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

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Title: 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
Author(s): Barrdahl, M
Canzian, F
Gaudet, MM
Gapstur, SM
Trichopoulou, A
Tsilidis, K
Van Gils, CH
Borgquist, S
Weiderpass, E
Khaw, K-T
Giles, GG
Milne, RL
Le Marchand, L
Haiman, C
Lindstrom, S
Kraft, P
Hunter, DJ
Ziegler, R
Chanock, SJ
Yang, XR
Buring, JE
Lee, I-M
Kaaks, R
Campa, D
Item 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.
Publication Date: 17-Nov-2017
Date of Acceptance: 4-Aug-2017
URI: http://hdl.handle.net/10044/1/57397
DOI: https://dx.doi.org/10.1002/ijc.31145
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.
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.
Keywords: 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
BPC3
breast cancer in situ
genetic epidemiology
single nucleotide polymorphisms
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
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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