Biomarker shows promise in predicting future lung cancer risk

The arthrobacter luteus/albumin ratio demonstrated a strong dose-response relationship with overall lung cancer risk and may be helpful in identifying individuals who should undergo screening, according to study results published in Chest.

To identify a lung cancer-related biomarker to help in screening risk stratification and prediction analyses, Jason Y. Y. Wong, ScD, research fellow in the Occupational and Environmental Epidemiology Branch of the NIH, and colleagues performed a nested case-control study using prediagnostic blood samples from the prospective, population-based PLCO randomized trial.

They specifically evaluated the association between arthrobacter luteus (Alu) copy number — which in prediagnostic leukocytes can reflect systemic genomic instability — and lung cancer risk.

The analysis involved 410 patients (62.2% men; 93.7% white; mean age, 64 years) with histologically confirmed incident lung cancer and 416 control individuals (61.1% men; 93% white; mean age, 63.7 years) from the PLCO trial. Researchers individually matched patients based on baseline age (± 5 years), sex, race/ethnicity, study center and blood draw date (± 3 months), extracting leukocyte DNA via a magnetic bead-based method.

Results indicated a strong dose-response relationship between Alu/albumin ratio and overall lung cancer risk, with the highest quartile linked to a significantly higher risk for lung cancer compared with the lowest quartile (OR = 2.43; 95% CI, 1.11-5.31). With each incremental standard deviation increase in Alu/albumin ratio, the risk for lung cancer rose 1.51 times (95% CI, 1.14-2.01).

Similarly, each standard deviation increase in Alu/albumin ratio yielded a 1.87 (95% CI, 1.19-2.94) times increased risk for lung adenocarcinoma.

No association was reported for squamous cell carcinoma, which the researchers posited may be the result of the small sample size (n = 84).

The association between Alu and lung cancer remained significant when researchers restricted the data to non-Hispanic white participants, and there was no effect modification based on age, smoking or sex.

“Our findings suggest that Alu retroelements in prediagnostic leukocytes may be a potential biomarker of future lung cancer risk,” Wong and colleagues concluded. “Residual confounding by smoking was suspected but was unlikely to have explained the observed Alu-lung cancer associations.”

The researchers added that these preliminary findings have potentially important implications for etiologic and translational lung cancer research but require replication in prospective studies with sufficient cases in special subgroups (eg, never smokers and racial/ethnic minorities) to resolve the nuances of Alu-lung cancer interrelationships.

“If our findings are confirmed, Alu retroelements potentially could be applied to identify high-risk populations that may qualify and benefit from lung cancer screening,” they wrote.