C-Reactive Protein And Risk Of Lung Cancer: A Pooled Analysis Of 20 Prospective Cohorts

David MULLER, Imperial College London, United Kingdom
HODGE A. 2 , SEVERI G. 3 , CAI Q. 4 , MEYER K. 5 , GRANKVIST K. 6 , LANGHAMMER A. 7 , BRENNAN P. 8 , JOHANSSON M. 8

1 School of Public Health, Imperial College London, United Kingdom
2 Cancer Council Victoria, Melbourne, Australia
3 Human Genetics Foundation, Turin, Italy
4 Vanderbilt University Medical Center, Nashville, TN, United States
5 Bevital, Bergen, Norway
6 Umea University, Umea, Sweden
7 Norwegian University of Science and Technology, Trondheim, Norway
8 Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France

Background: Inflammation may have an important role in the etiology of lung cancer, and several studies have reported that C-reactive protein (CRP) is associated with risk of lung cancer. To clarify this association, we conducted a pooled analysis of CRP and lung cancer risk using data from 20 prospective cohort studies.

Methods: Within the NCI Cohort Consortium, we designed a prospective nested case-control study. Controls were selected from appropriate risk sets and were matched to cases on smoking status, sex, and age at blood draw. This analysis included 5,299 case-control pairs nested within 20 cohorts. Rate ratios (RR) and their 95% confidence intervals associated with a doubling in concentration of CRP were estimated using conditional logistic regression models.

Results: Overall, higher circulating CRP was associated with an increased risk of lung cancer (RR 1.05, 95% CI [1.03, 1.08]). This association varied strongly by smoking status (p-heterogeneity < 0.01), being similar for current (1.09 [1.05, 1.13]) and former smokers (1.09 [1.04, 1.14]), but not for never smokers (0.95 [0.91, 1.00]). The association was strongest for cancers diagnosed less than 2 years after blood draw (1.21 [1.13, 1.29], p-heterogeneity < 0.01), and weakened as time between blood draw and diagnosis increased. The association was similar across all histological subtypes, with the exception of adenocarcinoma for which we observed no association.

Conclusions: CRP is associated with risk of lung cancer. The fact that the association is restricted to ever-smokers, and is most prominent for cancers diagnosed in the first 2 years of follow-up, strongly suggests that CRP is not a causal risk factor, but rather a distal marker of disease.