Shift-work and Health

Transcription

1 Shift-work and Health Johnni Hansen, Ph.D. Institute of Cancer Epidemiology Danish Cancer Society Copenhagen, Denmark UICC 2010, China

2 Working hours in the European Union Other than normal time (Monday-Friday from 7 am to 5 pm): 76% Evening work: 36-58% Night work: 18-24% Permanent night 7% Source: European Union Commission, 2005

3 Shift-work definition Broad definition: Working outside Monday-Friday 7am to 5pm Probably no major health implications! Night-shift work: Working over midnight or early morning Many potential health implications!

4 Characteristics of day and night workers in the UK (million women study) Characteristic Never night (36,155) Ever night (N=5,497) University/College degree 34.7% 24.2% Physical efforts at work 43.0% 63.1% Divorced in last 5 yerears 2.8% 4.0% Number of children BMI (mean kg/m2) Current smoking 6.2% 8.6% Alcoholic drinks per week In contact with families and friends most days 65.9% 70.0% Almost always feel happy 48.5% 47.0% Self-assessed poor overall health Wang et al. SJWEH, 2012

5 Previously, a day was from dusk to down Dusk Down Night All living subjects have for billions of years been biological influenced by this fundamental system

6 All Cells have Circadian Rhythms: An ancient effect adopted to the 24 hours solar day Endogenous, self-sustained ~24-hour oscillation in biochemistry, physiology, or behavior Entrainment by environmental cycles of light Adjusted to 24 hours each day Takahashi, Annu Rev Neurosci, 18:531, 1995

7 Edison s incandescent bulb (1879)

8 In the modern world, cities are fully lit at night and very bright Times Square, New York City

9 Europe by night.

10 The Biologic Master Clock circadian rhythms

11 Melatonin production during a normal night "day life"

12 Plasma Melatonin (pg/ml) Melatonin Rhythm lux 35 light level p.m. midnight a.m. McIntyre et al, Lancet, 335:488, 1990

13 Phase shift ( reset ) "day life" "night life"

14 The Circuit of a day

15 One Body, many Clocks Bray & Young. Obes Rev, 2009

16 Light-at-night causes: Suppression of melatonin Phase shift of the circadian clock mechanisms: internal and external desynchronization Sleep deprivation with: Neuro-endocrine changes Immune suppression Overall this may increase risk of cancer and CVD

17 Shift-work and health Acute Sleep disruption + deprivation Sleepiness/fatigue at work Injuries Increasing waight (BMI) Fractures at hip and wrist Increased sick leave Social and family problems Chronic Cardiovascular diseases Peptic ulcer Impaired fetal growth Diabetes Ischemic stroke Hypertension Endometriosis Psoriasis Cancer FOHNEU, Tarragona 2012

18 Mechanisms by which shift-work may cause cancer Night shift-work Light at night Phase shift Sleep disruption Epigenetic changes Lifestyle changes Melatonin suppression Physological disruption Stress axis activation DNA Methylation Alcohol, tobacco Diet, physical activity Less Sunshine Vitamin D Anti cancer effects Intracellular disruption Immune suppression Changed expression of circadian genes Metabolic changes Anti cancer effects CANCER

19 Cancer in humans 8 studies on BC Limited evidence in humans for the carcinogenicity (BC) of shiftwork that involves night work Cancer in experimental animals 55 studies Sufficient evidence in experimental animals for the carcinogenicity of light during the daily dark period (biological night) Mechanistic data Mechanisms in animals are highly likely to be operative in humans! Overall evaluation Shiftwork that involves circadian disruption is probably carcinogenic to humans (2A)

20 Cancer in experimental animals No other exposure Chemical initiation / promotion Tumour cell transplantation studies Total Alterations in light exposures 2 / 3 5 / 6 10 / / 19 Chronic experimental jet-lag / 2 2 / 2 SCN lesions / 1 1 / 1 Pinealectomy - 2 / 8 11 / / 21 Effect of physiological concentrations of melatonin / 5 5 / 5 Clock gene mutations 1 / 1 1 / 2-2 / 3 Circadian timing of carc. adm. - 4 / 4-4 / 4 Total 3 / 4 16/ / / 55

21 Ocular exposure of human-breast-tumour-bearing rats to light during darkness Blask, DE. et al. Cancer Res 2005;65:

22 Ocular exposure of human subjects to light at night Copyright 2005 American Association for Cancer Research Blask, D. E. et al. Cancer Res 2005;65:

23 Night-work and breast cancer risk - IARC evaluation 2007 Study obs *Tynes, *Hansen, *Davis, *Schernhammer, *Schernhammer, *Lie, *O'Leary, *Schwartzbaum, Overall Relative Risk

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26 Breast cancer in female flight attendants Relativ Risk Pukkala et al. (1995), Finland 1.9 ( ) yrs of employment 3.4 ( ) Lynge (1996), Denmark 1.6 ( ) Wartenberg & Stapleton (1998), USA 2.0 ( ) Haldorsen et al. (2001), Norway 1.1 ( ) Rafsson et al. (2001), Iceland 1.5 ( ) Blettner et al. (2002), Germany 1.3 ( ) Reynolds et al. (2003), USA 1.4 ( ) international routes 1.8 ( ) Linnersjo et al. (2003), Switzerland 1.3 ( ) Zeeb et al. (2003), EU 1.1 ( ) Kojo et al. (2005), Finland 1.5 ( ) Studies designed for other purposes than night shiftwork!

