A comprehensive analysis of polymorphic variants in steroid hormone and insulin-like growth factor-1 metabolism and risk of in situ breast cancer: results from the Breast and Prostate Cancer Cohort Consortium
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin-like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A-rs2382112 (ORhom = 3.05, 95%CI = 1.72–5.44, Phom = 1.47 × 10−4), MAST2-rs12124649 (ORhom = 1.73, 95% CI =1.18–2.54, Phom = 5.24 × 10−3), and INSR-rs10500204 (ORhom = 1.96, 95% CI = 1.44–2.67, Phom=1.68 × 10−5) were associated with increased risk of BCIS; however, only the latter association was significant after correcting for multiple testing. Furthermore, INSR-rs10500204 was more strongly associated with the risk of BCIS than invasive disease in case-only analyses using the homozygous minor versus homozygous major model (ORhom = 1.78, 95% CI = 1.30–2.44, Phom = 3.23 × 10−4). The SNP INSR-rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A-allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further.
Date Issued
2017-11-17
Date Acceptance
2017-08-04
Citation
International Journal of Cancer, 2017, 142 (6), pp.1182-1188
ISSN
0020-7136
Publisher
Wiley
Start Page
1182
End Page
1188
Journal / Book Title
International Journal of Cancer
Volume
142
Issue
6
Copyright Statement
© 2017 UICC. This is the peer reviewed version of the article, which has been published in final form at https://dx.doi.org/10.1002/ijc.31145. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000422753700011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
single nucleotide polymorphisms
breast cancer in situ
BPC3
genetic epidemiology
GENOME-WIDE ASSOCIATION
SUSCEPTIBILITY LOCI
CONFER SUSCEPTIBILITY
COMMON VARIANTS
PML
LEUKEMIA
GENES
5P12
Publication Status
Published
Date Publish Online
2017-11-07