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.
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 cancerpatients. OBJECTIVE: To evaluate the contribution of the IGF-1 gene polymorphism to breast cancer risk by genotyping for a polymorphic allele size in breast cancerpatients 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.
Authors: F Canzian; J D McKay; R J Cleveland; L Dossus; C Biessy; S Rinaldi; S Landi; C Boillot; S Monnier; V Chajès; F Clavel-Chapelon; B Téhard; J Chang-Claude; J Linseisen; P H Lahmann; T Pischon; D Trichopoulos; A Trichopoulou; D Zilis; D Palli; R Tumino; P Vineis; F Berrino; H B Bueno-de-Mesquita; C H van Gils; P H M Peeters; G Pera; E Ardanaz; M-D Chirlaque; J R Quirós; N Larrañaga; C Martínez-García; N E Allen; T J Key; S A Bingham; K-T Khaw; N Slimani; T Norat; E Riboli; R Kaaks Journal: Br J Cancer Date: 2006-01-30 Impact factor: 7.640
Authors: Katherine A Bolton; Kelly A Avery-Kiejda; Elizabeth G Holliday; John Attia; Nikola A Bowden; Rodney J Scott Journal: Endocr Connect Date: 2016-04-18 Impact factor: 3.335