Polymorphisms in the IGF-1 and IGFBP 3 promoter and the risk of breast cancer.
Binding of IGF-1 to the type I IGF receptor starts a signalling cascade that plays an important role in regulating cell proliferation, differentiation and apoptosis. The interaction between the IGF-1 and its receptor is mainly regulated by a binding protein, IGFBP 3. We studied a CA repeat polymorphism 969 bp upstream of the transcription start site in the IGF-1 gene and an A-202 C polymorphism in the IGFBP 3 gene and tested their association with breast cancer risk using four case-control series with a total of 787 cases and 900 controls. We did not find any association between the breast cancer risk and the IGF-1 repeat length (19 versus non-19) or the IGFBP 3 A-202 C polymorphism in the postmenopausal breast cancer series or in women diagnosed for breast cancer under the age of 50. In the familial breast cancer series we observed a non-significantly increased odds-ratio (OR) in homozygotes for the non-19 alleles of the IGF-1 gene (OR 1.51, 95% CI 0.96-2.39, p=0.07). Similarly, in the familial breast cancer series we detected an increased frequency of the IGFBP 3 -202 C allele carriers (OR 1.50, 95% CI 1.05--2.14, p=0.03). The association was stronger in individuals homozygous for these alleles (OR 3.76, 95% CI 1.44-v-9.81, p=0.006). Thus, the polymorphisms in the IGF-1 and IGFBP 3 genes associated with an increased risk of breast cancer in familial cases carrying the variant alleles.
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. k.wagner@dkfz.de
Kerstin
K
Wagner
Kari
K
Hemminki
Elisabeth
E
Israelsson
Ewa
E
Grzybowska
Magnus
M
Söderberg
Jolanta
J
Pamula
Wioletta
W
Pekala
Helena
H
Zientek
Danuta
D
Mielzynska
Ewa
E
Siwinska
Asta
A
Försti
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008875:Middle Aged; D011044:Poland / Q000453:epidemiology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D018709:Statistics, Nonparametric; D013548:Sweden / Q000453:epidemiology
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I