Association of aflatoxin with gallbladder cancer in a case-control study nested within a Chinese cohort

We evaluated whether aflatoxin B₁ (AFB₁) exposure was associated with later risk of developing gallbladder cancer (GBC). We measured AFB₁-lysine albumin adducts in baseline samples from the Shanghai Cohort Study of 18 244 men aged 45 to 64 years (recruited 1986-1989). We included 84 GBC cases with sufficient serum and 168 controls matched on age at sample collection, date of blood draw and residence. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for detectable vs non-detectable AFB₁-lysine albumin adducts and gallbladder cancer. AFB₁-lysine albumin adducts were detected in 50.0% of GBC cases, and risk of GBC was twice as high in those with detectable vs undetectable levels (OR = 2.0, 95% CI = 1.0-3.9). ORs ranged from 1.8 (95% CI = 0.75-4.3) for 0.5 to <1.75 pg/mg vs undetectable adduct levels to 2.2 (95% CI = 0.91-5.6) for >3.36 pg/mg vs undetectable, suggesting a dose-response (P_trend = .05). When restricted to cases diagnosed before the median time to diagnosis after blood draw (18.4 years), results were similar (OR = 2.2, 95% CI = 0.80-5.8) to those for the entire follow-up duration. The OR was 9.4 (95% CI = 1.7-51.1) for individuals with detectable AFB₁-lysine albumin adducts and self-reported gallstones compared to individuals with neither. Participants with detectable AFB₁-lysine albumin adducts at baseline had increased risk of developing GBC, replicating the previously observed association between AFB₁ exposure and providing the first evidence of temporality.