title: Chronic inflammation and risk of colorectal and other obesity-related cancers: The health, aging and body composition study.
abstract: Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults.
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.|School of Public Health, University of California, Berkeley, CA.
authors.forename: Monika
authors.initials: M
authors.lastname: Izano
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA.
authors.forename: Esther K
authors.initials: EK
authors.lastname: Wei
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Tai
authors.affiliation: Department of Community Medicine & Health Care, University of Connecticut Health Center, Farmington, CT.
authors.forename: Helen
authors.initials: H
authors.lastname: Swede
authors.affiliation: Division of General Internal Medicine, University of California, San Francisco, CA.
authors.forename: Steven
authors.initials: S
authors.lastname: Gregorich
authors.affiliation: National Institutes of Health, National Institute on Aging, National Institutes of Health, Bethesda, MD.
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Heidi
authors.initials: H
authors.lastname: Klepin
authors.affiliation: Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Satterfield
authors.affiliation: National Institutes of Health, National Institute on Aging, National Institutes of Health, Bethesda, MD.
authors.forename: Rachel
authors.initials: R
authors.lastname: Murphy
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PN.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rubin
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.|Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA.
authors.forename: Dejana
authors.initials: D
authors.lastname: Braithwaite
mesh_terms: D000368:Aged; D000375:Aging; D001823:Body Composition; D002097:C-Reactive Protein / Q000032:analysis; D002908:Chronic Disease; D015179:Colorectal Neoplasms / Q000209:etiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009765:Obesity / Q000150:complications*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: cohort study; colorectal cancer; incidence; inflammatory markers