Beskæftigelsesudvalget 2018-19 (2. samling)
BEU Alm.del Bilag 12
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Carcinogenicity of night shift work
In June, 2019, a Working Group of
27 scientists from 16 countries met at
the International Agency for Research
on Cancer (IARC) in Lyon, France,
to finalise their evaluation of the
carcinogenicity of night shift work.
This assessment will be published in
volume 124 of the IARC Monographs.
1
Night shift work involves work,
including transmeridian air travel,
during the regular sleeping hours of the
general population. The misalignment
or disruption of circadian rhythms
of normal physiology is the most
pronounced effect of night shift work.
Night shift work is essential for
guaranteeing round-the-clock
production and activities. It is
commonly found in health care,
manufacturing, transport, retail, and
services sectors. About 1 in 5 workers
worldwide are engaged in night
shift work; however, definitions,
quality, and extent of data vary
globally. Regulatory approaches for
night shift work and their degree of
implementation also differ across
regions and employment sectors.
In 2007, shift work involving
circadian disruption was classified as
“probably carcinogenic to humans”
(Group 2A), on the basis of sufficient
evidence in experimental animals and
limited evidence of breast cancer in
humans. In this updated evaluation,
the Working Group chose the name
“night shift work” to better describe the
exposure circumstances and to reflect
the main evidence base for the human
cancer studies. The re-evaluation was
motivated by the large number of new,
high-quality epidemiologic studies
including additional cancer sites.
However, the Working Group noted
the considerable variability in the detail
and quality of exposure information
on night shift work reported in these
studies. Exposure information was
more detailed in case-control studies,
including in those nested within
cohorts, than in cohort studies. A
number of occupational, individual,
lifestyle, and environmental factors
might mediate, confound, or moderate
potential cancer risk in night shift
workers.
The Working Group concluded there
was limited evidence that night shift
work causes breast, prostate, and
colorectal cancer. This evaluation was
based on comprehensive searches of
the literature, screening of the studies
using established inclusion criteria, and
evaluation of study quality, including
a standardised review of exposure
assessment. Greater weight was
given to the most informative human
cancer studies based on methodologic
considerations, including study size,
potential selection bias, night work
assessment quality (most notably,
potential for misclassification), and
control for potential confounding
factors. The largest number of
informative studies examined breast
cancer, several examined prostate and
colorectal cancer, while fewer were
done on other cancers.
Most cohort studies, including large
cohorts within the general population
2
and among air crew, did not find a
positive association with ever versus
never working night shifts or by
increasing duration of night shift work.
The Nurses’ Health Study II, a large
cohort study that evaluated breast
cancer risk across a broad age range,
found an elevated risk of breast cancer
in long-duration night workers,
3
which
was also seen in a Swedish cohort study.
The strongest evidence regarding an
association of night shift work and
breast cancer is provided by cohort-
based nested case-control studies
and population-based case-control
studies. The largest case-control study,
4
including more than 6000 breast cancer
cases and corresponding controls
from five countries, incorporated
an extensive exposure assessment
protocol and evaluated detailed
exposure metrics on both duration
and intensity of exposure (eg, number
of night shifts per week). This study
provided evidence for positive
associations between night shift work
and breast cancer risk, particularly
among premenopausal women.
The associations were strongest for
high-intensity, long-duration night
shift work. The variation in findings
between studies could be attributed
to differences in exposure assessment
quality or the inclusion of mainly older
post-employment women in some
cohort studies, such that they might
not be able to determine an effect in
younger women. A small minority
viewpoint was that evidence for breast
cancer was inadequate, with studies of
sufficient quality available in humans
but with inconsistent results. Overall,
the Working Group concluded that a
positive association has been observed
regarding night shift work and breast
cancer; however, given the variability
in findings between studies, bias could
not be excluded as an explanation with
reasonable confidence.
Several studies found positive
associations between night shift work
and prostate cancer risk, particularly
in association with longer duration
of exposures, but in others there was
no, or a very small, increased risk
when examining ever versus never
exposure to night shift work.
