C-reactive protein and risk of lung cancer.
OBJECTIVE
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.


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%).


CONCLUSIONS
Elevated CRP levels are associated with subsequently increased lung cancer risk, suggesting an etiologic role for chronic pulmonary inflammation in lung carcinogenesis.
Chaturvedi
Anil K
AK
Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd., Rockville, MD 20852, USA. chaturva@mail.nih.gov
Caporaso
Neil E
NE
Katki
Hormuzd A
HA
Wong
Hui-Lee
HL
Chatterjee
Nilanjan
N
Pine
Sharon R
SR
Chanock
Stephen J
SJ
Goedert
James J
JJ
Engels
Eric A
EA
D017677:Age Distribution; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000453:epidemiology* / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D016014:Linear Models; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood* / Q000453:epidemiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution; D012907:Smoking / Q000453:epidemiology; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D002097:C-Reactive Protein