Spiegel - Sephton JNCI 2002 COMMENT

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• Publié par: Erdi
• Nombre de lectures: 18
• Langue: English

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tors for breast cancer that are associated sleep disruption with cancer risk may be
with sleep disruption. For example, our mediated by a number of pathways, in-
laboratory has recently reported, also in cluding, but not limited to, the disrup-
tion of melatonin secretion. There arethe Journal, that loss of normal diurnal
now sufficient data to support the notionvariation in cortisol predicts early mor-
that the loss of normal diurnal variationtality in metastatic breast cancer (3).
in cortisol is another possible mecha-Cortisol normally shows marked diurnal
nism that could account for the observedvariation, peaking in early morning and
association between shift work anddeclining throughout the day. In our
breast cancer incidence.study, patients with flattened salivary
cortisol rhythms or aberrant peaks and DAVID SPIEGEL
troughs suffered earlier mortality. The SANDRA SEPHTON
prognostic effect of cortisol rhythm on
REFERENCESsurvival emerged approximately 1 year
after cortisol assessment and extended at
(1) Schernhammer ES, Laden F, Speizer FE, Wil-
least 7 years after the assessment (3). A lett WC, Hunter DJ, Kawachi I, et al. Rotating
similar association between 24-hour night shifts and risk of breast cancer in women
participating in the nurses’ health study. J Natlrest–activity rhythms and survival has
Cancer Inst 2001;93:1563–8.been noted in patients with colorectal
(2) Davis S, Mirick DK, Stevens RG. Night shift
cancer (4). Furthermore, patients at high
work, light at night, and risk of breast cancer.
risk for primary breast cancer show ab-
J Natl Cancer Inst 2001;93:1557–62.
normal circadian patterns among an ar- (3) Sephton SE, Sapolsky RM, Kraemer HC,
ray of hormones including cortisol (5). Spiegel D. Diurnal cortisol rhythm as a pre-
dictor of breast cancer survival. J Natl CancerSimilar endocrine disturbances have
Inst 2000;92:994–1000.been linked with advancing age and
(4) Mormont MC, Waterhouse J, Bleuzen P, Gi-
with sleep loss in young subjects (6). In
acchetti S, Jami A, Bogdan A, et al. Marked
our study, patient self-reports of sleep
24-h rest/activity rhythms are associated with
disruption were associated with flatten- better quality of life, better response, and
ing of the diurnal cortisol rhythm (3). longer survival in patients with metastatic co-
lorectal cancer and good performance status.There is evidence that the early morning
Clin Cancer Res 2000;6:3038–45.transition from dim to bright light not
(5) Ticher A, Haus E, Ron IG, Sackett-Lundeenonly suppresses melatonin secretion; it
L, Ashkenazi IE. The pattern of hormonal cir-
also induces a marked elevation of cor-
cadian time structure (acrophase) as an asses-
tisol levels (7). Thus, sleep disruption
sor of breast-cancer risk. Int J Cancer 1996;
coupled with exposure to light at night 65:591–3.
may not only suppress the melatonin (6) Van Cauter E, Plat L, Leproult R, Copinschi
G. Alterations of circadian rhythmicity andpeak but may also interfere with the nor-
sleep in aging: endocrine consequences. Hormmal cortisol nadir. Although mere sleepRe: Night Shift Work, Light at
Res 1998;49:147–52.disruption was not associated with el-Night, and Risk of Breast (7) Leproult R, Colecchia EF, L’Hermite-
evated breast cancer risk in the Davis etCancer Baleriaux M, Van Cauter E. Transition from
al. study (2), it is likely that shift work- dim to bright light in the morning induces an
ers have altered diurnal cortisol patterns immediate elevation of cortisol levels. J Clin
Two studies recently published in the engendered through alterations of sleep Endocrinol Metab 2001;86:151–7.
