Gallbladder Cancer Risk Factors in Northeast India: A Mixed-method Integration of Population Attributable Fractions With Global Evidence.

BACKGROUND

Gallbladder cancer (GBC) exhibits profound geographical disparity, with Northeast (NE) India bearing one of the world's highest incidence rates. This study aimed to quantify the population-level burden of GBC risk factors in NE India and integrate these findings with global evidence through a mixed-method approach.

METHODS

This mixed-method study integrated primary data from 391 confirmed GBC patients in NE India with an umbrella review of 14 global meta-analyses. Regional prevalence of risk factors was calculated with 95% confidence intervals (CIs). Population Attributable Fractions (PAFs) were computed for exposures with established global relative risks (RRs). The quality of meta-analyses was assessed using A MeaSurement Tool to Assess systematic Reviews 2. Sensitivity analyses were conducted to check the robustness of the findings.

RESULTS

The analysis quantified a dominant PAF of 65.2% (95% CI: 49.9-77.0) for gallbladder disease (gallstones), solidifying its role as the principal driver of GBC. Heavy alcohol consumption (>50 g/day) contributed a significant PAF of 20.9% (9.1-34.7). Despite a known global RR, cigarette smoking had a modest PAF (5.4%), reflecting its lower regional prevalence. Crucially, the study identified a suite of highly prevalent, region-specific exposures absent from global syntheses, including smokeless tobacco (50.4%), betel nut chewing (56.8%), reliance on tubewell water (66.0%), and near-universal mustard oil use (96%), for which PAFs could not be calculated due to a lack of global risk estimates.

CONCLUSION

Although gallstones and alcohol remain major contributors, the GBC burden in NE India is shaped by several understudied regional exposures. These findings underscore the need to reinforce established prevention strategies and to generate region-specific evidence through well-designed epidemiological studies. The absence of a regional control group may limit the ability to derive true population-level estimates; therefore, the PAF results should be interpreted with caution. Future population-based case-control studies in NE India are needed to establish more accurate exposure-risk relationships.