27 Other evidence for Light-At-Night and breast cancer risk * Flight attendants (shiftwork and jetlag): RR = 1.8 No shiftwork hypothesis No control for confounders Cosmic radiation Breast cancer in the blind: reduced risk (5/5) Bedroom lighting (2/2) Sleep duration: longer sleep lower risk (2/3) Ecological studies on LAN at population level (3/3) OVERALL: SUPPORT for SHIFTWORK

28 Pesch et al 2010: German workers Post IARC-2007 > 20 years: RR = 2.5 ( ; N=12) Pronk et al. 2010: Shanghai workers No association (first study of non-caucasians) Lie et al. 2011: Norwegian nurses Increased risk by increasing no. of consecutive shifts Hansen et al 2011: Danish Nurses Increasing risk by increasing duration; no risk after evening work only Hansen et al 2012: Danish Military workers Increasing risk by increasing duration; more sun exposure in night workers Menegaux, 2012: France workers Overall increased risk (RR=1.4); highest risk (RR=2.0) when start before 1. pregnancy

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30 Design Study of selected cancers and exposure to radar and other military devices Nested case-cohort study on women employed in the Danish military , born alive breast cancer cases ( ), 899 matched controls Postal questionnaire (28 p.) or interview 67% cases and 61% controls participated

31 Sun bathing habits and day vs. night work (controls) Occasional sun bathing frequency Day workers (N=361) Night workers (N=144) n % n % P- value Never/rare Always/at least once weekly

32 Relative risk (OR) for breast cancer among women in the military by night-work metrics Night work characteristic Cases Control OR* 95% CI j Duration (years) Cumulative (years* frequency) Never Reference p for trend 0.03 Never Reference < > p for trend 0.02 *Adjustments: age, HRT, childbirths, age at menarche, education, sunbathing, tobacco.

33 Relative risk (OR) for breast cancer among women in the Danish military by frequency and duration Night work characteristic Case Control OR* j 95% CI j N=141 N=551 Duration and frequency (per week) Never Reference 1 2 times; all durations times; 1 6 years times; 6 15 years times; 15 years p for trend 0.02 *Adjustments: age, HRT, childbirths, age at menarche, education, sunbathing, tobacco.

34 Risk (OR) of breast cancer by diurnal preference Diurnal preference Cases Controls ORj* 95% CI Morning (57%) 1 Reference Evening (22%) Neither (20%) *Adjustments: night-work, age, HRT, childbirths, age at menarche, education, sun, tobacco.

35 Night work, breast cancer risk and diurnal preference Diurnal preference Cumulative night-shift work Cases Controls (N = 141) (N = 551) OR# 95% CI Morning Never Reference < Evening Never Reference < Neither (morning, evening) Never Reference < *Adjustments: age, HRT, childbirths, age at menarche, education, sunbathing, tobacco

36 Conclusions: # Further support to the hypothesis that night work may increase BC risk (11/14) # No BC effect by 1-2 consequtive shifts # Less sun exposure in night-workers may not explain the increasd BC risk # Diurnal preference seems to be an indicator of BC risk # (Especially) morning types should avoid (longterm) night shift-work

37 Most extreeme exposure: All 14 studies, 2012 Study # IARC 2007 *Tynes, 1996 *Hansen, 2001 *Davis, 2001 *Schernhammer,2001 *Schernhammer,2006 *Lie, 2006 *O'Leary, 2006 *Schwartzbaum,2007 Subtotal obs # PUBLISHED AFTER 2007 *Pesch, *Pronk, *Lie, *Hansen, *Hansen, *Menegaux, Subtotal Overall Relative Risk

38 All 14 studies, nurses and non-nurses Study Non-nurses *Tynes, 1996 *Hansen, 2001 *Davis, 2001 *O'Leary, 2006 *Schwartzbaum,2007 *Pesch, 2009 *Pronk, 2010 *Hansen, 2012 *Menegaux, 2012 Subtotal Nurses *Schernhammer,2001 *Schernhammer,2006 *Lie, 2006 *Lie,2010 *Hansen, 2011 Subtotal obs Overall Relative Risk

39 Existing studies about shiftwork and cancer risk by cancer site A priori cancer site Total no. studies Breast Prostate Colo-rectum 3 (2) 0 1 Endometrium Ovary Skin NHL

40 Prevention IARC recomendations: "In the absence of adequate data on humans, it is biologically plausible and prudent to regard agents for which there is sufficient evidence of carcinogenicity in experimental animals as if they presented a carcinogenic risk to humans."

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42 Evidence based prevention: Expert group, Copenhagen 2011# Restriction of the total number of years working night shift Restricting of the number of consecutive night shifts Reddish light and reduced light intensity during work at night Earlier or more intensive mammography screening among female night shiftwork is not recommended Preventive effects of melatonin supplementation may be a promising avenue Women with earlier or current breast cancer should be given advice not to work night shifts Large studies on the impact of various shift schedules and type of light on circadian rhythms need to be conducted #Source: Bonde, Hansen, Kolstad et al: Work at night and breast cancer - report on evidence-based options for preventive actions. Scand J Work Environ Health 2012;38(4):

43 Shift-work and health, Conclusions: # The best documentation exists for acute effects # Some documentation for CVD # Mounting evidence for breast cancer # Poor documentation for other cancers # Night shift work is unavoidable: more recearch in prevention of chronic diseases is needed

44 The future The 24 hours society is further growing. WHO calls for more research within this topic!