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 - 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
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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 -