C‐reactive protein and colorectal adenomas: Self Defense Forces Health Study

Abstract

Chronic inflammation has been implicated in colorectal carcinogenesis. Several studies have investigated the relationship between C-reactive protein (CRP), a biomarker of inflammation, and colorectal cancer and adenomas, resulting in inconsistent findings. The present study examined the relationship between circulating levels of high-sensitivity CRP and colorectal adenomas. The study subjects comprised 646 cases of colorectal adenoma and 635 controls of normal total colonoscopy among men receiving a preretirement health examination at two hospitals of the Self Defense Forces. Statistical adjustment was made for cigarette smoking, alcohol use, body mass index, physical activity, and other potential confounders. The multivariate-adjusted geometric means showed no measurable differences between adenoma cases and controls, but were higher among cases with larger adenomas (trend P = 0.03). Likewise, although the prevalence odds of colorectal adenomas did not differ according to CRP levels as categorized at the 30th, 60th, and 90th percentiles in the controls, higher levels of CRP were associated with a statistically significant increase in the prevalence odds of large adenomas (³5 mm), but not of small adenomas (<5 mm). The multivariate-adjusted odds ratios of large adenomas for the lowest to highest categories of CRP were 1.00 (referent), 1.81 (95% confidence interval 1.17-2.80), 1.61 (95% confidence interval 1.03-2.52), and 2.21 (95% confidence interval 1.28-3.84), respectively (trend P = 0.01). A positive association between CRP and prevalence odds of large adenomas was not modified by either smoking or overweight. These findings suggest that inflammation is linked to the growth of colorectal adenomas. (Cancer Sci 2009; 100: 709-714) C hronic inflammation has been implicated in carcinogenesis. (1,2) Inflammatory cytokines are considered to promote carcinogenesis by inducing oxidative DNA damage, stimulating cell proliferation and angiogenesis, and inhibiting apoptosis.(1,2) Particular interest has been drawn to the role of inflammation in colorectal carcinogenesis. Chronic inflammatory bowel diseases are known to confer increased risk of colorectal cancer, (3,4) and use of aspirin or non-steroidal anti-inflammatory drugs has consistently been related to reduced risk of colorectal adenomas and cancer in observational and intervention studies.(5-8) Recently, several prospective studies have investigated the relationship between C-reactive protein (CRP), a biomarker of inflammation, and colorectal cancer risk, resulting in inconsistent findings. (9)(10)(11)(12)(13)(14)(15)(16) An increased risk of colorectal cancer associated with increased concentrations of CRP was first reported in the CLUE II study. (9) A positive association between CRP and colorectal caner risk was replicated in three subsequent studies, (10)(11)(12) but no such association was observed in four other studies. (13)(14)(15)(16) One of the latter studies even suggested a decreased risk associated with high concentrations of CRP. (13) Results are al...

C-reactive Protein and Risk of Colorectal Adenomas or Serrated Polyps: A Prospective Study

“…However, the existing literature on this topic is inconsistent. A recent Japanese study reported that CRP levels> 90 th percentile were associated with a >2-fold increase in the odds of large colorectal adenomas(9). A cross-sectional Chinese study also reported that elevated CRP levels were associated with increased risk of advanced adenomas and multiple adenomas(10).…”

“…While some studies have reported that CRP is associated with higher risk of colorectal adenomas (9, 10), others have found null (11-13), or even inverse associations(14). To our knowledge, no study has previously examined the association between inflammatory markers and serrated polyps (SPs), yet some of these lesions are now understood to be important CRC precursors as well.…”

Markers of systemic inflammation and colorectal adenoma risk: Meta-analysis of observational studies

“…Four studies were nested case-control studies, 9 had a case-control design, and one was cross-sectional. The studies were conducted in the United States[10,11,13,16,18,19,21-23], Japan[12,14,15,17], and the United Kingdom[20]. Four studies investigated advanced and 4 studies non-advanced adenoma.…”

“…Four studies investigated advanced and 4 studies non-advanced adenoma. Measurements methods varied greatly between studies, including INA (Immunonephelometric Assay)[12,14,19,20], ITA (Immunoturbidimetric Assay)[13,21,23], ELISA[10,13,17,18,23], DADE-Behring method[11], Chemiluminescent Immunometric Assay[16], Cytometric Bead Array[20], Cytokine/Chemokine Magnetic Bead Panel Assay[15,18,22]. Seven studies tested markers of inflammation in plasma, 5 in serum, and 2 in serum and plasma.…”

“…Stratified analyses for such potential confounding factors were limited[12,21] but showed significant interaction with smoking status and use of aspirin/NSAIDs, whereby associations were only observed in heavy smokers and non-regular aspirin users (Online Resource 2). A stratified analysis was also conducted according to adenoma localization.…”