title: Insulin-like growth factor-1 (IGF1) genotype predicts breast volume after pregnancy and hormonal contraception and is associated with circulating IGF-1 levels: implications for risk of early-onset breast cancer in young women from hereditary breast cancer families.
abstract: BRCA1/2 mutations predispose to early-onset breast cancer, especially after oral contraceptive (OC) use and pregnancy. However, the majority of breast cancers might be due to more prevalent low-penetrance genes, which may also modify the risk in BRCA mutation carriers. The absence of the IGF1 19-repeat allele has been associated with high insulin-like growth factor-1 (IGF-1) levels during OC use. High IGF-1 levels are linked to early-onset breast cancer and larger breast volumes in the general population. The goal of this study was to elucidate the relationships between IGF1 genotype, early-onset breast cancer, breast volume, circulating IGF-1 levels and OC use in a prospective cohort of 258 healthy women < or =40 years old from high-risk breast cancer families. All women completed a questionnaire including information on reproductive factors and OC use. We measured the height, weight, breast volumes and plasma IGF-1 levels. IGF-1 levels were similar among parous and nulliparous women not using OCs. In all, 13% had no IGF1 19-repeat allele. There was an interaction between IGF1 genotype and OC use on IGF-1 levels (P=0.026) in nulliparous women and another interaction between IGF1 genotype and parity on breast volume (P=0.01). Absence of the 19-repeat allele was associated with high IGF-1 levels in nulliparous OC users and with larger breast volumes in parous women and OC users. Incident breast cancers were also more common in women without the 19-repeat allele (log rank P=0.002). Our results suggest that lack of the IGF1 19-repeat allele modifies IGF-1 levels, breast volume and possibly early-onset breast cancer risk after hormone exposure in young high-risk women.
authors.affiliation: Department of Oncology, The Jubileum Institute, Lund University Hospital, Lund SE-221 85, Sweden. Helena.Jemstrom@onk.lu.se
authors.forename: H
authors.initials: H
authors.lastname: Jernström
authors.forename: T
authors.initials: T
authors.lastname: Sandberg
authors.forename: E
authors.initials: E
authors.lastname: Bågeman
authors.forename: A
authors.initials: A
authors.lastname: Borg
authors.forename: H
authors.initials: H
authors.lastname: Olsson
mesh_terms: D017668:Age of Onset; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D003278:Contraceptives, Oral, Hormonal / Q000097:blood*; D017931:DNA Primers; D018572:Disease-Free Survival; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010298:Parity; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000097:blood / Q000453:epidemiology / Q000473:pathology*; D012042:Registries; D013548:Sweden / Q000453:epidemiology
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D003278:Contraceptives, Oral, Hormonal; D017931:DNA Primers; D007334:Insulin-Like Growth Factor I