Introduction: Experimental and clinical studies have demonstrated that inflammation is associated with cancer risk and mortality. However, there are conflicting reports on the associations of biomarkers of inflammation with cancer. Because the biomarkers are systemic in origin, associations between individual biomarkers and cancer may not be always apparent. One inflammatory biomarker may correctly classify some cases and misclassify others and this could contribute to the conflicting results reported in previous studies. To further elucidate the relationship between inflammation and cancer, we investigated the associations of C-reactive protein (CRP) and leukocyte count with cancer risk and mortality using the individual biomarkers and an inflammatory score derived from the two biomarkers. We hypothesize that any observed association would be more apparent in analysis conducted using an inflammatory score compared with analysis using individual biomarkers.

Methods: We conducted this analysis among men enrolled in a prospective cohort study from Finland who had baseline examination and blood draw between March 1984 and December 1989. During an average follow-up period ranging from 23-28 years (till December 2012), 653 men developed cancer and 287 cancer deaths occurred. Cancer cases and deaths were ascertained through linkage to nationwide Finnish cancer Registry and Statistics Finland, respectively. Participants were categorized into quartiles based on the distribution of the biomarkers within the study population. In addition to individual biomarker analysis, the biomarkers were analyzed together using a standardized combined z-score. We computed the score for each biomarker based on the subject's biomarker concentration (x), study mean (μ) and study standard deviation (σ) and computed a z-score with z = ( x - μ )/σ . The combined z-score was the sum of the subject's individual CRP and leukocyte z-scores. We used Cox proportional hazard models to evaluate associations of the biomarkers, including the z-scores, with cancer risk and mortality, adjusting for confounders (age at baseline, examination year, smoking history (pack-years), alcohol consumption, energy intake, and cardiorespiratory fitness).

Results: In multivariable-adjusted analyses using individual biomarkers, elevated leukocyte count (HR= 1.31, 95%CI 1.04-1.66, p-trend=0.19) and CRP concentration (HR= 1.23, 95%CI 0.97-1.55, p-trend=0.18) were not associated with statistically significantly increased risk of cancer and cancer mortality (HR=1.15, 95%CI 0.81-1.64, p-trend=0.43 for CRP and HR=1.39, 95%CI 0.98-1.97, p-trend=0.42 for leukocyte count). However, in analyses conducted using the derived z-scores, men with elevated z-scores had significantly increased risk of cancer. The HRs comparing men within the highest z-score quartile to those within the lowest z-score quartile were 1.47 (95%CI 1.16-1.88, p-trend<0.01) and 1.48 (95% CI 1.03-2.14, p-trend=0.11) for cancer risk and mortality, respectively.

Conclusions: In this prospective cohort study with long follow-up, an inflammatory biomarker score was more predictive of cancer risk than individual biomarkers alone. Our results indicate that combining biomarkers of inflammation may provide better clues to elucidating the associations of inflammation with cancer risk and mortality.

Citation Format: Leavitt Morrison, Mark Ziegler, Jari Laukkanen, Sudhir Kurl, Kimmo Ronkainen, Jussi Kauhanen, Adetunji T. Toriola. Elucidating the associations of inflammation with cancer risk and mortality using an inflammatory score: Results from a prospective cohort study [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A06.