Τίτλος:
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: Results from the European
Prospective Investigation into Cancer and Nutrition Study
Περίληψη:
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.
Συγγραφείς:
Canzian, F
McKay, JD
Cleveland, RJ
Dossus, L
Biessy, C
and Boillot, C
Rinaldi, S
Llewellyn, M
Chajes, V and
Clavel-Chapelon, F
Tehard, B
Chang-Claude, J
Linseisen, J
and Lahmann, PH
Pischon, T
Trichopoulos, D
Trichopoulou, A
and Zilis, D
Palli, D
Tumino, R
Vineis, P
Berrino, F and
Bueno-de-Mesquita, HB
van Gils, CH
Peeters, PHM
Pera, G and
Barricarte, A
Chirlaque, MD
Quiros, JR
Larranaga, N and
Martinez-Garcia, C
Allen, NE
Key, TJ
Bingham, SA
Khaw,
KT
Slimani, N
Norat, T
Riboli, E
Kaaks, R
