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SNP rs2071095 in LincRNA H19 is associated with breast cancer risk

Breast Cancer Research and Treatment volume 171, pages 161–171 (2018)Cite this article

Abstract

Purpose

An increasing number of long intergenic non-coding RNAs (lincRNAs) appear to play critical roles in cancer development and progression. To assess the association between SNPs that reside in regions of lincRNAs and breast cancer risk, we performed a large case-control study in China.

Methods

We carried out a two-stage case-control study including 2881 breast cancer cases and 3220 controls. In stage I, we genotyped 17 independent (r2 < 0.5) SNPs located in 6 tumor-related lincRNAs by using the TaqMan platform. In stage II, SNPs potentially associated with breast cancer risk were replicated in an independent population. Quantitative real-time PCR was used to measure H19 levels in tissues from 228 breast cancer patients with different genotypes.

Results

We identified 2 SNPs significantly associated with breast cancer risk in stage I (P < 0.05), but not significantly replicated in stage II. We combined the data from stage I and stage II, and found that, compared with the rs2071095 CC genotype, AA and CA + AA genotypes were associated with significantly decreased risk of breast cancer (adjusted OR 0.83, 95% CI 0.69–0.99; adjusted OR 0.88, 95% CI 0.80–0.98, respectively). Stratified analyses showed that rs2071095 was associated with breast cancer risk in estrogen receptor (ER)-positive patients (P = 0.002), but not in ER-negative ones (P = 0.332). Expression levels of H19 in breast cancer cases with AA genotype were significantly lower than those with CC genotype.

Conclusions

We identified that rs2071095 may contribute to the susceptibility of breast cancer in Chinese women via affecting H19 expression. The mechanisms underlying the association remain to be investigated.

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Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No.81473039), and the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (No.20140141).

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Affiliations

  1. Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy in Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of China

    Ping Cui, Yanrui Zhao, Xinlei Chu, Hong Zheng, Fengju Song & Kexin Chen

  2. Department of Cancer Biobank, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Centre of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China

    Na He

  3. Department of Epidemiology, Fairbanks School of Public Health, Indiana University Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA

    Jiali Han

Authors
  1. Ping Cui
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  2. Yanrui Zhao
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  3. Xinlei Chu
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  4. Na He
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  5. Hong Zheng
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  7. Fengju Song
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Correspondence to Fengju Song or Kexin Chen.

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The authors declare that they have no conflict of interest.

Ethical approval

We declare that all experiments that we have performed comply with the current laws of our country. All procedures performed in our study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Cui, P., Zhao, Y., Chu, X. et al. SNP rs2071095 in LincRNA H19 is associated with breast cancer risk. Breast Cancer Res Treat 171, 161–171 (2018). https://doi.org/10.1007/s10549-018-4814-y

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Keywords

  • Breast cancer
  • H19
  • LincRNA
  • Genetic susceptibility
  • SNP