5,6
Several
informative studies found some
evidence of positive associations
between colorectal cancer risk and
duration of night shift work. However,
these studies had conflicting findings
related to colorectal cancer subsites
and shift work (night versus rotating)
categories.
7
The Working Group
concluded that, overall, these studies
provide some evidence that night shift
work is positively associated with risk of
prostate and colorectal cancer; however,
because the studies were few in number
and the results lacked consistency,
chance and bias could not be ruled out.
The Working Group found that there
is sufficient evidence in experimental
animals for the carcinogenicity of
alteration in the light–dark schedule.
Lancet Oncol
2019
Published
Online
July 4, 2019
http://dx.doi.org/10.1016/
S1470-2045(19)30455-3
For more on the
IARC
Monographs
see http://
monographs.iarc.fr/
Upcoming meetings
Nov 5–11, 2019, volume 125:
Some industrial chemicals
March 24–31, 2020, volume 126:
Opium
May 26 to June 2, 2020,
volume 127: Some aromatic
amines and related compounds
IARC Monograph Working
Group Members
E M Ward (USA)–Meeting Chair;
D Germolec (USA); M Kogevinas
(Spain); D McCormick (USA);
R Vermeulen (Netherlands)–
Subgroup Meeting Chairs;
V N Anisimov (Russia [unable to
attend]); K J Aronson (Canada);
P Bhatti (Canada); P Cocco (Italy);
G Costa (Italy); D C Dorman (USA);
L Fu (USA); A H Garde (Denmark);
P Guénel (France); J Hansen
(Denmark); M I Härmä (Finland);
K Kawai (Japan); E A Khizkhin
(Russia), A Knutsson (Sweden);
F Lévi (UK); C R C Moreno (Brazil);
E Pukkala (Finland [unable to
attend]); E S Schernhammer
(Austria and USA); R C Travis (UK);
M A Waters (USA);
M G Yakubovskaya (Russia);
H Zeeb (Germany); Y Zhu (USA);
S Zienolddiny (Norway)
Declaration of interests
We declare no competing
interests.
Invited Specialists
None
Representatives
Y Chen, for Health and Safety
Executive (HSE), UK; A Niaudet,
for the French Agency for Food,
Environmental and Occupational
Health and Safety (ANSES)
Declaration of interests
All representatives declare no
competing interests.
Observers
R Carel, for Haifa University,
Israel; D Clarkson-Townsend, for
Emory University, USA; A Forrest,
for the United Fire Fighters of
Winnipeg, Canada; C E Peters, for
the Cumming School of
Medicine, University of Calgary,
Canada; M Rozenberg, for Centre
Léon Bérard, France
www.thelancet.com/oncology
Published online July 4, 2019 http://dx.doi.org/10.1016/PII
1
 BEU, Alm.del - 2018-19 (2. samling) - Bilag 12: Orientering om opdateret vurdering af sammenhængen mellem natarbejde og risiko for kræft
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Declaration of interests
A Forrest declares that his airfare
and hotel costs for the IARC
meeting were paid for by the
Manitoba Professional
Firefighters. All other observers
declare no competing interests.
IARC Secretariat
L Benbrahim-Tallaa; V Bouvard;
W R Diver; F El Ghissassi;
J Girschik; Y Grosse; K Z Guyton;
A L Hall; Z Herceg;
C Marant Micallef; N Olson;
E G Rowan; H Rumgay;
M K Schubauer-Berigan;
M C Turner
Declaration of interests
All secretariat declare no
competing interests.
For the
Preamble to the IARC
Monographs
see https://
monographs.iarc.fr/wp-content/
uploads/2019/01/
Preamble-2019.pdf
For
IARC declarations of
interests
see https://
monographs.iarc.fr/wp-content/
uploads/2019/05/124-
Preliminary-list-Participants.pdf
Disclaimer
The views expressed are those of
the authors and do not
necessarily represent the
decisions, policy, or views of their
respective institutions.
