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

• Published in: International journal of cancer 2024-03, Vol.154 (5), p.801-806
• Main Authors: Koshiol, Jill, Zhu, Bin, Wang, Renwei, Hildesheim, Allan, Gao, Yu‐Tang, Egner, Patricia A., Yuan, Jian‐Min, Groopman, John D.
• Format: Article
• Language: English
• Subjects: Adducts; aflatoxin; Aflatoxin B1; Aflatoxin B1 - adverse effects; Aflatoxin B1 - analysis; Aflatoxins - analysis; Aflatoxins - toxicity; Albumin; Albumins; Cancer; Case-Control Studies; China - epidemiology; Cohort Studies; Epidemiology; Gallbladder cancer; Gallbladder Neoplasms - chemically induced; Gallbladder Neoplasms - epidemiology; gallstones; Health risk assessment; Humans; incidence; Lysine; Male; Medical research
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.34755

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 3.36 pg/mg vs undetectable, suggesting a dose‐response (Ptrend = .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. What's new? Aflatoxin B1 exposure has been associated with gallbladder cancer, but only in cross‐sectional studies. This case‐control study nested within the Shanghai Cohort Study provides first evidence that exposure precedes disease development. The risk of gallbladder cancer was twice as high among individuals with detectable vs undetectable baseline aflatoxin B1‐lysine albumin adducts. The results suggested a long‐term, persistent effect of aflatoxin B1 exposure on gallbladder cancer risk, and the association was stronger among individuals with self‐reported gallstones. Aflatoxin B1 may contribute to gallbladder cancer development, and aflatoxin abatement programs could help reduce the incidence of gallbladder cancer in high‐risk areas.