Abstract
Increased breast cancer risk has been reported in some night shift (NS) workers but underlying biological mechanisms are still unclear. We assessed the association between NS work and DNA methylation of tumor suppressor (TP53, CDKN2A, BRCA1, BRCA2) and estrogen receptor (ESR1, ESR2) genes, methylation of repetitive elements (LINE-1, Alu), and telomere length (TL). Forty six female nurses employed in NS for at least two years were matched by age (30–45 years) and length of service (≥1 year) with 51 female colleagues not working in NS. Each subject underwent a semi-structured interview and gave a blood sample. We applied linear regression and spline models adjusted for age, BMI, smoking habit, oral contraceptive use, parity and marital status/age at marriage. Currently working in NS was associated with ESR1 hypomethylation (β: −1.85 (95%CI: −3.03; −0.67), p = 0.003). In current and former NS workers we observed TP53 (−0.93 (−1.73; −0.12), p = 0.03) and BRCA1 (−1.14 (−1.71; −0.58), p <0.001) hypomethylation. We found an increase between TL and number of years in NS in subjects employed in NS <12 years (0.06 (0.03; 0.09), p <0.001), while a decrease if employed in NS ≥12 years (−0.07 −0.10; −0.04), p <0.001). Our findings show NS-associated markers potentially involved in cellular aging, genomic instability, and cancer development.
Highlights
Shift work which causes circadian disruption has been classified as “probably carcinogenic to humans” (Group 2A) by the International Agency for Research on Cancer (IARC) [1], on the basis of limited evidence in humans
Most epidemiological studies considered in IARC evaluation examined breast cancer risk, with the most relevant evidence coming from two prospective cohort studies that showed an increased risk in a subgroup of female nurses after over 20–30 years of rotating night shift work [2,3]
We modeled the variable number of years in night shifts” (NYNS) as a linear spline allowing the slope of the function to change at 12 years: we observed an increase in telomere length in subjects having worked in night change at 12 years: we observed an increase in telomere length in subjects having worked in night shifts for less than 12 years (β = 0.06, 95%CI: 0.03 ; 0.09, p
Summary
Shift work which causes circadian disruption has been classified as “probably carcinogenic to humans” (Group 2A) by the International Agency for Research on Cancer (IARC) [1], on the basis of limited evidence in humans. Most epidemiological studies considered in IARC evaluation examined breast cancer risk, with the most relevant evidence coming from two prospective cohort studies that showed an increased risk in a subgroup of female nurses after over 20–30 years of rotating night shift work [2,3]. Several other investigations have been published since, most of which collectively indicate a tendency of increased risk of breast cancer, especially in workers employed in night shifts for several years [4] or in schedules characterized by many consecutive night shifts [5]. Public Health 2019, 16, 2292; doi:10.3390/ijerph16132292 www.mdpi.com/journal/ijerph
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