TY - JOUR
T1 - Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition
AU - Jenab, Mazda
AU - Riboli, Elio
AU - Cleveland, Rebecca J.
AU - Norat, Teresa
AU - Rinaldi, Sabina
AU - Nieters, Alexandra
AU - Biessy, Carine
AU - Tjønneland, Ann
AU - Olsen, Anja
AU - Overvad, Kim
AU - Grønbæk, Henning
AU - Clavel-Chapelon, Françoise
AU - Boutron-Ruault, Marie Christine
AU - Linseisen, Jakob
AU - Boeing, Heiner
AU - Pischon, Tobias
AU - Trichopoulos, Dimitrios
AU - Oikonomou, Eleni
AU - Trichopoulou, Antonia
AU - Panico, Salvatore
AU - Vineis, Paolo
AU - Berrino, Franco
AU - Tumino, Rosario
AU - Masala, Giovanna
AU - Peters, Petra H.
AU - Van Gils, Carla H.
AU - Bueno-de-Mesquita, H. Bas
AU - Ocké, Marga C.
AU - Lund, Eiliv
AU - Mendez, Michelle A.
AU - Tormo, María José
AU - Barricarte, Aurelio
AU - Martínez-García, Carmen
AU - Dorronsoro, Miren
AU - Quirós, José Ramón
AU - Hallmans, Göran
AU - Palmqvist, Richard
AU - Berglund, Göran
AU - Manjer, Jonas
AU - Key, Timothy
AU - Allen, Naomi E.
AU - Bingham, Sheila
AU - Khaw, Kay Tee
AU - Cust, Anne
AU - Kaaks, Rudolf
PY - 2007/7/15
Y1 - 2007/7/15
N2 - Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF-I and decreasing the bioactivity of some of its binding proteins. The objective of this study was to determine the association of increasing levels of serum C-peptide, a biomarker of pancreatic insulin secretion, and IGF binding proteins (IGFBP) -1 and -2 with colorectal cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 Western European countries. A total of 1,078 colorectal cancer cases were matched (age, date of blood donation, fasting status, gender, study center) to an equal number of control subjects. Relative cancer risks were estimated using conditional logistic regression models. Serum C-peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile (OR = 1.56, 95% CI = 1.16-2.09, ptrend <0.01), which was slightly attenuated after adjustment for BMI and physical activity (OR = 1.37, 95% CI = 1.00-1.88, ptrend = 0.10). When stratified by anatomical site, the cancer risk was stronger in the colon (OR = 1.67, 95% CI = 1.14-2.46, ptrend <0.01) than in the rectum (OR = 1.42, 95% CI = 0.90-2.25, ptrend = 0.35). The cancer risk estimates were not heterogeneous by gender or fasting status. No clear colorectal cancer risk associations were observed for IGFBP-1 or -2. This large prospective study confirms that hyperinsulinemia, as determined by C-peptide levels, is associated with an increased colorectal cancer risk.
AB - Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF-I and decreasing the bioactivity of some of its binding proteins. The objective of this study was to determine the association of increasing levels of serum C-peptide, a biomarker of pancreatic insulin secretion, and IGF binding proteins (IGFBP) -1 and -2 with colorectal cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 Western European countries. A total of 1,078 colorectal cancer cases were matched (age, date of blood donation, fasting status, gender, study center) to an equal number of control subjects. Relative cancer risks were estimated using conditional logistic regression models. Serum C-peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile (OR = 1.56, 95% CI = 1.16-2.09, ptrend <0.01), which was slightly attenuated after adjustment for BMI and physical activity (OR = 1.37, 95% CI = 1.00-1.88, ptrend = 0.10). When stratified by anatomical site, the cancer risk was stronger in the colon (OR = 1.67, 95% CI = 1.14-2.46, ptrend <0.01) than in the rectum (OR = 1.42, 95% CI = 0.90-2.25, ptrend = 0.35). The cancer risk estimates were not heterogeneous by gender or fasting status. No clear colorectal cancer risk associations were observed for IGFBP-1 or -2. This large prospective study confirms that hyperinsulinemia, as determined by C-peptide levels, is associated with an increased colorectal cancer risk.
KW - C-peptide
KW - Colorectal cancer
KW - EPIC
KW - IGF
KW - Insulin
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UR - http://www.scopus.com/inward/citedby.url?scp=34250321324&partnerID=8YFLogxK
U2 - 10.1002/ijc.22697
DO - 10.1002/ijc.22697
M3 - Article
C2 - 17372899
AN - SCOPUS:34250321324
VL - 121
SP - 368
EP - 376
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
ER -