Serum inflammatory markers and colorectal cancer risk and survival Sundeep Ghuman 1 , Mieke Van Hemelrijck 1 , Hans Garmo 1,2 , Lars Holmberg 1,2,3 , Håkan Malmstro ¨m 4 , Mats Lambe 2,5 , Niklas Hammar 6,7 , Go ¨ ran Walldius 7 , Ingmar Jungner 8 and Wahyu Wulaningsih * ,1,9 1 Cancer Epidemiology Group, Division of Cancer Studies, King’s College London, London, UK; 2 Regional Cancer Centre, Uppsala, Sweden; 3 Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden; 4 Department of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 5 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 6 AstraZeneca R&D, Mo ¨ lndal, Sweden; 7 Department of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 8 Department of Medicine, Clinical Epidemiological Unit, Karolinska Institutet and CALAB Research, Stockholm, Sweden and 9 Medical Research Council Unit for Lifelong Health and Ageing at University College London, London, UK Background: Inflammation has been linked with development of some cancers. We investigated systemic inflammation in relation to colorectal cancer incidence and subsequent survival using common serum inflammatory markers Design: A cohort of men and women aged 20 years and older in greater Stockholm area with serum C-reactive protein (CRP) and albumin measured between 1986 and 1999 were included (n ¼ 325 599). A subset of these had baseline measurements of haptoglobin and leukocytes. Multivariable Cox regression was performed to assess risk of colorectal cancer by levels of inflammatory markers, adjusting for potential confounders. Analyses were stratified by circulating glucose, total cholesterol and triglycerides. Overall and CRC-specific death following diagnosis were assessed as secondary outcomes. Results: A total of 4764 individuals were diagnosed with colorectal cancer. A positive association between haptoglobin and colorectal cancer incidence was found (hazard ratio (HR): 1.17; 95% CI: 1.06–1.28). A positive association was also observed with leukocytes (HR: 1.21; 95% CI: 1.03–1.42). No evidence of association was noted between CRP and colorectal cancer risk. Higher risks of all-cause death were seen with haptoglobin and leukocytes levels. Higher haptoglobin levels were linked with an increased risk of colorectal cancer death (HR: 1.19; 95% CI: 1.01–1.41). Conclusions: Prediagnostic systemic inflammation may impact colorectal cancer incidence and survival; therefore, prompting investigations linking inflammatory pathways preceding colorectal cancer with disease severity and progression. Evidence suggesting a role for inflammation in colorectal carcinogenesis is growing (Hanahan and Weinberg, 2011). For instance, inflammatory bowel disease, reflecting local inflammation of the colon, has been associated with an increased risk of colorectal cancer (Jess et al, 2012). The role of systemic inflammation in colon carcinogenesis, however, remains unclear. Chronic inflammation may initiate and promote cancer through the generation of proinflammatory cytokines and reactive oxygen species, such as interleukin-6 (IL-6), which activates transcription factors that can promote the growth of a tumour (Meira et al, 2008). Increases in white blood cells can also lead to a ‘respiratory burst’ due to an increased uptake of oxygen, resulting in more reactive oxygen species at the site of damage and DNA damage consequently (Reuter et al, 2010). In the context of colorectal cancer, over 19 observational studies have investigated a link with prediagnostic levels of inflammatory markers over the past decade (Supplementary Table S1). Most of these studies have used C-reactive protein (CRP). Findings varied, *Correspondence: Dr W Wulaningsih; E-mail: wahyu.wulaningsih@kcl.ac.uk Received 18 November 2016; revised 31 January 2017; accepted 17 March 2017; published online 4 April 2017 r 2017 Cancer Research UK. All rights reserved 0007 – 0920/17 FULL PAPER Keywords: colorectal cancer; CRP; haptoglobin; leukocytes; albumin British Journal of Cancer (2017) 116, 1358–1365 | doi: 10.1038/bjc.2017.96 1358 www.bjcancer.com | DOI:10.1038/bjc.2017.96