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Olle Melander

Principal investigator

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

Author

  • Jasmine Brandt
  • Signe Borgquist
  • Peter Almgren
  • Asta Försti
  • Linnea Huss
  • Olle Melander
  • Jonas Manjer

Summary, in English

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.

Department/s

  • Surgery
  • Tumor microenvironment
  • Cardiovascular Research - Hypertension
  • Family Medicine and Clinical Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2018-04

Language

English

Pages

1309-1321

Publication/Series

International Journal of Cancer

Volume

142

Issue

7

Document type

Journal article

Publisher

John Wiley and Sons

Topic

  • Cancer and Oncology

Keywords

  • Breast cancer risk
  • Cancer epidemiology
  • Cancer genetics
  • Thyroid hormone
  • Thyroid peroxidase antibodies

Status

Published

Research group

  • Surgery
  • Cardiovascular Research - Hypertension
  • Family Medicine and Clinical Epidemiology

ISBN/ISSN/Other

  • ISSN: 0020-7136