interstitial Lung Disease significantly Increases Lung Cancer Risk Across All Histologic Subtypes

New research published in JAMA Network Open establishes a robust link between interstitial lung disease (ILD) and an elevated risk of developing lung cancer, even after accounting for genetic and familial factors.

Groundbreaking Study Establishes ILD-Lung Cancer Link

A thorough study utilizing Swedish population data has provided compelling evidence that interstitial lung disease (ILD) is a significant risk factor for lung cancer.The research, published in JAMA Network Open, is the first to employ a sibling-controlled design, effectively addressing potential genetic predispositions and familial confounding that may have obscured this association in previous investigations.

“Our findings suggest that the presence of ILD should be incorporated into lung cancer risk assessment models,” commented the study’s investigators. Prior to this analysis, while an association between ILD and lung cancer had been hypothesized, it had not been definitively established, notably after controlling for genetic factors.

Study Design and Methodology

The study drew upon data from the Swedish Total Population Register and the Swedish Multi-generation Register,identifying 5,425,976 individuals. Of these, 14,624 had a diagnosis of ILD, while the remaining 5,411,352 formed the general population control group. Participants were born between 1932 and 1987, with a follow-up period extending from January 1, 1987, to December 31, 2016.

To ensure the robustness of the findings, the researchers employed both population-based and sibling-controlled analytical designs. The association between ILD and lung cancer was evaluated using multivariable hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs).

Key Findings: A Widespread Impact

Over the 30-year follow-up period, the study observed a marked difference in lung cancer incidence between the two groups. A total of 227 lung cancer cases were diagnosed in individuals with ILD (incidence rate of 355.4 per 100,000 person-years), compared to 40,592 cases in those without ILD (incidence rate of 26.2 per 100,000 person-years).

After adjusting for crucial factors such as sex, age, calendar period, educational attainment, and smoking-related diseases, individuals with ILD demonstrated a significantly higher risk of developing lung cancer. The overall hazard ratio for lung cancer in the ILD group was 2.16 (95% CI = 1.89-2.46).This elevated risk was also confirmed in the sibling-controlled analyses,where the HR was 2.91 (95% CI = 1.98-4.27), underscoring the independent contribution of ILD.

Increased Risk Across All Lung Cancer Subtypes

Crucially, the study revealed that ILD is associated with an increased risk for virtually all examined histologic subtypes of lung cancer:

Adenocarcinoma: HR = 1.60 (95% CI = 1.28-2.01)
Squamous cell carcinoma: HR = 2.56 (95% CI = 1.99-3.29)
Small cell carcinoma: HR = 3.29 (95% CI = 2.32-4.68)
Other histologic types: HR = 2.32 (95% CI = 1.78-3.01)

The sibling-controlled analyses generally mirrored these findings,reinforcing the strength of the association across different cancer types.

The investigators concluded, “This study is the first, to our knowledge, to use a sibling-controlled design, thereby incorporating genetic considerations and minimizing potential familial confounding. Our findings indicate that ILD is associated with an elevated risk of lung cancer,even after adjusting for familial factors. Furthermore, additional analyses across different histological subtypes of lung cancer demonstrated that ILD increases the risk for all subtypes examined.”

This research highlights the critical need for clinicians to consider ILD as a significant factor in lung cancer risk assessment, possibly leading to earlier detection and improved patient outcomes.

Corresponding authors:

Weimin Ye, MD, PhD, Karolinska Institutet, Stockholm, Sweden
Mingqiang kang, MD, PhD, Fujian Medical University Union Hospital, Fuz