Our lives are driven by biological clocks that evolved in concert with natural cycles of light and dark. These clocks control internal processes, including regulation of the cell cycle and DNA repair—all functions important to normal growth—and become out of sync when cancer develops.1
With progressive industrialization, societies have evolved to function 24 hours a day—exposing people to “unnatural” rhythms of light and dark, which could cause detrimental health effects. An estimated 1 in 5 American workers are shift workers, required to be on the job outside the hours of 6 AM to 6 PM.2 Few shift workers get the recommended 7 hours of sleep and are at high risk for sleep disturbances.3,4 In a survey from the Centers for Disease Control and Prevention, 44% of night shift workers and 31.6% of other shift workers reported getting ≤6 hours sleep daily.5 Night workers and those with rotating shifts are almost twice as likely as others to report getting <6 hours of sleep.6
Insufficient sleep is associated with increased risks for many chronic conditions, including obesity and type 2 diabetes, both of which have been linked to higher cancer risk.7-9 The International Agency for Research on Cancer (IARC) has concluded that shift work involving circadian rhythm disruption increases cancer risk and is a probable carcinogen.10,11
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What Connects Shift Work and Cancer?
Circadian disruption related to shift work, rather than the work itself, is the likely mechanism for increased cancer risk, which is most evident among people working night shifts. Leading theories include diminished melatonin activity resulting from exposure to light at night (LAN), related genetic changes, and effects related to sleep deficiencies.11-14
Melatonin
A key circadian hormone, melatonin, is involved in immune system function and inhibition of oncogenesis and tumor growth. It is synthesized and secreted almost solely at night and requires darkness for normal production. Exposure to LAN suppresses melatonin, which may impair its anticancer functions and role in immune system regulation.11,12 Direct connections between LAN exposure and tumor development have been demonstrated in animal studies,1,11,13 and disruption of circadian rhythm in mice is associated with the growth of malignant tumors.11
In experimental conditions of complete darkness, high levels of melatonin suppress growth of existing cancers and protect normal cells from oncogenic transformation.13 There are several mechanisms by which melatonin affects oncogenesis. In animal studies and in-vitro studies of human cancer cell lines, melatonin at physiologic levels inhibits proliferation through regulation of the cell cycle, regulation of estrogen-receptor (ER) expression, and other cellular mechanisms. It suppresses oncogenesis directly through free radical scavenging and indirectly through antioxidative pathways.12 Melatonin plays a role in regulating metabolism of linoleic acid, an essential omega-6 fatty acid found in corn and vegetable oils that predominates in the Western diet and promotes tumor cell growth through up-regulation of ER expression, cell cycle progression, and the MAPK growth cascade. By regulating how cells use linoleic acid, melatonin counteracts its pro-growth effects.12
Nocturnal melatonin levels correlate with levels and balance of immune system cytokines and T lymphocytes. It is theorized that lower levels of lymphocytes (eg, natural killer cells) and cancer-inhibiting Type 1 cytokines (eg, IL-2, INF-ɣ, IL-12) and higher levels of cancer-promoting Type 2 cytokines (IL-4, IL-10) may relate to increased cancer risk.12 Related to breast cancer, melatonin levels may correlate inversely with circulating levels of female sex hormones.11,15
