Risk of lung cancer among patients with idiopathic interstitial lung disease: A cohort study using All of Us research program data.

Abstract

e20089 Background: Interstitial lung disease (ILD), a collection of heterogeneous conditions characterized by lung inflammation and scarring, shares molecular mechanisms with lung cancer. Previous studies in homogeneous European or Asian cohorts demonstrated a 7-20% increased risk of lung cancer among individuals with ILD. This study assessed the association between idiopathic ILD and lung cancer using a case-control study design with cases defined as patients with lung cancer and controls as patients with colon cancer in a large, diverse U.S. population dataset. Methods: The NIH All of Us Controlled Tier Dataset, version 8, includes 393,596 participants with Electronic Health Records information, from which 2,070 individuals had a diagnosis of lung cancer (though the data did not allow for parsing by histologic types of lung cancer), and 3,565 individuals had a diagnosis of colon cancer. Among these 5,635 individuals with cancer, 178 had a documented idiopathic ILD diagnosis. Univariable followed by multivariable logistic regression models were used to evaluate the association between idiopathic ILD and lung cancer (versus colon cancer), adjusting for age, sex, race, smoking status, income, and education level. Results: Among 5,635 individuals with cancer, 68.7% were White, 14.6% Black or Black-American, 10.9% Hispanic, and 5.8% of other races. Within this group, 2,070 had lung cancer, 129 (6.2%) of whom had idiopathic ILD, compared to 49 (1.4%) of 3,565 individuals with colon cancer [OR 4.77; 95% CI: 3.41-6.66]. In the multivariable analysis, idiopathic ILD remained an independent risk factor for lung cancer [aOR 4.37; 95% CI: 2.94-6.51; p < 0.0001]. Within the logistic regression model, other risk factors included smoking [aOR 3.18; 95% CI: 2.75-3.66; p < 0.0001], female sex [aOR 1.27; 95% CI: 1.11-1.45; p = 0.0004], and lower education levels. Among ILD patients, those with and without lung cancer were similar in age, sex, race, smoking history, income, and education (all p > 0.05). Notably, 94.6% (122 out of 129) of lung cancer cases in the group with ILD occurred in patients with the pulmonary fibrosis subtype. Discussion: This study replicates the finding from prior studies that ILD is associated with an increased risk of lung cancer, but within the diverse population of the All of Us dataset, extending the generalizability of ILD as a risk factor in pulmonary carcinogenesis. Notably, even after accounting for smoking and other potential confounders, ILD remained a strong independent predictor of lung cancer, indicating that ILD may independently drive carcinogenesis. Conclusions: ILD increases lung cancer risk, with smoking as an additive factor. These findings support implementing and testing preventive strategies, including education, smoking cessation, and routine low-dose CT screening, for individuals with ILD.