Insulin-like growth factor I polymorphism and breast cancer risk in Jewish women.
BACKGROUND
Genes that confer mild or moderate susceptibility to breast cancer may be involved in the pathogenesis of sporadic breast cancer, modifying the phenotypic expression of mutant BRCA1/BRCA2 alleles. An attractive candidate is the insulin-like growth factor I, a known mitogen to mammary ductal cells in vivo and in vitro, whose serum levels were reportedly elevated in breast cancer patients.


OBJECTIVE
To evaluate the contribution of the IGF-1 gene polymorphism to breast cancer risk by genotyping for a polymorphic allele size in breast cancer patients and controls.


METHODS
We analyzed allele size distribution of the polymorphic CA repeat upstream of the IGF-I gene in 412 Israeli Jewish women: 268 women with breast cancer (212 sporadic and 56 carriers of either a BRCA1 or BRCA2 mutation), and 144 controls. Genotyping was accomplished by radioactive polymerase chain reaction of the relevant genomic region and size fractionation on polyacrylamide gels with subsequent autoradiography.


RESULTS
Among women with breast cancer, with or without BRCA germline mutations, 196 and 198 basepair alleles were present in 4.7% (25/536 alleles), compared with 9% (26/288) controls (P = 0.02). This difference was more pronounced and significant in the non-Ashkenazi population. Conversely, the smaller size allele (176 bp) was present in the breast cancer group only (3/536, 0.6%).


CONCLUSIONS
The IGF-I polymorphism may serve as a marker for breast cancer risk in the general Jewish population, in particular non-Ashkenazi Jews, but extension and confirmation of these preliminary data are needed.
Figer
Arie
A
Oncology Institute, Sourasky Tel Aviv Medical Center, Tel Aviv, Israel.
Karasik
Yael Patael
YP
Baruch
Ruth Gershoni
RG
Chetrit
Angela
A
Papa
Moshe Z
MZ
Sade
Revital Bruchim Bar
RB
Rizel
Shulamith
S
Friedman
Eitan
E
Riezel
Shulamith
S
D000328:Adult; D000368:Aged; D000483:Alleles; D001345:Autoradiography; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D016009:Chi-Square Distribution; D003627:Data Interpretation, Statistical; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007585:Jews / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
D005819:Genetic Markers; D007334:Insulin-Like Growth Factor I