Aflatoxin exposure is associated with an increased risk of gallbladder cancer

Abstract

Gall bladder cancer (GBC) is common among the socioeconomically deprived populations of certain geographical regions. Aflatoxin is a genotoxic hepatocarcinogen, which is recognized to have a role in the pathogenesis of hepatocellular carcinoma. However, the role of aflatoxin in the pathogenesis of GBC is largely unknown. We determined serum AFB1-Lys albumin adduct (AAA) levels as a marker of aflatoxin exposure in the patients with GBC and compared to those without GBC. The relationship of AAA levels to cytogenetic (TP53mutation&HER2/neu amplification) and radiological characteristics of the tumor was assessed. We included GBC cases (n = 51) and non-GBC controls (n = 100). Mean serum AAA levels were higher in the GBC group (n = 51) than those without GBC (n = 100) (26.1 ± 12.2 vs. 13.1 ± 11.9 ng/mL; p < .001). HER2/neu expression was associated with higher AAA levels compared to those with equivocal or negative expression (43.9 ± 3 vs. 28.6 ± 10 vs. 19.3 ± 7 ng/mL; p < .001). Older age (age >50 years) (odds ratio [OR] = 3.2 [CI: 1.3–8.2]; p = .013), positive Helicobacter pylori serology (OR = 5.1 [CI: 1.4–17.8]; p = .012), presence of GS (OR = 5 [CI: 1.5–16.9]; p = .009) and detectable AAA levels (OR = 6.8 [CI: 1.3–35.7]; p = .024) were independent risk factors for the presence of the GBC among all study subjects. Among patients harboring GS, older age (age >50 years) (OR = 4.5 [CI: 1.3–14.9]; p = .015), female gender (OR = 3.8 [CI: 1.2–12.5]; p = .027), presence of multiple GS (OR = 21.9 [CI: 4.8–100.4]; p < .001) and high serum AAA levels (OR = 5.3 [CI: 1.6–17.3]; p = .006) were independent risk factors for the presence of the GBC. Elderly age >50 years (OR = 2.6 [CI: 1.3–5.2]; p = .010) and frequent peanut consumption (OR = 2.3 [CI: 1.1–4.9]; p = .030) were independent risk factors for high serum AAA levels. The current study has implications for the prevention of GBC through the reduction of dietary aflatoxin exposure.