TY - JOUR
T1 - Interleukin-6 and risk of colorectal cancer
T2 - results from the CLUE II cohort and a meta-analysis of prospective studies
AU - Kakourou, Artemisia
AU - Koutsioumpa, Charalampia
AU - Lopez, David S.
AU - Hoffman-Bolton, Judith
AU - Bradwin, Gary
AU - Rifai, Nader
AU - Helzlsouer, Kathy J.
AU - Platz, Elizabeth A.
AU - Tsilidis, Konstantinos K.
N1 - Funding Information:
The authors thank Despoina Capothanassi for her statistical programming support, Dr. Thomas P Erlinger for his support of research on inflammation biomarkers and colorectal cancer risk in CLUE, and the authors of the original studies (Drs. Katriina Heikkila, Andrew Chan, Gloria Ho, and Mingyang Song), who kindly and promptly replied to our requests for additional information. Cancer incidence data were provided by the Maryland Cancer Registry, Center for Cancer Prevention and Control, Department of Health and Mental Hygiene, 201 W. Preston Street, Room 400, Baltimore, MD 21201, http://phpa.dhmh.maryland.gov/cancer , 410-767-4055. We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, the Washington County Cancer Registry, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention (CDC) for the funds that helped support the availability of the cancer registry data. The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the Department of Health and Mental Hygiene.
Funding Information:
This research was funded by the American Institute for Cancer Research and the Maryland Cigarette Restitution Fund at Johns Hopkins, and the National Cancer Institute (P30 CA006973 to W.G. Nelson).
Publisher Copyright:
© 2015, Springer International Publishing Switzerland.
PY - 2015/10/14
Y1 - 2015/10/14
N2 - Purpose: The association between prediagnostic interleukin-6 (IL-6) concentrations and risk of colorectal cancer was evaluated in a nested case–control study and a meta-analysis of prospective studies. Methods: Colorectal cancer cases (n = 173) and matched controls (n = 345) were identified between 1989 and 2000 among participants in the CLUE II cohort of Washington Country, Maryland. Matched odds ratios and the corresponding 95 % confidence intervals (CIs) were estimated using conditional logistic regression models. Results: Participants in the highest third of plasma IL-6 concentration had a 2.48 times higher risk of colon cancer compared to participants in the bottom third (95 % CI 1.26–4.87; p-trend 0.02) after multivariate adjustment. This association did not differ according to the stage of disease, age, sex, or other potential modifying variables and remained statistically significant after adjustment for C-reactive protein concentrations. No statistically significant association was observed for rectal cancer risk. The meta-analysis of six prospective studies yielded an increased but borderline statistically significant risk of colon cancer per 1 U increase in naturally logarithm-transformed IL-6 (summary RR 1.22; 95 % CI 1.00–1.49; I2 46 %). An inverse association was noted for rectal cancer (RR 0.69; 95 % CI 0.54–0.88; I2 0 %), but there was evidence for small-study effects (p 0.02). Conclusion: Our findings provide support for a modest positive association between IL-6 concentrations and colon cancer risk. More work is needed to determine whether IL-6 is a valid marker of colorectal inflammation and whether such inflammation contributes to colon and rectal cancer risk.
AB - Purpose: The association between prediagnostic interleukin-6 (IL-6) concentrations and risk of colorectal cancer was evaluated in a nested case–control study and a meta-analysis of prospective studies. Methods: Colorectal cancer cases (n = 173) and matched controls (n = 345) were identified between 1989 and 2000 among participants in the CLUE II cohort of Washington Country, Maryland. Matched odds ratios and the corresponding 95 % confidence intervals (CIs) were estimated using conditional logistic regression models. Results: Participants in the highest third of plasma IL-6 concentration had a 2.48 times higher risk of colon cancer compared to participants in the bottom third (95 % CI 1.26–4.87; p-trend 0.02) after multivariate adjustment. This association did not differ according to the stage of disease, age, sex, or other potential modifying variables and remained statistically significant after adjustment for C-reactive protein concentrations. No statistically significant association was observed for rectal cancer risk. The meta-analysis of six prospective studies yielded an increased but borderline statistically significant risk of colon cancer per 1 U increase in naturally logarithm-transformed IL-6 (summary RR 1.22; 95 % CI 1.00–1.49; I2 46 %). An inverse association was noted for rectal cancer (RR 0.69; 95 % CI 0.54–0.88; I2 0 %), but there was evidence for small-study effects (p 0.02). Conclusion: Our findings provide support for a modest positive association between IL-6 concentrations and colon cancer risk. More work is needed to determine whether IL-6 is a valid marker of colorectal inflammation and whether such inflammation contributes to colon and rectal cancer risk.
KW - Cohort study
KW - Colorectal cancer
KW - Inflammation
KW - Meta-analysis
UR - http://www.scopus.com/inward/record.url?scp=84941425687&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84941425687&partnerID=8YFLogxK
U2 - 10.1007/s10552-015-0641-1
DO - 10.1007/s10552-015-0641-1
M3 - Article
C2 - 26220152
AN - SCOPUS:84941425687
SN - 0957-5243
VL - 26
SP - 1449
EP - 1460
JO - Cancer Causes and Control
JF - Cancer Causes and Control
IS - 10
ER -