<i>Period3</i> Structural Variation: A Circadian Biomarker Associated with Breast Cancer in Young Women

Zhu, Yong; Brown, Heather N.; Zhang, Yawei; Stevens, Richard G.; Zheng, Tongzhang

doi:10.1158/1055-9965.268.14.1

Cited by 149 publications

(11 citation statements)

References 21 publications

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“…Some studies support a carcinogenic effect of light exposure at night (Yang et al, 2014), whereas others do not (Dun et al, 2020). Some studies in humans have also found an association between the risk of breast cancer and either the homozygous or heterozygous 5-repeat allele of PER3 (Zhu et al, 2005) or the Ala394Thr polymorphism of the NPAS2 gene (Zhu et al, 2008). However, other analyses which found marginal associations between polymorphisms of ARNTL and CRY1 and breast cancer revealed insignificant results after statistically adjusting for multiple comparisons (Grundy et al, 2013).…”

Section: Physical Healthmentioning

confidence: 99%

Disturbance of the Circadian System in Shift Work and Its Health Impact

2021

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The various non-standard schedules required of shift workers force abrupt changes in the timing of sleep and light-dark exposure. These changes result in disturbances of the endogenous circadian system and its misalignment with the environment. Simulated night-shift experiments and field-based studies with shift workers both indicate that the circadian system is resistant to adaptation from a day- to a night-oriented schedule, as determined by a lack of substantial phase shifts over multiple days in centrally controlled rhythms, such as those of melatonin and cortisol. There is evidence that disruption of the circadian system caused by night-shift work results not only in a misalignment between the circadian system and the external light-dark cycle, but also in a state of internal desynchronization between various levels of the circadian system. This is the case between rhythms controlled by the central circadian pacemaker and clock genes expression in tissues such as peripheral blood mononuclear cells, hair follicle cells, and oral mucosa cells. The disruptive effects of atypical work schedules extend beyond the expression profile of canonical circadian clock genes and affects other transcripts of the human genome. In general, after several days of living at night, most rhythmic transcripts in the human genome remain adjusted to a day-oriented schedule, with dampened group amplitudes. In contrast to circadian clock genes and rhythmic transcripts, metabolomics studies revealed that most metabolites shift by several hours when working nights, thus leading to their misalignment with the circadian system. Altogether, these circadian and sleep-wake disturbances emphasize the all-encompassing impact of night-shift work, and can contribute to the increased risk of various medical conditions. Here, we review the latest scientific evidence regarding the effects of atypical work schedules on the circadian system, sleep and alertness of shift-working populations, and discuss their potential clinical impacts.

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Section: Physical Healthmentioning

confidence: 99%

Disturbance of the Circadian System in Shift Work and Its Health Impact

2021

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“…The human clock gene PER3, located on chromosome 1p36.23, contains a polymorphic domain expressing 4 or 5 copies of a 54-bp tandem repeat sequence (variable number tandem repeat, VNTR) (Zhu et al, 2005). Variation in this sequence has been associated with circadian preference and sleep and mood disorders (Archer et al, 2003(Archer et al, , 2010Ebisawa et al, 2001;Nievergelt et al, 2006;Viola et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Association Study of a Polymorphism in Clock GenePERIOD3and Risk of Inflammatory Bowel Disease

