A case-control study finds a strong association between coffee drinking and pancreatic cancer. On stratification, it emerges that smokers drink far more coffee than non-smokers, and smoking itself is independently associated with pancreatic cancer while lying outside the causal pathway between coffee and cancer. Coffee drinking is thus:

• A An intermediate variable in the causal chain
• B An effect modifier requiring subgroup-specific reporting
• C A confounding variable masking the true association ✓
• D Subject to differential misclassification of exposure

Explanation

A confounder must be associated with the exposure, independently associated with the outcome, and must not lie on the causal pathway between them. Smoking fulfils all three criteria here, so the apparent coffee-pancreatic cancer association is spurious and would diminish after adjustment for smoking. An intermediate variable lies inside the causal chain and should never be adjusted away, and effect modification means the true association differs across strata, neither of which applies to smoking in this scenario.

Reference: Gordis Epidemiology, 6th ed.

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Written and medically reviewed by the StethoPrep medical team.