Περίληψη:
Background: Circulating levels of insulin-like growth factor I (IGF-I)
and its main binding protein, IGF binding protein 3 (IGFBP-3), have been
associated with risk of several types of cancer. Heritable factors
explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of
adult twins.
Methods: We systematically examined common genetic variation in 18 genes
in the IGF signaling pathway for associations with circulating levels of
IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP)
were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from
the Breast and Prostate Cancer Cohort Consortium.
Results: After adjusting for multiple testing, SNPs in the IGF1 and
SSTR5 genes were significantly associated with circulating IGF-I (P <
2.1 x 10(-4)); SNPs in the IGFBP3 and IGFALS genes were significantly
associated with circulating IGFBP-3. Multi-SNP models explained R-2 =
0.62% of the variation in circulating IGF-I and 3.9% of the variation
in circulating IGFBP-3. We saw no significant association between these
multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of
prostate or breast cancers.
Conclusion: Common genetic variation in the IGF1 and SSTR5 genes seems
to influence circulating IGF-I levels, and variation in IGFBP3 and
IGFALS seems to influence circulating IGFBP-3. However, these variants
explain only a small percentage of the variation in circulating IGF-I
and IGFBP-3 in Caucasian men and women.
Impact: Further studies are needed to explore contributions from other
genetic factors such as rare variants in these genes and variation
outside of these genes. Cancer Epidemiol Biomarkers Prev; 19(11);
2877-87. (C)2010 AACR.
Συγγραφείς:
Gu, Fangyi
Schumacher, Fredrick R.
Canzian, Federico
Allen,
Naomi E.
Albanes, Demetrius
Berg, Christine D.
Berndt, Sonja
I.
Boeing, Heiner
Bueno-de-Mesquita, H. Bas
Buring, Julie E.
and Chabbert-Buffet, Nathalie
Chanock, Stephen J. and
Clavel-Chapelon, Francoise
Dumeaux, Vanessa
Gaziano, J. Michael
and Giovannucci, Edward L.
Haiman, Christopher A.
Hankinson,
Susan E.
Hayes, Richard B.
Henderson, Brian E.
Hunter, David
J.
Hoover, Robert N.
Johansson, Mattias
Key, Timothy J. and
Khaw, Kay-Tee
Kolonel, Laurence N.
Lagiou, Pagona
Lee, I-Min
and LeMarchand, Loic
Lund, Eiliv
Ma, Jing
Onland-Moret, N.
Charlotte
Overvad, Kim
Rodriguez, Laudina
Sacerdote,
Carlotta
Sanchez, Maria-Jose
Stampfer, Meir J.
Stattin, Par
and Stram, Daniel O.
Thomas, Gilles
Thun, Michael J. and
Tjonneland, Anne
Trichopoulos, Dimitrios
Tumino, Rosario and
Virtamo, Jarmo
Weinstein, Stephanie J.
Willett, Walter C. and
Yeager, Meredith
Zhang, Shumin M.
Kaaks, Rudolf
Riboli, Elio
and Ziegler, Regina G.
Kraft, Peter
