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Table 1 Genetic associations between circadian clocks and breast cancer

From: Circadian clocks and breast cancer

Mutation/SNP Possible mechanism Phenotype
CLOCK   Self-renewal capacity of mammary progenitor cells becomes compromised (our unpublished data)
Hypermethylation of Clock promoter Mediates CCL5 expression Reduced breast cancer risk [36]
NPAS2 Ala394Thr SNP Altered NPAS2 protein structure Increased breast cancer risk [55]
Per1 deficient Alters expression of checkpoint proteins ATM and Chk2 Increased proliferation [41]
Per1 overexpression Impairs p53 leading to decreased apoptosis, deregulation of c-myc/CyclinD1/Gadd45 Reduces proliferation in colon, lung and breast cancer cell lines [41]
Per2 deficient Increases OCT1 binding to EMT genes Slug, Snail and Twist1 Higher tumour incidence, increased susceptibility to radiation-induced malignant lymphoma [39]
Per2 overexpression Cell cycle arrest, growth inhibition, apoptosis induction Suppresses breast cancer in vivo [40, 41]
Per3 deficient   Higher probability of cancer recurrence [7, 62]
Cry deficient Disrupted cell cycle regulation via de-regulation of Wee-1 and CyclinD1  
BMAL1/Era/Per2 KO Prevents mammary acinar formation Facilitates invasion and metastasis [56]
BMAL1 overexpression Binds to p53 promoter Tumour suppression [61]
  1. Circadian mutations covered in this review and their links to cancer. Both epidemiological and experimental data are included, along with possible mechanisms and resultant phenotypes, where known
  2. KO knockout, SNP single nucleotide polymorphism