Genetic variation of clock genes and cancer risk: a field synopsis and meta-analysis

Benna, Clara; Helfrich‐Förster, Charlotte; Rajendran, Senthilkumar; Monticelli, Halenya; Pilati, Pierluigi; Nitti, Donato; Mocellin, Simone

doi:10.18632/oncotarget.15074

Cited by 62 publications

(66 citation statements)

References 115 publications

(110 reference statements)

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“…A research reported that RORα may also contribute to the effect of an enhancer through binding to and activating the Pcp‐2(L7) gene promoter and structural gene in Purkinje cells . Finally, one study found that RORA rs7164773 SNP was involved in a statistically significant interaction between breast cancer risk and menopausal status . Taken together, these results suggest that RORA may be considered to function as a tumor suppressor gene, and its high expression may contribute to a good prognosis across multiple cancers, including CM.…”

Section: Discussionmentioning

confidence: 96%

Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival

Wang

et al. 2018

Intl Journal of Cancer

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Cutaneous melanoma (CM) is considered as a steroid hormone-related malignancy. However, few studies have evaluated the roles of genetic variants encoding steroid hormone receptor genes and their related regulators (SHR-related genes) in CM-specific survival (CMSS). Here, we performed a pathway-based analysis to evaluate genetic variants of 191 SHR-related genes in 858 CMSS patients using a dataset from a genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC), and then validated the results in an additional dataset of 409 patients from the Harvard GWAS. Using multivariate Cox proportional hazards regression analysis, we identified three-independent SNPs (RORA rs782917 G > A, RORA rs17204952 C > T and DNMT1 rs7253062 G > A) as predictors of CMSS, with a variant-allele attributed hazards ratio (HR) and 95% confidence interval of 1.62 (1.25-2.09), 1.60 (1.20-2.13) and 1.52 (1.20-1.94), respectively. Combined analysis of risk genotypes of these three SNPs revealed a decreased CMSS in a dose-response manner as the number of risk genotypes increased (p < 0.001); however, no improvement in the prediction model was observed (area under the curve [AUC] = 79.6-80.8%, p = 0.656), when these risk genotypes were added to the model containing clinical variables. Our findings suggest that genetic variants of RORA and DNMT1 may be promising biomarkers for CMSS, but these results needed to be validated in future larger studies.

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Section: Discussionmentioning

confidence: 96%

Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival

Wang

et al. 2018

Intl Journal of Cancer

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“…Indeed, genetic variants of human clock genes have been shown to be associated with phenotypic differences, which could allegedly impact on disease processes, including cancer [72]. Moreover, the various biomarker rhythms of circadian function can be differentially altered by disease processes [73].…”

Section: Other Indicators Of Circadian Function Such As Cortisol or mentioning

confidence: 99%

Relevance of a Mobile Internet Platform for Capturing Inter- and Intrasubject Variabilities in Circadian Coordination During Daily Routine: Pilot Study (Preprint)

Komarzynski¹,

Huang²,

Innominato³

et al. 2018

Preprint

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Section: Introductionmentioning

confidence: 99%

“…Several studies have examined associations between circadian genes and different cancer sites, especially breast cancer, while studies on circadian genes in prostate cancer occurrence are scarce. To date, six studies have investigated associations between genetic variants in clock genes and prostate cancer risk . Among those studies, three have only tested this association at the SNP level, while the others also evaluated the association at gene and pathway levels .…”

Section: Introductionmentioning

confidence: 99%

“…Among those studies, three have only tested this association at the SNP level, while the others also evaluated the association at gene and pathway levels . Some polymorphisms of genes involved in circadian rhythms ( PER1 , PER2 , PER3 , CRY1 , CRY2 , CSNK1E , ARNTL , NPAS2 and CLOCK ) have been associated with the occurrence of prostate cancer . The circadian genes most frequently associated with prostate cancer were NPAS2 , CRY1 and CRY2 .…”

Section: Introductionmentioning

confidence: 99%

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Circadian genes and risk of prostate cancer: Findings from the EPICAP study

Wendeu-Foyet

Koudou

Cénée

et al. 2019

Intl Journal of Cancer

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Circadian rhythms regulate several physiological functions and genes controlling the circadian rhythm were found to regulate cell proliferation, cell cycle and apoptosis. Few studies have investigated the role of those circadian genes in prostate cancer occurrence. We aim to investigate the relationship between circadian genes polymorphisms and prostate cancer risk based on data from the EPICAP study, a population‐based case–control study including 1,515 men (732 cases / 783 controls) with genotyped data. Odds Ratios (ORs) for association between prostate cancer and circadian gene variants were estimated for each of the 872 single nucleotide polymorphisms (SNPs) in 31 circadian clock genes. We also used a gene‐based and pathway‐based approach with a focus on the pathway including 9 core circadian genes. Separate analyses were conducted by prostate cancer aggressiveness. The core‐circadian pathway (p = 0.0006) was significantly associated to prostate cancer, for either low (p = 0.002) or high (p = 0.01) grade tumor. At the gene level, we observed significant associations between all prostate cancer and NPAS2 and PER1 after correcting for multiple testing, while only RORA was significant for aggressive tumors. At the SNP‐level, no significant association was observed. Our findings provide additional evidence of a potential link between genetic variants in circadian genes and prostate cancer risk. Further investigation is warranted to confirm these findings and to better understand the biological pathways involved.

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Genetic variation of clock genes and cancer risk: a field synopsis and meta-analysis

Cited by 62 publications

References 115 publications

Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival

Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival

Relevance of a Mobile Internet Platform for Capturing Inter- and Intrasubject Variabilities in Circadian Coordination During Daily Routine: Pilot Study (Preprint)

Circadian genes and risk of prostate cancer: Findings from the EPICAP study

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