Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition

Mazda Jenab, Elio Riboli, Rebecca J. Cleveland, Teresa Norat, Sabina Rinaldi, Alexandra Nieters, Carine Biessy, Ann Tjønneland, Anja Olsen, Kim Overvad, Henning Grønbæk, Françoise Clavel-Chapelon, Marie Christine Boutron-Ruault, Jakob Linseisen, Heiner Boeing, Tobias Pischon, Dimitrios Trichopoulos, Eleni Oikonomou, Antonia Trichopoulou, Salvatore PanicoPaolo Vineis, Franco Berrino, Rosario Tumino, Giovanna Masala, Petra H. Peters, Carla H. Van Gils, H. Bas Bueno-de-Mesquita, Marga C. Ocké, Eiliv Lund, Michelle A. Mendez, María José Tormo, Aurelio Barricarte, Carmen Martínez-García, Miren Dorronsoro, José Ramón Quirós, Göran Hallmans, Richard Palmqvist, Göran Berglund, Jonas Manjer, Timothy Key, Naomi E. Allen, Sheila Bingham, Kay Tee Khaw, Anne Cust, Rudolf Kaaks

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)368-376
Number of pages9
JournalInternational Journal of Cancer
Volume121
Issue number2
DOIs
Publication statusPublished - Jul 15 2007

Fingerprint

Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Protein 1
C-Peptide
Rectal Neoplasms
Colonic Neoplasms
Colorectal Neoplasms
Serum
Neoplasms
Fasting
Logistic Models
Insulin
Hyperinsulinism
Blood Donors
Insulin-Like Growth Factor I
Rectum
Insulin Resistance
Case-Control Studies
Life Style
Carrier Proteins
Colon

Keywords

  • C-peptide
  • Colorectal cancer
  • EPIC
  • IGF
  • Insulin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition. / Jenab, Mazda; Riboli, Elio; Cleveland, Rebecca J.; Norat, Teresa; Rinaldi, Sabina; Nieters, Alexandra; Biessy, Carine; Tjønneland, Ann; Olsen, Anja; Overvad, Kim; Grønbæk, Henning; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie Christine; Linseisen, Jakob; Boeing, Heiner; Pischon, Tobias; Trichopoulos, Dimitrios; Oikonomou, Eleni; Trichopoulou, Antonia; Panico, Salvatore; Vineis, Paolo; Berrino, Franco; Tumino, Rosario; Masala, Giovanna; Peters, Petra H.; Van Gils, Carla H.; Bueno-de-Mesquita, H. Bas; Ocké, Marga C.; Lund, Eiliv; Mendez, Michelle A.; Tormo, María José; Barricarte, Aurelio; Martínez-García, Carmen; Dorronsoro, Miren; Quirós, José Ramón; Hallmans, Göran; Palmqvist, Richard; Berglund, Göran; Manjer, Jonas; Key, Timothy; Allen, Naomi E.; Bingham, Sheila; Khaw, Kay Tee; Cust, Anne; Kaaks, Rudolf.

In: International Journal of Cancer, Vol. 121, No. 2, 15.07.2007, p. 368-376.

Research output: Contribution to journalArticle

Jenab, M, Riboli, E, Cleveland, RJ, Norat, T, Rinaldi, S, Nieters, A, Biessy, C, Tjønneland, A, Olsen, A, Overvad, K, Grønbæk, H, Clavel-Chapelon, F, Boutron-Ruault, MC, Linseisen, J, Boeing, H, Pischon, T, Trichopoulos, D, Oikonomou, E, Trichopoulou, A, Panico, S, Vineis, P, Berrino, F, Tumino, R, Masala, G, Peters, PH, Van Gils, CH, Bueno-de-Mesquita, HB, Ocké, MC, Lund, E, Mendez, MA, Tormo, MJ, Barricarte, A, Martínez-García, C, Dorronsoro, M, Quirós, JR, Hallmans, G, Palmqvist, R, Berglund, G, Manjer, J, Key, T, Allen, NE, Bingham, S, Khaw, KT, Cust, A & Kaaks, R 2007, 'Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition', International Journal of Cancer, vol. 121, no. 2, pp. 368-376. https://doi.org/10.1002/ijc.22697
Jenab, Mazda ; Riboli, Elio ; Cleveland, Rebecca J. ; Norat, Teresa ; Rinaldi, Sabina ; Nieters, Alexandra ; Biessy, Carine ; Tjønneland, Ann ; Olsen, Anja ; Overvad, Kim ; Grønbæk, Henning ; Clavel-Chapelon, Françoise ; Boutron-Ruault, Marie Christine ; Linseisen, Jakob ; Boeing, Heiner ; Pischon, Tobias ; Trichopoulos, Dimitrios ; Oikonomou, Eleni ; Trichopoulou, Antonia ; Panico, Salvatore ; Vineis, Paolo ; Berrino, Franco ; Tumino, Rosario ; Masala, Giovanna ; Peters, Petra H. ; Van Gils, Carla H. ; Bueno-de-Mesquita, H. Bas ; Ocké, Marga C. ; Lund, Eiliv ; Mendez, Michelle A. ; Tormo, María José ; Barricarte, Aurelio ; Martínez-García, Carmen ; Dorronsoro, Miren ; Quirós, José Ramón ; Hallmans, Göran ; Palmqvist, Richard ; Berglund, Göran ; Manjer, Jonas ; Key, Timothy ; Allen, Naomi E. ; Bingham, Sheila ; Khaw, Kay Tee ; Cust, Anne ; Kaaks, Rudolf. / Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition. In: International Journal of Cancer. 2007 ; Vol. 121, No. 2. pp. 368-376.
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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.

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AU - Cust, Anne

AU - Kaaks, Rudolf

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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.

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