Mazzoccoli

Palmieri

Corritore

et al. 2012

Chronobiology International

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Altered body rhythmicity and deregulated clock gene expression may cause circadian disruption, which can lead to immune dysregulation and chronic inflammatory diseases. PERIOD3 (PER3) polymorphisms have been associated with circadian disruption and changed secretion of cytokines involved in chronic inflammation. Crohn's disease (CD) and ulcerative colitis (UC) are multifactorial diseases resulting from complex interaction among environmental/microbial factors and the intestinal immune system, triggering an abnormal immune response in genetically susceptible individuals. We evaluated the influence of a polymorphism of the clock gene PER3 on susceptibility and behavior of these inflammatory bowel diseases. The rs2797685 variant of the PER3 gene was assessed in 1082 CD and 972 UC patients, 754 of whom had been diagnosed <18 yrs of age, and 1311 unrelated healthy controls. Allele and genotype frequencies of rs2797685 were significantly increased in both CD (p = 1.6 × 10(-4), odds ratio [OR] = 1.38, 95% confidence interval [CI]: 1.17-1.63) and UC (p = .012, OR = 1.25, 95% CI: 1.05-1.48) patients. Difference between frequency distributions remained statistically significant after stratifying the cohort according to age at diagnosis for CD, but not for UC. Statistically significant association was found between PER3 polymorphism and use of immunosuppressive drugs in pediatric CD patients (p < .001) and with stricturing and fistulizing disease behavior in adult CD patients (p = .031). In conclusion, results of this association study suggest a possible role of PER3 polymorphism in determining susceptibility to CD and UC and phenotypic characteristics of CD. In particular, the rs2797685 variant of the PER3 gene is associated with a more aggressive form of CD, highlighted by higher use of immunosuppressants and more frequent stricturing and fistulizing disease behaviors, as well as early onset of CD. This is a descriptive study, and functional data are needed to prove a causal relationship; nonetheless, involvement of the clock gene machinery in the susceptibility and the behavior of inflammatory bowel diseases may suggest new pathophysiological mechanisms and new therapeutic approaches.

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“…7 Immuneering Corp, Cambridge, MA, USA. 8 Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. 9 Bionano Genomics, San Diego CA92121, USA.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…Out of all somatic variants that can be cancer driver events, SVs can be the most challenging to detect using NGS due to the repetitive structure of the human genome [5,6]. Current clinical testing utilizes G-band karyotyping, PCR, and fluorescence in situ hybridization (FISH), all of which are low-throughput technologies that require prior knowledge of the SV's genomic location [7][8][9]. The advent of microarrays has increased throughput, but microarrays lack the base pair resolution to pinpoint the precise start and stop locations of rearrangements [10].…”

Section: Introductionmentioning

confidence: 99%

Structural variant analysis of a cancer reference cell line sample using multiple sequencing technologies

et al. 2022

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Background The cancer genome is commonly altered with thousands of structural rearrangements including insertions, deletions, translocation, inversions, duplications, and copy number variations. Thus, structural variant (SV) characterization plays a paramount role in cancer target identification, oncology diagnostics, and personalized medicine. As part of the SEQC2 Consortium effort, the present study established and evaluated a consensus SV call set using a breast cancer reference cell line and matched normal control derived from the same donor, which were used in our companion benchmarking studies as reference samples. Results We systematically investigated somatic SVs in the reference cancer cell line by comparing to a matched normal cell line using multiple NGS platforms including Illumina short-read, 10X Genomics linked reads, PacBio long reads, Oxford Nanopore long reads, and high-throughput chromosome conformation capture (Hi-C). We established a consensus SV call set of a total of 1788 SVs including 717 deletions, 230 duplications, 551 insertions, 133 inversions, 146 translocations, and 11 breakends for the reference cancer cell line. To independently evaluate and cross-validate the accuracy of our consensus SV call set, we used orthogonal methods including PCR-based validation, Affymetrix arrays, Bionano optical mapping, and identification of fusion genes detected from RNA-seq. We evaluated the strengths and weaknesses of each NGS technology for SV determination, and our findings provide an actionable guide to improve cancer genome SV detection sensitivity and accuracy. Conclusions A high-confidence consensus SV call set was established for the reference cancer cell line. A large subset of the variants identified was validated by multiple orthogonal methods.

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Period3 Structural Variation: A Circadian Biomarker Associated with Breast Cancer in Young Women

Cited by 149 publications

References 21 publications

Disturbance of the Circadian System in Shift Work and Its Health Impact

Disturbance of the Circadian System in Shift Work and Its Health Impact

Association Study of a Polymorphism in Clock GenePERIOD3and Risk of Inflammatory Bowel Disease

Structural variant analysis of a cancer reference cell line sample using multiple sequencing technologies

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