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Thyroid-associated genetic polymorphisms in relation to breast cancer risk in the Malmö Diet and Cancer Study

Brandt, Jasmine LU ; Borgquist, Signe LU ; Almgren, Peter LU ; Försti, Asta LU ; Huss, Linnea LU ; Melander, Olle LU and Manjer, Jonas LU (2018) In International Journal of Cancer 142(7). p.1309-1321
Abstract

Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population-based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO-Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO-Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast... (More)

Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population-based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO-Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO-Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast cancer patients and 3335 controls. Odds ratios (95% confidence intervals) for high free T4, TPO-Ab positivity, and breast cancer were calculated by logistic regression and adjusted for confounders. We identified one free T4-related SNP (rs2235544, D101 gene) that was significantly associated with both free T4 level and breast cancer risk. There was a suggested association between rs11675434 (TPO gene) and TPO-Ab level, and TPO-Ab-related rs11675434 (TPO), rs3094228 (HCP5), rs1033662 (no registered gene), and rs301806 (RERE) were associated with breast cancer risk. There was an indicated interaction between rs6485050 (no registered gene) and free T4 level in regards to breast cancer risk. This is the first study to suggest an association between thyroid-related SNPs and breast cancer risk. All SNPs have a biological plausibility of being associated with breast cancer risk, and may contribute to the genetic predisposition to breast cancer.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer risk, Cancer epidemiology, Cancer genetics, Thyroid hormone, Thyroid peroxidase antibodies
in
International Journal of Cancer
volume
142
issue
7
pages
1309 - 1321
publisher
John Wiley & Sons
external identifiers
  • scopus:85038224377
ISSN
0020-7136
DOI
10.1002/ijc.31156
language
English
LU publication?
yes
id
5b31407a-8b89-47f6-b59d-de1137c7f8b4
date added to LUP
2018-01-10 14:30:13
date last changed
2018-10-28 13:58:47
@article{5b31407a-8b89-47f6-b59d-de1137c7f8b4,
  abstract     = {<p>Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population-based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO-Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO-Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast cancer patients and 3335 controls. Odds ratios (95% confidence intervals) for high free T4, TPO-Ab positivity, and breast cancer were calculated by logistic regression and adjusted for confounders. We identified one free T4-related SNP (rs2235544, D101 gene) that was significantly associated with both free T4 level and breast cancer risk. There was a suggested association between rs11675434 (TPO gene) and TPO-Ab level, and TPO-Ab-related rs11675434 (TPO), rs3094228 (HCP5), rs1033662 (no registered gene), and rs301806 (RERE) were associated with breast cancer risk. There was an indicated interaction between rs6485050 (no registered gene) and free T4 level in regards to breast cancer risk. This is the first study to suggest an association between thyroid-related SNPs and breast cancer risk. All SNPs have a biological plausibility of being associated with breast cancer risk, and may contribute to the genetic predisposition to breast cancer.</p>},
  author       = {Brandt, Jasmine and Borgquist, Signe and Almgren, Peter and Försti, Asta and Huss, Linnea and Melander, Olle and Manjer, Jonas},
  issn         = {0020-7136},
  keyword      = {Breast cancer risk,Cancer epidemiology,Cancer genetics,Thyroid hormone,Thyroid peroxidase antibodies},
  language     = {eng},
  number       = {7},
  pages        = {1309--1321},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Thyroid-associated genetic polymorphisms in relation to breast cancer risk in the Malmö Diet and Cancer Study},
  url          = {http://dx.doi.org/10.1002/ijc.31156},
  volume       = {142},
  year         = {2018},
}