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The role of polymorphisms in circadian pathway genes in breast tumorigenesis.

Publication ,  Journal Article
Dai, H; Zhang, L; Cao, M; Song, F; Zheng, H; Zhu, X; Wei, Q; Zhang, W; Chen, K
Published in: Breast Cancer Res Treat
June 2011

Disruption of the circadian rhythm or biological clock, which is regulated by a number of clock genes, including circadian locomotor output cycles kaput (CLOCK), period genes (PERs), and cryptochrome genes (CRYs), is a risk factor for breast cancer. We hypothesized that genetic variation in these clock genes may influence breast cancer risk. To test this hypothesis, we designed a hospital-based study that included 1,538 breast cancer patients and 1,605 healthy controls. We genotyped subjects for five single nucleotide polymorphisms (SNPs) and a length variant of the circadian clock genes and evaluated their associations with breast cancer risk. These polymorphisms were determined by TaqMan allelic discrimination assays and the polymerase chain reaction-restriction fragment length polymorphism method. Univariate logistic regression analysis showed that polymorphisms of the CLOCK and CRY1 genes were associated with breast cancer risk. We found that carriers of the CLOCK CT and combined CT+TT genotypes had a significantly higher risk of breast cancer than carriers of the CC genotype (aOR = 1.35, 95% CI = 1.12-1.63 and aOR = 1.30, 95% CI = 1.09-1.56, respectively). Carriers of the CRY1 GT genotype had a decreased risk of breast cancer (aOR = 0.84, 95% CI = 0.71-0.99). We also observed a lower risk of breast cancer in carriers of the CRY2 CC genotype who were ER-positive than in those who were ER-negative (OR = 0.15, 95% CI = 0.04-0.67). When stratified by the CLOCK genotype, patients with the CLOCK CT/ CRY2 CC genotypes had significantly lower cancer risk than those with the GG genotype (aOR = 0.36, 95% CI = 0.14-0.95). Individuals carrying both the CLOCK CC and PER2 AA genotypes had an increased cancer risk (aOR = 2.28, 95% CI = 1.22-4.26). Our study suggests that genetic variants of the circadian rhythm regulatory pathway genes contribute to the differential risk of developing breast cancer in Chinese populations.

Duke Scholars

Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

June 2011

Volume

127

Issue

2

Start / End Page

531 / 540

Location

Netherlands

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Period Circadian Proteins
  • Oncology & Carcinogenesis
  • Middle Aged
  • Humans
  • Genotype
  • Genetic Predisposition to Disease
  • Female
  • Cryptochromes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dai, H., Zhang, L., Cao, M., Song, F., Zheng, H., Zhu, X., … Chen, K. (2011). The role of polymorphisms in circadian pathway genes in breast tumorigenesis. Breast Cancer Res Treat, 127(2), 531–540. https://doi.org/10.1007/s10549-010-1231-2
Dai, Hongji, Lina Zhang, Mingli Cao, Fengju Song, Hong Zheng, Xiaoling Zhu, Qingyi Wei, Wei Zhang, and Kexin Chen. “The role of polymorphisms in circadian pathway genes in breast tumorigenesis.Breast Cancer Res Treat 127, no. 2 (June 2011): 531–40. https://doi.org/10.1007/s10549-010-1231-2.
Dai H, Zhang L, Cao M, Song F, Zheng H, Zhu X, et al. The role of polymorphisms in circadian pathway genes in breast tumorigenesis. Breast Cancer Res Treat. 2011 Jun;127(2):531–40.
Dai, Hongji, et al. “The role of polymorphisms in circadian pathway genes in breast tumorigenesis.Breast Cancer Res Treat, vol. 127, no. 2, June 2011, pp. 531–40. Pubmed, doi:10.1007/s10549-010-1231-2.
Dai H, Zhang L, Cao M, Song F, Zheng H, Zhu X, Wei Q, Zhang W, Chen K. The role of polymorphisms in circadian pathway genes in breast tumorigenesis. Breast Cancer Res Treat. 2011 Jun;127(2):531–540.
Journal cover image

Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

June 2011

Volume

127

Issue

2

Start / End Page

531 / 540

Location

Netherlands

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Period Circadian Proteins
  • Oncology & Carcinogenesis
  • Middle Aged
  • Humans
  • Genotype
  • Genetic Predisposition to Disease
  • Female
  • Cryptochromes