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IGF1 htSNPs in relation to IGF-1 levels in young women from high-risk breast cancer families: implications for early-onset breast cancer

Henningson, Maria LU ; Hietala, Maria LU ; Törngren, Therese LU ; Olsson, Håkan LU and Jernström, Helena LU (2011) In Familial Cancer 10(2). p.173-185
Abstract
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.... (More)
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 40 years 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
BRCA1/2, Insulin-like growth factor-1, Oral contraception, IGF1, polymorphism, IGF1 diplotype, Breast cancer
in
Familial Cancer
volume
10
issue
2
pages
173 - 185
publisher
Kluwer
external identifiers
  • wos:000290937500001
  • scopus:79958113111
ISSN
1389-9600
DOI
10.1007/s10689-010-9404-z
language
English
LU publication?
yes
id
7541eb57-9e16-4dd1-ab8c-0235d139b8a1 (old id 1986005)
date added to LUP
2011-07-01 09:00:04
date last changed
2017-07-09 03:13:20
@article{7541eb57-9e16-4dd1-ab8c-0235d139b8a1,
  abstract     = {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 40 years 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 &lt; 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.},
  author       = {Henningson, Maria and Hietala, Maria and Törngren, Therese and Olsson, Håkan and Jernström, Helena},
  issn         = {1389-9600},
  keyword      = {BRCA1/2,Insulin-like growth factor-1,Oral contraception,IGF1,polymorphism,IGF1 diplotype,Breast cancer},
  language     = {eng},
  number       = {2},
  pages        = {173--185},
  publisher    = {Kluwer},
  series       = {Familial Cancer},
  title        = {IGF1 htSNPs in relation to IGF-1 levels in young women from high-risk breast cancer families: implications for early-onset breast cancer},
  url          = {http://dx.doi.org/10.1007/s10689-010-9404-z},
  volume       = {10},
  year         = {2011},
}