Biological Clock Adjustment

Dr.Atilla Engin, MD, phD, Professor of General Surgery

There is a center in the brain that adapts the human body to night/day changes. This center along with many hormonal and metabolic activities during daylight regulates the behaviour of the person as well. Therefore all metabolic conditions become coordinated with the outside environment (Hastings et al.2003). Daylight is first perceived by the retina of the eye that enables us to see (Berson et al.2002) and then the day/night concept is sent to the centers of the body that adjust these changes. The secretion of melatonin which is an anti-cancer hormone is much higher during the night without the repressive effect of daylight (Claustrat et al.2005). The normal blood melatonin level is a chemical message that enables all the cells in the body to perceive that it is night time (Reiter 1991). When days get longer and the exposure to light during the night/day increases, the duration and amount of melatonin secretion decreases. Especially a high exposure to light during the night when working represses the secretion of melatonin during the night. The biological clock adjustment mechanism of the body regulates the secretion of melatonin at night which has an important effect in the development of cancer. However how the biological timing information is sent to the cells and the effect of the timing control cells on this process has only been recently acknowledged (Blask et al.2011). Long periods of exposure to daylight and the chronic exposure of light on those who work night shifts impairs the night/day rhythm of melatonin secretion (Filipski et al.2004). The repression of melatonin secretion at night causes sleep and immunity disorders and also increases the risk of different types of cancers (Blask 2009). It is thought that being exposed to illumination all night long not only represses the secretion of melatonin at night but also increases the risk of breast cancer (Blask et al. 2005). The strongest proof that supports the melatonin effect in breast cancer is that blind women are not sensitive to light exposure and have no changes in their melatonin blood levels, and the risk of breast cancer is 20-25% less than normal women (Coleman and Reiter 1992; Hahn 1991; Kliukene et al. 2001; Verkasalo et al.1999). The anti-cancer effect of melatonin is because of its repressive effect on cell increase. During the night when the melatonin level is normal breast cancer cells do not increase. However when the melatonin level is very high or under the normal level, the effects are different (Hill and Blask 1988). Due to working night shifts or sleeping disorders caused by age, when a person is exposed to excessive light and the melatonin cycle is interrupted, there will be a higher risk in the development of breast cancer and also the possibility of the spreading of a present breast cancer (Mao et al.2012).

While the ovaries are the source of estrogen in the pre-menopausal stage, fat tissues and breast tissue are the source of estrogen after the menopause. Even if the estrogen blood level is low, it is always high in cancerous breast tissue (Masamura and frds.1995). The night melatonin secreted at a normal level affects the breast cancer cells directly and reduces the activities of estrogen synthesized in the breast tissue and estrogen receptors (Cos et al.2006). This relationship between melatonin and estrogen in the breast cancer tissue lowers the estrogen receptors of the normal level melatonin with a regular night/day cycle and therefore causes the development, spreading, metastasis, repression of breast cancer(Hill et al.2009). However the timing genes and proteins which arrange the cell mechanism of the night/day cycle found in normal breast tissue do not exist in breast cancer tissue (Xiang et al.2008).

Most probably one fourth of all breast cancer cases are due to hereditary factors (Lichtenstein et al.2000). Only a small portion are related to risk factors such as early age of menstruation, late age of first pregnancy and late menopause. However research shows that there is a rise in breast cancer in many countries with causes unknown. The turn to the industrial society profile seems to be an important cause in this rise. The risk of breast cancer in industrial countries is 5 times higher compared to developing countries and there are no risk factors in 50% of the patients. However in western countries where life has an uninterrupted 24 hour cycle, more and more people are exposed to more light at work and in their homes and their sleeping patterns are interrupted (Stevens et al.2007; Stevens et al. 2011). The risk of breast cancer is higher in these people as with over exposure to light at night, the secretion of melatonin at night is hindered. Many epidemiological data have shown that breast cancer risk is higher in women who work night shifts. When compared, 814 breast cancer patients and 793 healthy women, in those who work between 7:00 p.m and 9:00 a.m, the risk of breast cancer has increased by 60% parallel to the number of working years and the duration of working at night. Even if they don’t work night shifts, breast cancer risk is 14% higher in women with sleeping disorders at night(Davis et al.2001).

In 2441 breast cancer cases in 78,562 women, 52% of the cases are in women who work night shifts and in those who have been working for over 30 years in night shifts, breast cancer risk in post-menopause is increased by 36% and in pre-menopause by 23% (Schernhammer et al.2001).

In a study published in 2006, 115,022 pre-menopausal nurses who carried no risk of cancer were studied for 12 years and in 1352 of them breast cancer developed. In those who worked rotating night shifts for over 20 years, breast cancer risk was increased (Schernhammer et al.2006). However in Chinese women there has been no determined relation between working night shifts and the risk of breast cancer (Pronk et al.2010). Continuous working in night shifts interrupts the adaptation of the melatonin rhythm in all the workers and the melatonin levels in these people are always lower than those who don’t work night shifts. Research suggests that those who mostly work night shifts should periodically go through a check-up for breast cancer (Franzese and Nigri 2007).

The vital importance of the biological clock adjustment has been proved by the IARC (International Agency for Research on Cancer) that has included working night shifts in the ‘’possible carcinogenics (Group 2A)’’ list.(IARC Working Group on the Evaluation of Carcinogenic Risks to Humans 2010; Costa 2010).

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