Inflammatory processes and risk of cancer: epidemiological research.

Abstract

Chronic inflammation has been implicated in cancer etiology but it is unclear whether inflammation causes cancer or results from tumor growth. To address these questions, we examined three hypotheses about the role of inflammation in incident cancers in large prospective cohorts. In the first manuscript, we hypothesized that increased levels of circulating acute-phase reactants, which are markers of inflammation, such as white blood cells, fibrinogen, factor VIII, von Willebrand factor, and C-reactive protein (CRP) (positive reactants) and decreased levels of albumin (a negative reactant) are associated with increased risk of subsequent colorectal cancer (CRC) in a prospective cohort - ARIC. After multivariate adjustment, there were statistically significant associations of CRC risk with two individual markers and a summary inflammation Z- score. For the highest versus lowest quartile, hazard ratios HR (95% confidence interval) were 1.50 (95%CI, 1.05; 2.15) for fibrinogen (p-trend across quartiles was 0.03); 1.97 (95%CI, 1.13; 3.43) for CRP (p-trend=0.02); and 1.65 (95%CI, 1.15; 2.35) for Z-score (p-trend=0.01). To our knowledge, no previous studies have examined a summary inflammation score in relation to incident cancers. The second manuscript hypothesized that the frequency of NSAIDs use was inversely associated with incident ovarian and endometrial cancers in the IWHS cohort of elderly women. We found that compared to women who reported no use of aspirin, the multivariate-adjusted HRs of ovarian cancer for those who used aspirin less than 2, 2-5 times, and 6 or more times per week were 0.83, 0.77 and 0.61, respectively (p-trend=0.04). We did not observe associations between non-aspirin NSAIDs use and ovarian cancer risk or between any NSAIDs use and endometrial cancer risk. The third manuscript examined whether elderly women (65+) suffering from an inflammatory autoimmune disease - psoriasis - have an increased risk of total, breast, lung, or colon cancers in the IWHS cohort linked to Medicare. We observed an association between psoriasis and colon cancer risk: multivariate-adjusted HR=1.57 (95%CI, 1.02; 2.42) for those with versus without psoriasis. This association was stronger for severe psoriasis. Findings from these studies give further support to the hypothesis that chronic inflammation may play a role in colorectal and ovarian carcinogenesis.