Tag Archives: melatonin

Rotating night shift work is linked to several diseases

"MoonClouds" by Smatprt - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:MoonClouds.JPG#mediaviewer/File:MoonClouds.JPG
“MoonClouds” by Smatprt – Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons – http://commons.wikimedia.org/wiki/File:MoonClouds.JPG#mediaviewer/File:MoonClouds.JPG

Doing activities and working during the night affects the circadian system, causing sleeping disorders thus severely affecting health.

A large prospective study has been published this month on the American Journal of Preventive Medicine using data from the Nurses’ Health Study (NHS), linking night shift rotation, cardiovascular diseases (CVDs), and some types of cancer mortality1. The NHS was established in 1976 enrolling more than 100,000 nurses aged 30–55 years. Women with previous CVD or cancer or nurses who did not provide information about their shift were excluded from the study; therefore only the information on 74,862 nurses was used during 22 years of follow-up.

The nurses were classified in four groups according to the years of rotating night shift work: never, 1–5, 6–14, and >15 years. Working rotating night shifts for more than five years significantly correlated with all-cause, CVD, in particular ischemic heart disease, and some type of cancer mortality. Lung cancer was the most significantly correlated cause of cancer mortality, followed by colorectal and breast cancers, but overall cancer mortality was not significantly increased in nurses who worked rotating night shift for more than five years. Also lifestyle factors—such as physical activity, dietary habits, and smoking—body mass index, diabetes, cholesterol were considered, but no significant correlations were identified. Women working rotating night shifts tended to be older, be more physically active, drink less alcohol, eat less cereal, and were more likely to have diabetes, hypertension, and hypercholesterolemia than women without night shift work.

Undoubtedly working rotating night shifts disrupts circadian rhythms, causing not only sleeping pattern disorders, but also affecting health. Many studies have correlated night work and exposure to light during nighttime with cardiovascular diseases and cancer, thus the WHO classified night work as a probable carcinogen in 19972,3,4. The molecular mechanism underlying this correlation is not fully known. Circadian rhythms are controlled by melatonin, the hormone produced during nighttime by the pineal gland in the brain. Any disturbance in sleeping pattern, or exposure to light during night affects melatonin production and the pathways controlled by this hormone. Melatonin has been involved in several processes (metabolism, immune response, reproduction, etc.); therefore it is not surprising that this hormone can affect several diseases.

Although in this study only nurses were considered and no other professions, this is the largest prospective cohort available worldwide with a high proportion of women working rotating night shift and with a very long follow-up period, thus making it a reliable collection of data without confounding occupation-related diseases.

Moral of the story: Don’t work during the night!

 

1Total and Cause-Specific Mortality of U.S. Nurses Working Rotating Night Shifts. Gu F, Han J, Laden F, Pan A, Caporaso NE, Stampfer MJ, Kawachi I, Rexrode KM, Willett WC, Hankinson SE, Speizer FE, Schernhammer ES. Am J Prev Med. 2015 Jan 6. pii: S0749-3797(14)00623-0. doi: 10.1016/j.amepre.2014.10.018

2Melatonin, sleep disturbance and cancer risk. Blask DE.Sleep Med Rev. 2009 Aug;13(4):257-64. doi: 10.1016/j.smrv.2008.07.007. Epub 2008 Dec 17. Review.

3Rotating night shifts and risk of breast cancer in women participating in the nurses’ health study.Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA.J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8.

4Carcinogenicity of shift-work, painting, and fire-fighting. Straif K, Baan R, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Altieri A, Benbrahim-Tallaa L, Cogliano V. Lancet Oncol. 2007 Dec;8(12):1065-6.

See also http://damianodemaria.scienceblog.com/80/light-exposure-at-night-induces-resistance-to-therapy-in-breast-cancer/

Light exposure at night induces resistance to therapy in breast cancer

The disruption of melatonin production during the night through light exposure reduces tumor latency and drives resistance to tamoxifen in a model of estrogen receptor positive alpha (ERa+) breast cancer.

http://commons.wikimedia.org/wiki/File:Luz_en_Movimiento.jpg
http://commons.wikimedia.org/wiki/File:Luz_en_Movimiento.jpg

Melatonin is an hormone mainly produced by the pineal gland in the brain and primarily regulates sleeping habits. Its production is light sensitive; therefore, it is produced only in complete darkness, and sleeping in synthetic lights can interfere with its production. Melatonin has also been involved in the regulation of reproduction, timing of ovulation, aging, immune function, and cancer1. In 2001 a study linked night shift rotation with a moderate increase in breast cancer risk2. Studies have shown that melatonin antagonizes the metabolism of linoleic acid, the most prevalent polyunsaturated fatty acid present in the Western diet that upregulates the expression of genes controlling ER expression, cell cycle, and growth.

A group led by Dr. Steven Hill at the Tulane University (Louisiana)3 investigated how disruption of melatonin production influences not only growth but also response to tamoxifen of ERa+ tumors implanted into rats (xenograft). They did two sets of experiments. In the first set they compared animals kept under normal conditions with animals kept under dim light exposure at night (dLEN); in the second set, they compared dLEN mice with dLEN mice supplemented with nighttime melatonin. They found that tumors implanted in the dLEN rats had a shorter latency and a 2.6-fold increase in the growth rate compared with the controls. These tumors were also totally resistant to tamoxifen, whereas the control animals responded to the therapy. The dLED tumors showed high levels of proliferative markers, increased metabolism, and low apoptosis. Strikingly, when the nighttime melatonin was supplemented in the dLEN mice, tumor growth latency was reduced and resistance to tamoxifen was reestablished, with reduction of metabolism, proliferation markers, and increase in apoptosis.

Many studies have shown that melatonin can affect tumor growth in different cancer models, but this is the first study involving melatonin in resistance to therapy. The resistance to tamoxifen is a big problem in the treatment of ER+ breast cancer; about 30% of patients show resistance, and the causes are not totally understood. Strikingly, this research indicates that melatonin disruption affects resistance to therapy, through a molecular mechanism that may involve ER phosphorylation. Several lifestyle habits can influence cancer risk, cancer development, and resistance to therapy—e.g. diet, smoking, exercise. In addition, this report indicates that even sleeping in the darkness might be more beneficial against cancer.

Sleep in the dark!

1Melatonin, sleep disturbance and cancer risk. Blask DE.Sleep Med Rev. 2009 Aug;13(4):257-64. doi: 10.1016/j.smrv.2008.07.007. Epub 2008 Dec 17. Review.

2Rotating night shifts and risk of breast cancer in women participating in the nurses’ health study.Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA.J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8.

3Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer. Dauchy RT, Xiang S, Mao L, Brimer S, Wren MA, Yuan L, Anbalagan M, Hauch A, Frasch T, Rowan BG, Blask DE, Hill SM. Cancer Res. 2014 Aug 1;74(15):4099-110. doi: 10.1158/0008-5472.CAN-13-3156.