Journal showed that disruption of diur- and nutritional patterns, abnormal photic
NOTESnal sleep–wakefulness rhythms, espe- stimuli, and altered rest–activity cycles.
cially through nighttime shift work, was In addition, the stress incurred from fre- Affiliations of authors: D. Spiegel, Department
associated with higher subsequent breast quent transitions between daytime and of Psychiatry and Behavioral Sciences, Stanford
University School of Medicine, Stanford, CA; S.cancer incidence (1,2). Both of the ar- nighttime shift work should not be over-
Sephton, Department of Psychiatry and Behavioralticles and the accompanying editorial looked. Indeed, chronic sleep debt has
Sciences, University of Louisville School of Medi-cited melatonin suppression as a likely been linked with the disruption of car-
cine, KY.
mediator via reduced suppression of bohydrate metabolism and thyroid hor-
Correspondence to: David Spiegel, M.D., Dept.
ovarian estrogen production due to light mone function, elevation of sympathetic of Psychiatry and Behavioral Sciences, Stanford
exposure during the time when melato- nervous system activity, as well as with University School of Medicine, Stanford, CA
nin would otherwise be highest. It has hypothalamic–pituitary–adrenal axis 94305–5718 (e-mail: [e-mail]; web
address: pstlab.stanford.edu).also been postulated that melatonin dysfunction. Because these effects are
serves as an antioxidant in tumor cells similar to those seen in normal aging, it
and stimulates cytokine release from ac- is reasonable to propose that sleep debt Our interest in the article “Night Shift
tivated T cells. may increase the incidence or severity of Work, Light at Night, and Risk of Breast
The relationship between sleep dis- age-related diseases, including cancer, Cancer” (1) began with the media cov-
ruption and breast cancer risk may alter- by processes similar to those seen with erage of the research in a number of
natively be explained by other risk fac- advancing age. Thus the association of newspapers across the country. Shift
530 CORRESPONDENCE Journal of the National Cancer Institute, Vol. 94, No. 7, April 3, 2002and reduced risk of breast cancer in youngwork is already known to have a nega- over and above that of other workers
women. J Natl Cancer Inst 1994;86:1403–8.must be solidly established. The datative impact on health, work perfor-
mance, and social life (2–5). If this re- displayed in Table 3 show that the study
NOTESyielded 54 night workers in the casesearch (1) is correct, then there is a
group and 37 in the control group. Afurther risk of malignancy, providing the
2 Affiliations of authors: D. Porock, Universitysimple test on these data does notshift work includes sufficient time on
of Missouri Sinclair School of Nursing,reach statistical significance (P>.1).the night shift [no wonder Davis et al.
of Missouri-Columbia; J. Gentry, University ofThere are many possible variables(1) refer to it as the “graveyard shift”].
Wisconsin-Madison Comprehensive Cancer Care
that have a relationship to the develop-The study by Davis et al. (1) is based Center.
ment of breast cancer that were not re-on 1) the link between exposure to es- Correspondence to: Davina Porock, Ph.D., Uni-
ported, for example, ethnicity or socio- versity of Missouri/Columbia, MU Sinclair Schooltrogen and the risk of breast cancer and
economic status (6) and physical of Nursing, S428 Nursing Bldg., Columbia, MO2) the fact that exposure to light at night
65211–2222 (e-mail: [e-mail]).exercise (7). In fact, economic status inincreases exposure to estrogen through
particular may affect the need to workmechanisms associated with the circa-
on the graveyard shift. A statisticallydian rhythm. This is not an illogical train A very thoughtful and thorough edi-
significant difference between the caseof thought. Four studies were cited [ref- torial (1) and two most interesting
patients and control subjects was founderences within (1)], reporting an in- and valuable publications (2,3) focus
for those having worked the graveyardcreased risk of breast cancer in women attention on the role of light and mela-
shift for 5.7 years or more. This may
who work during the night. Of the four tonin production and the risk of breast
indeed show a need to obtain more data
studies, three were conducted in Scandi- cancer.
on this interesting potential risk factor.
navia, a geographic location known for In 1990, our group put forward a
Questions regarding the risks to
its long nights in winter, and two fo- comprehensive hypothesis that one of
women for breast cancer are important,
cused on airline crews, who have greater the most important etiologic factors in
and the need for research that investi-
exposure to cosmic radiation. Further- the increasing rate of cancers is the
gates all possible factors, particularly
more, in the “Discussion” section, Davis change in light exposure that has taken
those that are potentially under a per-
et al. (1) make reference to research that place during the last 100 years (4). The
son’s control, are essential. Neverthe-
found women with bilateral blindness introduction of electric light generally
less, the need for research with robust
had a statistically significantly lower increased the average daily light expo-
data is imperative if the scientific com-
risk of breast cancer, thus supporting the sure by 4–6 hours. The increase in light
munity is to ensure that women have
notion that there is an association be- exposure decreases the amount of time
access to the quality information that
tween light at night and breast cancer that is available for melatonin produc-
they deserve.
risk. tion, which reduces the nonspecific on-
However, in Davis et al. (1), the data costatic effec