TY - JOUR
T1 - Genetic variation in the growth hormone synthesis pathway in relation to circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3, and breast cancer risk
T2 - Results from the European prospective investigation into cancer and nutrition study
AU - Canzian, Federico
AU - McKay, James D.
AU - Cleveland, Rebecca J.
AU - Dossus, Laure
AU - Biessy, Carine
AU - Boillot, Catherine
AU - Rinaldi, Sabina
AU - Llewellyn, Midge
AU - Chajès, Véronique
AU - Clavel-Chapelon, Françoise
AU - Téhard, Bertrand
AU - Chang-Claude, Jenny
AU - Linseisen, Jakob
AU - Lahmann, Petra H.
AU - Pischon, Tobias
AU - Trichopoulos, Dimitrios
AU - Trichopoulou, Antonia
AU - Zilis, Dimosthenes
AU - Palli, Domenico
AU - Tumino, Rosario
AU - Vineis, Paolo
AU - Berrino, Franco
AU - Bas Bueno-De-Mesquita, H.
AU - Van Gils, Carla H.
AU - Peeters, Petra H M
AU - Pera, Guillem
AU - Barricarte, Aurelio
AU - Chirlaque, Maria Dolores
AU - Quiros, J. Ramon
AU - Larrañaga, Nerea
AU - Martínez-García, Carmen
AU - Allen, Naomi E.
AU - Key, Timothy J.
AU - Bingham, Sheila A.
AU - Khaw, Kay Tee
AU - Slimani, Nadia
AU - Norat, Teresa
AU - Riboli, Elio
AU - Kaaks, Rudolf
PY - 2005/10
Y1 - 2005/10
N2 - Insulin-like growth factor-I (IGF-I) stimulates cell proliferation and can enhance the development of tumors in different organs. Epidemiologic studies have shown that an elevated level of circulating IGF-I is associated to increased risk of breast cancer as well as other cancers. Genetic variants affecting the release or biological action of growth hormone (GH), the main stimulator of IGF-I production, may predict circulating levels of IGF-I and have an effect on cancer risk. We tested this hypothesis with a large case-control study of 807 breast cancer patients and 1,588 matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 22 common single nucleotide polymorphisms in 10 genes involved in GH production and action (GHRH, GHRHR, SST, SSTR1-SSTR5, POU1F1, and GH1), and in parallel, we measured serum levels of IGF-I and IGFBP-3, its major binding protein, in samples of cases and controls. SST and SSTR2 polymorphisms showed weak but statistically significant associations with breast cancer risk. SSTR5 polymorphisms were associated with IGF-I levels, whereas one polymorphism in GHRHR and one in POU1F1 were associated with IGFBP-3 levels. Our conclusion is that common genetic variation in the GH synthesis pathway, as measured by single nucleotide polymorphisms selected in the present study, is not a major determinant of IGF-I and IGFBP-3 circulating levels, and it does not play a major role in altering breast cancer risk.
AB - Insulin-like growth factor-I (IGF-I) stimulates cell proliferation and can enhance the development of tumors in different organs. Epidemiologic studies have shown that an elevated level of circulating IGF-I is associated to increased risk of breast cancer as well as other cancers. Genetic variants affecting the release or biological action of growth hormone (GH), the main stimulator of IGF-I production, may predict circulating levels of IGF-I and have an effect on cancer risk. We tested this hypothesis with a large case-control study of 807 breast cancer patients and 1,588 matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 22 common single nucleotide polymorphisms in 10 genes involved in GH production and action (GHRH, GHRHR, SST, SSTR1-SSTR5, POU1F1, and GH1), and in parallel, we measured serum levels of IGF-I and IGFBP-3, its major binding protein, in samples of cases and controls. SST and SSTR2 polymorphisms showed weak but statistically significant associations with breast cancer risk. SSTR5 polymorphisms were associated with IGF-I levels, whereas one polymorphism in GHRHR and one in POU1F1 were associated with IGFBP-3 levels. Our conclusion is that common genetic variation in the GH synthesis pathway, as measured by single nucleotide polymorphisms selected in the present study, is not a major determinant of IGF-I and IGFBP-3 circulating levels, and it does not play a major role in altering breast cancer risk.
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U2 - 10.1158/1055-9965.EPI-04-0874
DO - 10.1158/1055-9965.EPI-04-0874
M3 - Article
C2 - 16214911
AN - SCOPUS:26444620298
VL - 14
SP - 2316
EP - 2325
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 10
ER -