ZIA CP010218-10789 (ZIA) | |||
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Title | Longitudinal Analysis of Aflatoxin and Gallbladder Cancer | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Koshiol, Jill | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $79,424 | Project Dates | 00/00/0000 - 00/00/0000 |
Fiscal Year | 2017 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) |
Gallbladder (100.0%) | ||
Research Type | |||
Exogenous Factors in the Origin and Cause of Cancer Endogenous Factors in the Origin and Cause of Cancer |
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Abstract | |||
"In 2012, gallbladder cancer (GBC) accounted for an estimated 178,000 new cancer patients and over 142,000 deaths globally. Geographically, GBC rates are strikingly variable, with the highest rates in south-central Chile and northern India. Although GBC is the most common biliary tract cancer, knowledge of GBC etiology remains limited. Gallstones are a major risk factor for GBC, but little is known about other risk factors that contribute to the development of GBC among gallstone patients. Our objective is to measure AFB1-adduct levels in pre-diagnostic blood samples from GBC cases and non-cases in order to test the hypothesis that aflatoxin exposure is associated with GBC. Aflatoxin has been hypothesized to increase risk of GBC. Exposure to aflatoxin is associated with increased risk of liver cancer and has been shown to increase cellular proliferation in the biliary tract of monkeys and humans. The excretion of aflatoxin into bile can lead to high concentrations in the biliary tree, and aflatoxin exposure has been associated with gallbladder carcinogenesis in primates. We recently demonstrated a strong association between circulating aflatoxin B1 (AFB1)-lysine adducts and GBC in humans with odds ratios (OR) of 13.2 (95% confidence interval [CI]: 4.3-47.9) for GBC versus population-based controls and 9.4 (95% CI: 2.8 to 37.2). We then verified and extended this novel association using samples from the Shanghai Biliary Tract Cancer Study focusing on the comparison between GBC and gallstones to demonstrate the association of aflatoxin with GBC independent of gallstones. Among 250 GBC patients and 250 controls with gallstones, AFB1-lysine adduct detection was nearly 3-fold higher in GBC patients (OR, 2.91; 95% CI, 1.87-4.54). Given that we see a consistent association between aflatoxin exposure and GBC in two independent populations, we propose to evaluate the association prospectively using pre-diagnostic blood samples from two existing cohorts. " |