Higher circulating hsCRP concentration tied to risk of lung cancer
Overall, the risk of lung cancer is higher in former and current smokers with higher concentrations of high sensitivity C-reactive protein (hsCRP), according to a study. Additionally, circulating hsCRP is not associated with the risk of lung adenocarcinoma and may reflect a prediagnostic disease state rather than a causal risk for lung cancer.
“We observed a stronger association between higher hsCRP concentration and the risk of lung cancer in the first 2 years of follow-up,” researchers said.
A positive correlation existed between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio [OR] associated with a doubling in hsCRP concentration, 1.09; 95 percent CI, 1.05–1.13) and former smokers (OR, 1.09; 1.04–1.14) but not for never smokers (p<0.01 for interaction). [BMJ 2019;364:k4981]
Such correlation persisted and was robust across all histological subtypes, except for adenocarcinoma, which did not strongly correlate with hsCRP concentration irrespective of smoking status (OR for adenocarcinoma overall, 0.97; 0.94–1.01).
The strongest association between circulating hsCRP concentration and lung cancer risk occurred during the first 2 years of follow-up for former and current smokers.
“Unresolved chronic inflammation can generate reactive oxygen species and reactive nitrogen species that promote tumour growth through angiogenesis and cell proliferation,” researchers said.
“Given our finding of a weak and inconsistent association between hsCRP concentration and the risk of lung cancer in the longer term (>2 years after blood draw), systemic inflammation does not seem to be a likely driver of early stage lung cancer, or hsCRP concentration might not be capturing the risk, or both,” they added.
As such, the aetiological role of inflammation in the development of lung carcinogenesis remains in doubt, according to researchers. [Nat Rev Clin Oncol 2015;12:584-596; Mutat Res 2008;659:15-30]
Furthermore, the inclusion of hsCRP concentration in a risk model, in addition to smoking-based variables, failed to enhance risk discrimination but slightly boosted discrimination for cancers diagnosed in the first 2 years of follow-up.
“Our risk discrimination analysis—in which we found no improvement in discrimination overall and a small improvement for diagnoses in the first two years of follow-up—suggests that hsCRP concentration alone is unlikely to improve selection of patients for lung cancer screening,” researchers said.
“Further, given the lack of association between hsCRP concentration and the risk of lung adenocarcinoma, it would not be appropriate to use clinical CRP tests to rule out the presence of lung cancer during diagnostic work-up of patients who are symptomatic,” they noted.
The present case-control study included 5,299 patients with incident lung cancer, with individually incidence density-matched controls. A total of 20 prospective cohorts from Asia, Europe, Australia and US participated in the Lung Cancer Cohort Consortium. Researchers followed participants in each cohort for incident cancer diagnoses and vital status, predominantly by linkage to population registers.