caa a22 4500 445331437 CHVBK 20180317142738.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s10689-010-9404-z doi (NATIONALLICENCE)springer-10.1007/s10689-010-9404-z IGF1 htSNPs in relation to IGF-1 levels in young women from high-risk breast cancer families: implications for early-onset breast cancer [Elektronische Daten] [Maria Henningson, Maria Hietala, Therese Törngren, Håkan Olsson, Helena Jernström] High levels of insulin-like growth factor-1 (IGF-1) have been associated with increased risk of developing several types of cancer including breast cancer. A set of nine haplotype tagging SNPs (htSNPs) in the IGF1 gene were associated with IGF-1 levels and prostate cancer in a Swedish population. We aimed to study the nine htSNPs in three haplotype blocks (block1: rs855211, rs35765, rs2162679; block2: rs1019731, rs7956547, rs5742632; and block3 rs2033178, rs7136446, rs6220) combined into diplotypes, and three additional SNPs (rs5742612, rs35765817, rs35455143) in relation to IGF-1 levels, BRCA status, the IGF1 CA-repeat microsatellite, and breast cancer in a population of 325 Swedish women from breast cancer high-risk families. Questionnaire data and blood samples for IGF-1 and genetic analyses were obtained twice during the menstrual cycle from 269 women aged 40years or younger. SNP analyses were also performed in 56 BRCA1/2 mutation carriers. Women (n=14) with any rare variant block1 diplotype had higher odds to be BRCA1 mutation carriers OR 4.1 (95% CI 1.4-12.2), to lack the common IGF1 19 CA-repeat allele OR 33.3 (95% CI 6.6-166.7), and were more likely to develop early-onset breast cancer (Log Rank P<0.001) than women with common block1 diplotypes. In the subgroup of BRCA1 mutation carriers, block1 rare diplotypes were associated with earlier diagnosis (Log Rank P=0.031). No association was found between IGF-1 levels and individual SNPs or diplotypes. If confirmed, these rare diplotypes may identify women with particularly high risk for early-onset breast cancer and this group should be included in forthcoming studies. Springer Science+Business Media B.V., 2010 BRCA1/2 nationallicence Insulin-like growth factor-1 nationallicence Oral contraception nationallicence IGF1 polymorphism nationallicence IGF1 diplotype nationallicence Breast cancer nationallicence IGF1 : Insulin-like growth factor-1 nationallicence htSNPS : Haplotype tagging single nucleotide polymorphisms nationallicence BRCA : Breast cancer associated gene nationallicence ECR : Evolutionary conserved regions nationallicence LD : Linkage disequilibrium nationallicence IGF1R : Type 1 IGF receptor nationallicence IRS1 : Insulin receptor substrate 1 nationallicence IGFBP2 : IGF binding protein 2 nationallicence OCs : Oral contraceptives nationallicence BMI : Body mass index nationallicence Henningson Maria Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, 221 85, Lund, Sweden aut Hietala Maria Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, 221 85, Lund, Sweden aut Törngren Therese Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, 221 85, Lund, Sweden aut Olsson Håkan Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, 221 85, Lund, Sweden aut Jernström Helena Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, 221 85, Lund, Sweden aut Familial Cancer Springer Netherlands 10/2(2011-06-01), 173-185 1389-9600 10:2<173 2011 10 10689 https://doi.org/10.1007/s10689-010-9404-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-010-9404-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Henningson Maria Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, 221 85, Lund, Sweden aut NATIONALLICENCE 700 1- Hietala Maria Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, 221 85, Lund, Sweden aut NATIONALLICENCE 700 1- Törngren Therese Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, 221 85, Lund, Sweden aut NATIONALLICENCE 700 1- Olsson Håkan Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, 221 85, Lund, Sweden aut NATIONALLICENCE 700 1- Jernström Helena Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, 221 85, Lund, Sweden aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/2(2011-06-01), 173-185 1389-9600 10:2<173 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer