Epidemiologic Studies Cannot Reveal the True Shape of the Dose–Response Relationship for Radon-Induced Lung Cancer

A long-standing controversy is the correct shape of the dose-response relationship for lung cancer induction by inhaled radon (eg, residential radon) at low levels. A probabilistic approach is used in this commentary to show that cohort and case-control epidemiologic studies cannot reveal the true shape of the dose-response relationship for radon-induced lung cancer. Using the indicated approach, it is found that while the dose response for radon-induced lung cancer is expected to be threshold-increasing, the dose-response curve for the cancer incidence when cancers caused by smoking and other carcinogens are included is expected to be threshold-decreasing (ie, threshold-hormetic), as low-level radon can protect from cancer induction by other carcinogens via stimulating the body’s natural defenses against cancer. These defenses include DNA damage repair, removal of aberrant cells via apoptosis, suppression of cancer promoting inflammation, and anticancer immunity.