Table 6 Human studies on NSW and epigenetic changes

From: Night shift work and breast cancer: from etiopathology to precision risk analysis

NSW Effect

Parameter(s)

Outcome

Year

Ref.

Epigenetic alterations linked to inflammation

DNAme of Alu, IFN-γ, GCR, TNF-α (blood)

↓ Alu, ↓ IFN-γ, ↑ GCR, ↓ TNF-α → inflammation-related DNAme changes

2010

226

Circadian and cancer-related gene methylation

Promoter DNAme of CLOCK, CRY2, ESR1, CDKN2A, MBD2, HDAC2 (blood)

↓ CLOCK, ↑ CRY2, ↑ ESR1/CDKN2A/MBD2/HDAC2 → circadian disruption and BC risk ↑

2011

216

miRNA promoter methylation

DNAme of 31 miRNA promoters (esp. miR-219) (blood)

↑ miR-219 DNAme → ↓ Jak–STAT / NF-κB immune–antitumor signaling → BC risk ↑

2013

228

Imprinted gene methylation alterations

DNAme at 50 CpG sites in 26 imprinted genes (DLX5, IGF2AS, TP73)

Mixed ↑/↓ DNAme → altered imprinting and cancer-related pathways

2013

229

Global and circadian gene hypomethylation

DNAme of circadian genes (PER1–3, CSNK1E/D, CLOCK, ARNTL)

↓ DNAme across circadian and immune/oxidative stress genes → systemic epigenetic dysregulation

2015

214

Tumor-suppressive miRNA silencing (female workers)

DNAme of miR-34b promoter (blood)

↑ miR-34b DNAme → ↓ expression → ↓ antiproliferative/tumor-suppressive activity → BC risk ↑

2015

232

No methylation change in tumor suppressors

Promoter DNAme of BRCA1, BRCA2

No significant change → no detectable epigenetic effect

2017

230

Tumor-suppressor gene hypomethylation

DNAme of ESR1, TP53, BRCA1, LINE-1, Alu

↓ ESR1/TP53/BRCA1, no change in LINE-1/Alu → specific epigenetic disruption

2019

227

Epigenetic age acceleration

DNAm age (PhenoAge) and CpG methylation (ZFHX3, ATXN7)

↑ epigenetic age ( + 3 y), ↓ ZFHX3, ↑ ATXN7 → accelerated aging and circadian disruption

2019

231

Reversible methylation linked to recovery (SWD cases)

DNAme in GRIN2C, CREB1, CAMK2B

↓ DNAme during work, reversible ↑ during recovery → CREB–CaMKII pathway modulation

2021

235

Melatonin-linked circadian gene methylation (female workers)

DNAme of RORA, MTNR1A, PER3

↑ RORA, mixed MTNR1A, ↓ PER3 → circadian disruption and potential BC risk ↑

2022

196

Shift-dependent methylation in circadian genes

DNAme of CSNK1E, NR1D1, ARNTL

↑ CSNK1E (current), ↓ NR1D1 ( ≥ 10 y NSW), ↑ ARNTL ( ≥ 3 consecutive NS/week) → epigenetic shift-pattern dependence

2022

215

Sex-specific DNAme and epigenetic aging

DNAme of CRY2, CSNK1D, RORA, RORC, LIN54, E2F1, ETS1; epigenetic clocks

↑ DNAme in women after 10–16 y NSW; short-term NSW → ↑ epigenetic age (Horvath, Hannum, PhenoAge, GrimAge)

2023

33

HERV and immune gene methylation (female nurses)

DNAme of ERVFRD-1, ERVL, HERV-P, ERVW-1, BIRC2, FLRT3, MIG6, SIRT1

Differential DNA me; effects modified by BMI → inflammation and immune epigenetic modulation

2023

234

  1. NSW night shift work, SWD shift work disorder, DNAme DNA methylation, CpG cytosine–phosphate–guanine site, miRNA microRNA, HERV human endogenous retrovirus, BC breast cancer, BMI body mass index, IFN-γ interferon gamma, TNF-α tumor necrosis factor alpha, GCR glucocorticoid receptor, ESR1 estrogen receptor 1, TP53 tumor protein p53, BRCA1/2, breast cancer gene 1/2, CDKN2A cyclin-dependent kinase inhibitor 2A, MBD2 methyl-CpG binding domain protein 2, HDAC2 histone deacetylase 2, PER1–3 period circadian regulators 1–3, CSNK1D/E casein kinase 1 delta/epsilon ARNTL, BMAL1 CRY2 cryptochrome circadian regulator 2, NR1D1 nuclear receptor subfamily 1, group D, member 1 (REV-ERBα) RORA/RORC RAR-related orphan receptor A/C, ZFHX, zinc finger homeobox 3, ATXN7 ataxin 7, CREB1 cAMP response element-binding protein 1, CAMK2B calcium/calmodulin-dependent protein kinase II beta, GRIN2C glutamate ionotropic receptor NMDA type subunit 2C, MTNR1A melatonin receptor 1A, DLX5 distal-less homeobox 5, IGF2AS insulin-like growth factor 2 antisense RNA, TP73 tumor protein p73, BIRC2 baculoviral IAP repeat-containing protein 2, FLRT3 fibronectin leucine-rich transmembrane protein 3, MIG6 mitogen-inducible gene 6, SIRT1 sirtuin 1, ERVFRD-1 / ERVL / ERVW-1 / HERV-P / ERVE human endogenous retrovirus family elements; NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells, Jak–STAT Janus kinase–signal transducer and activator of transcription pathway; PhenoAge/Horvath/Hannum/ GrimAge, epigenetic aging clocks based on DNA methylation. Arrows indicate direction of change relative to day workers ( ↑ increase; ↓ decrease; → consequential change).