgb-adducts, which can be derived from sources such as drugs, pesticides, and dyes, may be associated with bladder cancer among never-smokers[1]. However, there are a limited number of cohorts that can evaluate the relationship between Hgb-adducts and bladder cancer since most do not store RBCs. The proposed study has the potential to identify new risk factors for bladder cancer among never-smokers, whose etiology is for the most part still unexplained. To address this question we propose a nested-case control study of never-smoking cases (N=100) with pathologically confirmed incident bladder cancer, diagnosed at least two years from the date of blood collection and with no previous history of cancer (except for non-melanoma skin cancers). For each case, we will select two never smoker controls matched on the basis of age (± 5 years), sex, race, and blood collection date (±1 month) from among cohort members who were cancer-free at the time of case diagnosis. The laboratory of Tobias Weiss will evaluate arylamine Hgb-adducts using packed RBCs. Odds ratios (ORs) relating categories of analyte concentration (defined using control quartiles) to bladder cancer risk will be computed by conditional logistic regression. This study will be sufficiently powered to detect mean case-control differences that range from 0.5 to 396 ng/l. depending on the adduct. To the best of our knowledge, this will be the first study to evaluate a spectrum of arylamine Hgb-adducts and risk of bladder cancer among never-smokers in any prospective cohort study.
Aims
The primary aim of this proposal is to measure a spectrum arylamine Hgb-adducts and evaluate their association with risk for bladder cancer among never-smokers. Members of the arylamine family have been classified and regulated as human bladder carcinogens and data from case-control studies suggest measurement of Hgb-adducts as a sensitive and specific marker of bladder cancer risk. We hypothesize that increased levels of the arylamine Hgb-adducts we propose to evaluate in this proposal are associated with bladder cancer risk among never-smokers.
Collaborators
Nilanjan Chatterjee (DCEG)
Dale Larson (Charles Stark Draper Laboratory)
Jonine Figueroa (DCEG)
Nathaniel Rothman (DCEG)
Debra Silverman (DCEG)
Tobais Weiss (Institut für Prävention und Arbeitsmedizin (IPA))
