TY - JOUR
T1 - A Prospective study of macrophage inhibitory cytokine-1 (MIC-1/GDF15) and risk of colorectal cancer
AU - Mehta, Raaj S.
AU - Song, Mingyang
AU - Bezawada, Navya
AU - Wu, Kana
AU - Garcia-Albeniz, Xabier
AU - Morikawa, Teppei
AU - Fuchs, Charles S.
AU - Ogino, Shuji
AU - Giovannucci, Edward L.
AU - Chan, Andrew T.
N1 - Funding Information:
This work was supported by grants from the US National Institute of Health (P01 CA55075, UM1CA167552, P50CA127003, P01CA087969, R01CA151993, R01 CA137178, and K24 DK098311). ATC is a Damon Runyon Cancer Research Foundation Clinical Investigator. XGA is the recipient of an ASISA Fellowship and Sociedad Española de Oncología Médica grant.
PY - 2014/4
Y1 - 2014/4
N2 - Background Chronic inflammation plays a role in the development of colorectal cancer (CRC). The novel plasma inflammatory biomarker macrophage inhibitory cytokine-1 (MIC-1, GDF15) may have a direct mechanistic role in colorectal carcinogenesis. Methods We conducted a prospective, nested, case-control study of incident CRC among men and women who provided a prediagnostic blood specimen. We used an enzyme-linked immunosorbent assay to measure MIC-1 and examined associations between quintiles of MIC-1 and CRC using logistic regression adjusted for matching factors (age and date of blood draw), risk factors, and other plasma inflammatory markers. We also assessed the relationship between MIC-1 levels and prostaglandin-endoperoxide synthase 2 (PTGS2)/cyclooxygenase-2 (COX-2) enzyme status in tumors with available tissue for analysis. All statistical tests were two-sided. Results Compared with men and women within the lowest quintile of plasma MIC-1, the multivariable relative risk (RR) for CRC was 1.93 (95% confidence interval [CI] = 1.27 to 2.94) for the highest quintile (Plinear trend =. 004). In an exploratory analysis, we found that among individuals with high plasma MIC-1 levels (quintiles 2-5), compared with nonuse, regular use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a lower risk of PTGS2-positive CRC (multivariable RR = 0.60; 95% confidence interval = 0.41 to 0.88) but not PTGS2-negative CRC (multivariable RR = 1.21; 95% CI = 0.71 to 2.07). In contrast, among individuals with low MIC-1 levels (quintile 1), aspirin and NSAID use was not associated with a lower risk of PTGS2-positive CRC (multivariable RR = 0.57; 95% CI = 0.21 to 1.54) or PTGS2-negative CRC (multivariable RR = 1.41; 95% CI = 0.47 to 4.23). Conclusions Our results support an association between higher levels of circulating MIC-1 (GDF15) and CRC. Aspirin/NSAID use appeared to lower risk of PTGS2-positive cancers, particularly among individuals with high levels of circulating MIC-1.
AB - Background Chronic inflammation plays a role in the development of colorectal cancer (CRC). The novel plasma inflammatory biomarker macrophage inhibitory cytokine-1 (MIC-1, GDF15) may have a direct mechanistic role in colorectal carcinogenesis. Methods We conducted a prospective, nested, case-control study of incident CRC among men and women who provided a prediagnostic blood specimen. We used an enzyme-linked immunosorbent assay to measure MIC-1 and examined associations between quintiles of MIC-1 and CRC using logistic regression adjusted for matching factors (age and date of blood draw), risk factors, and other plasma inflammatory markers. We also assessed the relationship between MIC-1 levels and prostaglandin-endoperoxide synthase 2 (PTGS2)/cyclooxygenase-2 (COX-2) enzyme status in tumors with available tissue for analysis. All statistical tests were two-sided. Results Compared with men and women within the lowest quintile of plasma MIC-1, the multivariable relative risk (RR) for CRC was 1.93 (95% confidence interval [CI] = 1.27 to 2.94) for the highest quintile (Plinear trend =. 004). In an exploratory analysis, we found that among individuals with high plasma MIC-1 levels (quintiles 2-5), compared with nonuse, regular use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a lower risk of PTGS2-positive CRC (multivariable RR = 0.60; 95% confidence interval = 0.41 to 0.88) but not PTGS2-negative CRC (multivariable RR = 1.21; 95% CI = 0.71 to 2.07). In contrast, among individuals with low MIC-1 levels (quintile 1), aspirin and NSAID use was not associated with a lower risk of PTGS2-positive CRC (multivariable RR = 0.57; 95% CI = 0.21 to 1.54) or PTGS2-negative CRC (multivariable RR = 1.41; 95% CI = 0.47 to 4.23). Conclusions Our results support an association between higher levels of circulating MIC-1 (GDF15) and CRC. Aspirin/NSAID use appeared to lower risk of PTGS2-positive cancers, particularly among individuals with high levels of circulating MIC-1.
UR - http://www.scopus.com/inward/record.url?scp=84898920630&partnerID=8YFLogxK
U2 - 10.1093/jnci/dju016
DO - 10.1093/jnci/dju016
M3 - Article
C2 - 24565956
AN - SCOPUS:84898920630
SN - 0027-8874
VL - 106
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 4
ER -