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Functional variants in the low-density lipoprotein receptor gene are associated with clear cell renal cell carcinoma susceptibility.

Publication ,  Journal Article
Zhang, G-M; Wang, M-Y; Liu, Y-N; Zhu, Y; Wan, F-N; Wei, Q-Y; Ye, D-W
Published in: Carcinogenesis
December 7, 2017

Recent studies indicate that abnormal levels of low-density lipoprotein (LDL), which is an important component of dyslipidaemia, are associated with alterations to cancer risk, including that of renal cell carcinoma (RCC). Single nucleotide polymorphisms at microRNA-binding sites contribute to cancer susceptibility and progression by affecting the messenger RNA (mRNA) function of target genes. In this case-control study, we examined the frequency of six potentially functional single nucleotide polymorphisms in the LDL receptor gene (LDLR) in 1004 clear cell RCC (ccRCC) patients and 1065 cancer-free subjects. Logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs). The association between genetic variants and levels of LDLR mRNA and protein was also evaluated. Compared with the CC genotype, multivariate logistic regression analysis showed that the LDLR rs2738464 variant GG genotype was associated with a significantly decreased ccRCC risk (P = 0.002, OR: 0.605, 95% CI: 0.439-0.833). Further functional experiments showed that the rs2738464 variant G allele affected miR-330 regulation of the LDLR 3'-untranslated region (UTR), increasing LDLR mRNA levels in patient kidney tissues. These findings suggest that LDLR rs2738464 may affect the affinity of miR-330 binding to the LDLR 3'-UTR, thus regulating LDLR expression and contributing to ccRCC risk.

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Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

December 7, 2017

Volume

38

Issue

12

Start / End Page

1241 / 1248

Location

England

Related Subject Headings

  • Receptors, LDL
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Odds Ratio
  • Middle Aged
  • MicroRNAs
  • Male
  • Kidney Neoplasms
  • Humans
  • Genotype
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, G.-M., Wang, M.-Y., Liu, Y.-N., Zhu, Y., Wan, F.-N., Wei, Q.-Y., & Ye, D.-W. (2017). Functional variants in the low-density lipoprotein receptor gene are associated with clear cell renal cell carcinoma susceptibility. Carcinogenesis, 38(12), 1241–1248. https://doi.org/10.1093/carcin/bgx098
Zhang, Gui-Ming, Meng-Yun Wang, Ya-Nan Liu, Yao Zhu, Fang-Ning Wan, Qing-Yi Wei, and Ding-Wei Ye. “Functional variants in the low-density lipoprotein receptor gene are associated with clear cell renal cell carcinoma susceptibility.Carcinogenesis 38, no. 12 (December 7, 2017): 1241–48. https://doi.org/10.1093/carcin/bgx098.
Zhang G-M, Wang M-Y, Liu Y-N, Zhu Y, Wan F-N, Wei Q-Y, et al. Functional variants in the low-density lipoprotein receptor gene are associated with clear cell renal cell carcinoma susceptibility. Carcinogenesis. 2017 Dec 7;38(12):1241–8.
Zhang, Gui-Ming, et al. “Functional variants in the low-density lipoprotein receptor gene are associated with clear cell renal cell carcinoma susceptibility.Carcinogenesis, vol. 38, no. 12, Dec. 2017, pp. 1241–48. Pubmed, doi:10.1093/carcin/bgx098.
Zhang G-M, Wang M-Y, Liu Y-N, Zhu Y, Wan F-N, Wei Q-Y, Ye D-W. Functional variants in the low-density lipoprotein receptor gene are associated with clear cell renal cell carcinoma susceptibility. Carcinogenesis. 2017 Dec 7;38(12):1241–1248.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

December 7, 2017

Volume

38

Issue

12

Start / End Page

1241 / 1248

Location

England

Related Subject Headings

  • Receptors, LDL
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Odds Ratio
  • Middle Aged
  • MicroRNAs
  • Male
  • Kidney Neoplasms
  • Humans
  • Genotype