Lung cancer is a leading cause of cancer morbidity and mortality globally and in China. Beyond established nonmodifiable and modifiable risk factors such as age and smoking, lifestyle exposures including diet and sleep have been investigated for possible roles in lung carcinogenesis. Polyunsaturated fatty acids (PUFAs) — notably omega-3 and omega-6 fatty acids — have produced inconsistent associations with lung cancer in prior studies. Similarly, adverse sleep characteristics have been implicated in cancer-related pathways but are often studied individually rather than as an overall pattern. This matched case-control study conducted in Chongqing, southwest China, aimed to examine associations of dietary PUFA intake and composite sleep patterns with lung cancer, and to explore whether the sleep–lung cancer association varied by PUFA intake.
The investigators conducted a hospital- and community-based matched case-control study between August 22, 2023, and September 30, 2024. Cases comprised newly or recently diagnosed lung cancer patients identified from a thoracic surgery department and the Chongqing Tumor Registration System. Eligible cases were adults with histopathologically confirmed lung cancer (ICD‑10 C33–C34), disease duration ≤2 years, and long-term Chongqing residence. Community controls were recruited from the same districts using the same sampling procedures and had no cancer history.
After exclusions for eligibility, missing data, and implausible energy intakes, the final matched analytic sample included 322 cases and 644 controls matched 1:2 by sex and age group (<45, 45–65, >65 years).
Dietary intake over the 12 months prior to diagnosis (cases) or questionnaire (controls) was assessed using a validated semi-quantitative food frequency questionnaire (SQFFQ) developed for Chongqing populations. The SQFFQ covered 119 food items with frequency and portion size estimates aided by standardized measures and a food atlas. Nutrient calculations used the Chinese Food Composition Tables (6th Edition). Daily intakes of omega-3, omega-6, and total PUFAs were summed across reported foods and expressed in grams per day. PUFA intake was analyzed both continuously (per 1 g/day) and by tertiles.
Five sleep characteristics were captured by questionnaire for the prior 12 months: sleep duration, chronotype, insomnia symptoms, snoring, and daytime sleepiness. Each favorable response (7–8 hours sleep, morning chronotype, rarely/never insomnia, no snoring, rarely/never daytime sleepiness) scored 1 point, producing a healthy sleep score ranging 0–5. Participants were categorized as unfavorable (0–1), medium (2–3), or favorable (4–5) sleep patterns.
Descriptive comparisons used t-tests, Mann–Whitney U tests, or chi-squared tests as appropriate. Multivariable conditional logistic regression conditioned on matched sets estimated odds ratios (ORs) and 95% confidence intervals (CIs). Three models were reported: crude; Model 1 adjusting for education, household income, family history of lung cancer, smoking status, and fish oil supplementation; and Model 2 further adjusting for diabetes, BMI, total energy intake, alcohol frequency, passive smoking, occupational exposure, and hot cooking oil exposure. Primary analyses assessed PUFA measures and sleep categories separately. Secondary exploratory analyses stratified sleep–lung cancer associations by median PUFA intake and tested multiplicative interactions via cross-product terms. Two-sided P < 0.05 indicated statistical significance.
Compared with matched controls, cases were more likely to report a family history of lung cancer, higher household income, passive smoking, occupational exposure, and current or former smoking. Cases had lower prevalence of diabetes and obesity (BMI ≥28 kg/m2) and were more likely to report unfavorable sleep patterns. Reported median or mean intakes of omega-3, omega-6, and total PUFAs were lower among cases versus controls.
When modeled continuously, higher omega-3 PUFA intake was consistently associated with lower odds of lung cancer. In the fully adjusted model (Model 2), each 1-g/day increase in omega-3 intake was associated with an OR of 0.82 (95% CI 0.70–0.96; P = 0.012). Omega-6 and total PUFA intakes were not statistically significant in continuous analyses in Model 2 (omega-6 OR 0.97, 95% CI 0.94–1.00, P = 0.090; total PUFA OR 0.99, 95% CI 0.97–1.01, P = 0.377).
In tertile-based analyses, participants in the highest versus lowest tertile had lower odds of lung cancer for all three PUFA measures in the fully adjusted model: omega-3 (OR 0.50, 95% CI 0.32–0.78; P = 0.002), omega-6 (OR 0.50, 95% CI 0.31–0.80; P = 0.004), and total PUFA (OR 0.48, 95% CI 0.30–0.79; P = 0.003). Trend tests across tertiles were significant for each PUFA measure.
Compared with participants with unfavorable sleep patterns (score 0–1), those with favorable sleep patterns (score 4–5) had lower odds of lung cancer in adjusted analyses. In the fully adjusted model, a favorable sleep pattern was associated with OR 0.59 (95% CI 0.40–0.87). Medium sleep patterns (score 2–3) showed intermediate estimates.
Exploratory stratified analyses dichotomized PUFA intake at the median to create lower- and higher-intake strata. The authors observed numerically lower stratum-specific ORs for the sleep–lung cancer association in the higher omega-3 intake stratum, suggesting a potentially stronger inverse association among those with higher omega-3 intake. However, formal multiplicative interaction tests were not statistically significant for the cross-product terms, indicating no robust evidence of interaction on the multiplicative scale in this sample.
Strengths of the study include matched case-control design, use of a regionally validated SQFFQ, a composite healthy sleep score capturing multiple sleep domains, and adjustment for multiple potential confounders including smoking and occupational exposures. Limitations include retrospective assessment of diet and sleep with potential recall bias, case-control design that precludes causal inference, retrospective registration of the study, and potential residual confounding. The authors conclude that higher dietary omega-3 PUFA intake and favorable sleep patterns were each associated with lower odds of lung cancer in this southwest China population, but that findings — especially for omega-6 and total PUFA where results varied by analysis method — require confirmation in prospective studies.