Role of Aflatoxins in Cancer of Gallbladder in North India

Dear Sir,

I read with interest the hypothesis by Boby and Mathew about the possibility of microplastics being involved in the gallbladder cancer (CAGB) hotspot along the Gangetic basin.[1] Microplastics are ubiquitous, not limited to the Ganges, and as the authors admit, there is little or no evidence to link them with cancer of any system. As an oncologist who worked in North India, I found that very few patients drink water directly from the Ganges; their water supply, depending on the area of residence, is either piped supply or wells. It is also pertinent to note that this CAGB hotspot includes regions where the Ganges does not flow, ranging from northeast India, Pakistan,[2] and Nepal.[3]

The strongest link to CAGB is cholesterol gallstones (overlooked by the authors) and there is a definite dichotomy here, with North Indians (especially women) being more prone to cholesterol gallstones and South Indians to pigmentary stones; this could be due to genetic (such as ATP binding cassette transporter B1 [ABCB4] mutations mentioned by the authors) or dietary factors. Excess cholesterol in the human body is treated as a toxin and pumped out into bile by the ATP-binding cassette transporter system, the same system is used for other xenobiotics.[4] In 2008, I had hypothesized that a hepatocarcinogen like aflatoxin B (common across India due to poor food storage practices) could be pumped out along with cholesterol in individuals prone to cholesterol gallstones and thus explain the association between cholesterol gallstones and CAGB.[5] Aflatoxin contamination is common in food items such as rice, wheat, peanuts, maize, and even red chili peppers in India, where storage in hot humid conditions is conducive to the growth of the fungus, Aspergillus spp.[6]

Since then, there have been epidemiological studies from hotspots such as Chile[7], China,[8] and India[9] confirming this association. The trend in incidence of this cancer in future will provide a clue, as a fall would indicate the role of a preventable food contaminant (as food hygiene practices have been improving over the last few decades), and a rise, possibly microplastics. CAGB is a serious concern across North India as it disproportionately affects women of reproductive age and shatters family dynamics, and more research is urgently required to pinpoint the cause.

 

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Conflict of Interest

None declared.

• References

• 1 Boby JM, Mathew A. Could microplastics be the reason for the high gallbladder cancer incidence in northern India?. Indian J Med Paediatr Oncol 2025;
• 2 Bhurgri Y, Bhugri A, Hassan SH. Cancer incidents in Karachi Pakistan: first results from Karachi cancer registry. Int J Cancer 2000; 85 (03) 325-329
• 3 Thakur C, Mahato RK, Marasini S, Timalsena D, Sharma KS, Karmacharya BM. Risk factors of gallbladder cancer in Nepal: a case control study. PLoS One 2025; 20 (01) e0317249
• 4 Khunweeraphong N, Mitchell-White J, Szöllősi D. et al. Picky ABCG5/G8 and promiscuous ABCG2 - a tale of fatty diets and drug toxicity. FEBS Lett 2020; 594 (23) 4035-4058
• 5 Venniyoor A. Cholesterol gallstones and cancer of gallbladder (CAGB): molecular links. Med Hypotheses 2008; 70 (03) 646-653
• 6 Wenndt A, Sudini HK, Pingali P, Nelson R. Exploring aflatoxin contamination and household-level exposure risk in diverse Indian food systems. PLoS One 2020; 15 (10) e0240565
• 7 Nogueira L, Foerster C, Groopman J. et al.; Gallbladder Cancer Chile Working Group. Association of aflatoxin with gallbladder cancer in Chile. JAMA 2015; 313 (20) 2075-2077
• 8 Koshiol J, Zhu B, Wang R. et al. Association of aflatoxin with gallbladder cancer in a case-control study nested within a Chinese cohort. Int J Cancer 2024; 154 (05) 801-806
• 9 Yadav A, Gupta P, Gupta P. et al. Aflatoxin exposure is associated with an increased risk of gallbladder cancer. Int J Cancer 2025; 156 (02) 322-330

Publication History

Article published online:
24 July 2025