title: Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk: a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC).
abstract: Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also suggests a role of ghrelin in cancer development. We conducted a case-control study on 1359 breast cancer cases and 2389 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition, to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with anthropometric measures, circulating insulin growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 and breast cancer risk. Pair-wise tagging was used to select the 15 polymorphisms that represent the majority of common genetic variants across the GHRL and GHSR genes. A significant increase in breast cancer risk was observed in carriers of the GHRL rs171407-G allele (odds ratio: 1.2; 95% confidence interval: 1.0-1.4; P = 0.02). The GHRL single-nucleotide polymorphism rs375577 was associated with a 5% increase in IGF-I levels (P = 0.01). A number of GHRL and GHSR polymorphisms were associated with body mass index (BMI) and height (P between <0.01 and 0.04). The false-positive report probability (FPRP) approach suggests that these results are noteworthy (FPRP < 0.20). The results presented here add to a growing body of evidence that GHRL variations are associated with BMI. Furthermore, we have observed evidence for association of GHRL polymorphisms with circulating IGF-I levels and with breast cancer risk. These associations, however, might also be due to chance findings and further large studies are needed to confirm our results.
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Laure
authors: L
authors: Dossus
authors: James D
authors: JD
authors: McKay
authors: Federico
authors: F
authors: Canzian
authors: Stefan
authors: S
authors: Wilkening
authors: Sabina
authors: S
authors: Rinaldi
authors: Carine
authors: C
authors: Biessy
authors: Anja
authors: A
authors: Olsen
authors: Anne
authors: A
authors: Tjønneland
authors: Marianne U
authors: MU
authors: Jakobsen
authors: Kim
authors: K
authors: Overvad
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Marie-Christine
authors: MC
authors: Boutron-Ruault
authors: Agnes
authors: A
authors: Fournier
authors: Jakob
authors: J
authors: Linseisen
authors: Annekatrin
authors: A
authors: Lukanova
authors: Heiner
authors: H
authors: Boeing
authors: Eva
authors: E
authors: Fisher
authors: Antonia
authors: A
authors: Trichopoulou
authors: Christina
authors: C
authors: Georgila
authors: Dimitrios
authors: D
authors: Trichopoulos
authors: Domenico
authors: D
authors: Palli
authors: Vittorio
authors: V
authors: Krogh
authors: Rosario
authors: R
authors: Tumino
authors: Paolo
authors: P
authors: Vineis
authors: José Ramon
authors: JR
authors: Quirós
authors: Núria
authors: N
authors: Sala
authors: Carmen
authors: C
authors: Martínez-García
authors: Miren
authors: M
authors: Dorronsoro
authors: Maria-Dolores
authors: MD
authors: Chirlaque
authors: Aurelio
authors: A
authors: Barricarte
authors: Fränzel J B
authors: FJ
authors: van Duijnhoven
authors: H B
authors: HB
authors: Bueno-de-Mesquita
authors: Carla H
authors: CH
authors: van Gils
authors: Petra H M
authors: PH
authors: Peeters
authors: Göran
authors: G
authors: Hallmans
authors: Per
authors: P
authors: Lenner
authors: Sheila
authors: S
authors: Bingham
authors: Kay Tee
authors: KT
authors: Khaw
authors: Tim J
authors: TJ
authors: Key
authors: Ruth C
authors: RC
authors: Travis
authors: Pietro
authors: P
authors: Ferrari
authors: Mazda
authors: M
authors: Jenab
authors: Elio
authors: E
authors: Riboli
authors: Rudolf
authors: R
authors: Kaaks
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D054439:Ghrelin / Q000235:genetics*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054440:Receptors, Ghrelin / Q000235:genetics*
chemical_list: D054439:Ghrelin; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D054440:Receptors, Ghrelin; D007334:Insulin-Like Growth Factor I