C-reactive protein and risk of lung cancer

Abstract

Purpose: Chronic inflammation could play a role in lung carcinogenesis, underscoring the potential for lung cancer prevention and screening. We investigated the association of circulating high-sensitivity C-reactive protein (CRP, an inflammation biomarker) and CRP single nucleotide polymorphisms (SNPs) with prospective lung cancer risk.

Patients and methods: We conducted a nested case-control study of 592 lung cancer patients and 670 controls with available prediagnostic serum and 378 patients and 447 controls with DNA within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 77,464). Controls were matched to patients on age, sex, entry year, follow-up time, and smoking. We measured CRP levels in baseline serum samples and genotyped five common CRP SNPs.

Results: Elevated CRP levels were associated with increased lung cancer risk (odds ratio [OR], 1.98; 95% CI, 1.35 to 2.89; P-trend < .001 for fourth quartile [Q4, > or = 5.6 mg/L] v Q1 [< 1.0 mg/L]). The CRP association did not differ significantly by histology, follow-up time, or smoking status, but was most apparent for squamous cell carcinomas (OR, 2.92; 95% CI, 1.30 to 6.54), 2 to 5 years before lung cancer diagnosis (OR, 2.33; 95% CI, 1.24 to 4.39), and among former smokers (OR, 2.48; 95% CI, 1.53 to 4.03) and current smokers (OR, 1.90; 95% CI, 1.06 to 3.41). Although CRP SNPs and haplotypes were associated with CRP levels, they were not associated with lung cancer risk. Ten-year standardized absolute risks of lung cancer were higher with elevated CRP levels among former smokers (Q4: 2.55%; 95% CI, 1.98% to 3.27% v Q1: 1.39%; 95% CI, 1.07% to 1.81%) and current smokers (Q4: 7.37%; 95% CI, 5.81% to 9.33% v Q1: 4.03%; 95% CI, 3.01% to 5.40%).

Conclusion: Elevated CRP levels are associated with subsequently increased lung cancer risk, suggesting an etiologic role for chronic pulmonary inflammation in lung carcinogenesis.

Fig 1.

Association of circulating C-reactive protein (CRP) levels with lung cancer risk across (A) lung cancer histologies (squamous cell carcinomas [SCCs; n = 126 lung cancers], adenocarcinomas [ACs; n = 269], small-cell carcinomas [n = 75], large-cell carcinomas [n = 36], and cancers of other/unknown histologies [n = 86]), (B) follow-up time (< 1 year [n = 128 lung cancers], 1 to 2 years [n = 70], 2 to 5 years [n = 238], and 5+ years [n = 156]), and (C) smoking strata (never smokers [n = 39 lung cancers], former smokers [n = 318], and current smokers [n = 236]). Odds ratios (ORs) and 95% CIs were estimated in conditional logistic regression models, and by virtue of matching, incorporated adjustment for age, sex, year of random assignment, follow-up time, and smoking (see Patients and Methods for details). ORs and 95% CIs are shown for the second (Q2), third (Q3), and fourth (Q4) quartiles compared with the first quartile (Q1). P-trend values for ORs across CRP quartiles are shown. P-heterogeneity values are shown for the association of CRP quartiles (treated as an ordinal variable with 1 df) with risk of specific lung cancer histologic subsites (A), as well as for the multiplicative statistical interaction between CRP levels and follow-up time (B) and cigarette smoking (C) on lung cancer risk.