Sabina Rinaldi, Rebecca Cleveland, Teresa Norat, Carine Biessy, Sabine Rohrmann, Jakob Linseisen, Heiner Boeing, Tobias Pischon, Salvatore Panico, Claudia Agnoli, Domenico Palli, Rosario Tumino, Paolo Vineis, Petra H M Peeters, Carla H van Gils, Bas H Bueno-de-Mesquita, Alina Vrieling, Naomi E Allen, Andrew Roddam, Sheila Bingham, Kay-Tee Khaw, Jonas Manjer, Signe Borgquist, Vanessa Dumeaux, Inger Torhild Gram, Eiliv Lund, Antonia Trichopoulou, Georgios Makrygiannis, Vassiliki Benetou, Esther Molina, Ignacio Donate Suárez, Aurelio Barricarte Gurrea, Carlos A Gonzalez, Maria-Jose Tormo, Jone M Altzibar, Anja Olsen, Anne Tjonneland, Henning Grønbaek, Kim Overvad, Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Sophie Morois, Nadia Slimani, Paolo Boffetta, Mazda Jenab, Elio Riboli, Rudolf Kaaks
Journal: International journal of cancer 2010;126(7):1702-15
PMID: 19810099
Insulin-like growth factor-I (IGF-1) plays an important role in growth and development as a function of available energy and essential nutrients from body reserves and diet. The aim of the study was to examine the relationships of colorectal cancers with serum levels of IGF-I, and with 2 measures of IGF-binding protein (IGFBP)-3. The study also examined whether relative risks associated to IGF-I levels were modified by anthropometric and dietary factors. A meta-analysis was performed where the study results were combined with the results from previously published prospective studies. For the study, 1,121 case sets with IGF-1 and total IGFBP-3 measurements were observed. For each case participant with colon or rectum cancer, 1 control participant was selected randomly. Control were matched to cases depending on a set criteria. The study found no association between colorectal cancer risk and serum levels of IGF-1 or IGFBP-3. However, the results from the meta-analysis showed only a very mild significant positive association. Overall, findings from the study together with those from the prospective cohort studies indicate a modest role for elevated circulating IGF-I levels in the development of colorectal cancer.
Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I's major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF-I, total and intact IGFBP-3, in a case-control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta-analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF-I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF-I and IGFBP-3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF-I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13-1.93]). Nevertheless, in the meta-analysis a modest positive association remained between serum IGF-I and colorectal cancer risk overall (RR = 1.07 [1.01-1.14] for 1 standard deviation increase in IGF-I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF-I.
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