Chronic Inflammation Toward Cancer Incidence: An Epidemiological Systematic Review

Background: It is well accepted that environment- and lifestyle-related factors (e.g., tobacco, diet, obesity and environmental pollutants) play a critical role in the development of nearly all cancers. Inflammation seems to be a major process that all of these risks factors have in common. Insight in the role of inflammation toward cancer development might have implications in prevention, early diagnosis and treatment of cancer (e.g., by selectively suppressing certain proinflammatory mediators). Aim: The aim of this review is to provide epidemiologic data on the correlation between chronic inflammation as measured by inflammatory blood parameters and the incidence of cancer. Methods: PubMed and Embase databases were searched until 2017 for English-written articles and screened by two independent authors. In vitro studies, animal studies or studies with chronically-ill subjects were excluded. Quality was assessed with the Newcastle-Ottawa scale. Results: The selected 22 observational studies included 14 nested case-control, 2 nested case-cohort and 6 prospective cohort studies. The articles originated from either Europe or the US. More than 70 different inflammatory markers were considered but C-reactive protein (CRP) was the most frequent one (followed by TNF-alpha and IL-6) and six studies combined markers of chronic inflammation into a score. Articles reported on the incidence of overall cancer (n=3) and eight site-specific cancers: non-Hodgkin lymphoma (NHL, n=1), breast (n=4), colorectal (n=6), endometrium (n=3), lung (n=3), pancreatic (n=2), prostate (n=3) and ovarian cancer (n=3). Evidence showed that elevated levels of circulating inflammatory markers are linked to an increased risk of overall, colon, endometrium, lung and ovarian cancer. The most robust and strong associations were found for colon cancer with five studies reporting significant results. Herein, CRP had the most consistent relation with odds/relative ratios ranging from 1.30 to 2.29. A definitive statement cannot be made for NHL, breast and prostate cancer due to a shortage of qualitative studies (short follow-up time, small case sample sizes) and/or inconclusive results. For pancreatic cancer, no significant results at all were found (even though these studies received the highest possible methodological quality score). Conclusion: Overall, chronic inflammation seems to play a pivotal role in cancer development. However, further research is necessary to resolve the inconclusive results and to clarify the mechanisms behind this association. Study quality improvements can be done by increasing the frequency of cytokine measures (instead of only one baseline measurement) and prolonging the follow-up.