The results of several well-designed
chronic animal bioassays were key
to this evaluation. In one of these
studies, male and female mice of three
C57BL/6J inbred strains (one wild-
type and two genetically engineered)
were exposed to repeated 8-h time
shifts in the light–dark schedule from
4–90 weeks of age. Increased incidences
of hepatocellular carcinoma were seen
in all three strains in comparison with
control mice maintained at a stable
12-h light and 12-h dark schedule.
8
In
another study, exposure to constant
light for a lifetime increased the
incidences of lung adenocarcinoma,
malignant melanoma, and total
tumours in female wild-type CBA
mice in comparison with control mice
maintained at a 12-h light and 12-h dark
schedule.
9
The evaluation was further
supported by positive results in other
studies in rodents exposed to shifts in
the light–dark schedule or continuous
light using carcinogen-induced or
transplantable tumour models.
There is robust evidence in both
humans and experimental animals
that alteration in the light–dark
schedule results in changes in serum
melatonin and in the expression of
core circadian genes. With respect
to key characteristics of carcinogens,
the Working Group found that there
is strong mechanistic evidence in
experimental systems, based on effects
consistent with immunosuppression,
chronic inflammation, and cell proli-
feration. Multiple rodent studies of
alteration of the light–dark schedule
demonstrate immune suppression
in nocturnal rats, mice, and Siberian
hamsters.
10–12
Enhanced inflammation
was seen in rodent studies and models
of inflammatory disease. Altered
tumour glucose metabolism consistent
with the Warburg effect was shown
in female nude rats. A few studies of
changes in the light–dark schedule
directly measured increases in cell
proliferation in transplanted tumours.
Additional studies using inoculated
tumour cells or exposures to carcinogens
in rodents showed effects including
increased tumour growth consistent
with increases in cell proliferation.
Mechanistic studies in night shift
workers were more disparate regarding
the endpoints, study designs, and
results. In exposed humans, the Working
Group found the mechanistic evidence
to be limited, based on suggestive but
inconsistent evidence of alterations in
oestrogen homeostasis in female night
shift workers. In sum, the Working
Group classified night shift work in
Group 2A, “probably carcinogenic to
humans”, based on limited evidence of
cancer in humans, sufficient evidence
of cancer in experimental animals,
and strong mechanistic evidence in
experimental animals.
2
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6
7
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IARC Monographs Vol 124 group
International Agency for Research on
Cancer, Lyon, France
1
International Agency for Research on Cancer.
Volume 124: night shift work. IARC Working
Group. Lyon, France; June 4–11, 2019.
IARC Monogr Eval Carcinog Risk Chem Hum
(in press).
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Night shift work and breast cancer incidence:
three prospective studies and meta-analysis of
published studies.
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2016;
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Rotating night-shift work and the risk of
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Am J Epidemiol
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Night shift work and breast cancer: a pooled
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Eur J Epidemiol
2018;
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and the incidence of prostate cancer: a 10-year
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Barul C, Richard H, Parent ME. Nightshift work
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Canadian case-control study PROtEuS.
Am J Epidemiol
(in press).
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Rotating night shift work and colorectal cancer
risk in the Nurses’ Health Studies.
Int J Cancer
2018;
143:
2709–17.
Kettner NM, Voicu H, Finegold MJ, et al.
Circadian homeostasis of liver metabolism
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Cancer Cell
2016;
30:
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Anisimov VN, Baturin DA, Popovich IG, et al.
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Logan RW, Zhang C, Murugan S, et al.
Chronic shift-lag alters the circadian clock of
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J Immunol
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Castanon-Cervantes O, Wu M, Ehlen JC, et al.
Dysregulation of inflammatory responses by
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J Immunol
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Bedrosian TA, Fonken LK, Walton JC, Nelson RJ.
Chronic exposure to dim light at night
suppresses immune responses in Siberian
hamsters.
Biol Lett
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7:
468–71.
2
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