The GH1/IGF-1 axis polymorphisms and their impact on breast cancer development.
The growth hormone 1/insulin-like growth factor-1 (GH1/IGF-1) axis plays an essential role in the development of the breast by regulating cell proliferation, differentiation and apoptosis. Imbalances within this axis lead to an aberrant signalling and recent research has focussed on the overexpression of these growth factors and their involvement in breast cancer development. The increased understanding of the molecular mechanisms and signalling pathways connected to the GH1/IGF-1 axis has provided important insights into aetiology, prevention and therapy for breast cancer. However, to identify the contribution of the GH1/IGF-1 signalling pathway to cancer risk still remains a challenge since the results of various studies are controversial. Here, we discuss the influence of low-penetrance polymorphisms in the genes along the GH1/IGF-1 axis and their impact on hormone levels and cancer risk, especially breast cancer. We point out what is known about the effects of the variants and show how the interaction of genetic variants affects breast cancer risk.
Wagner
Kerstin
K
Division of Molecular Genetic Epidemiology C050, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany. K.Wagner@dkfz.de
Hemminki
Kari
K
Försti
Asta
A
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone