People living in regions with high levels of outdoor artificial light at night may face a higher risk of developing thyroid cancer. Over the past century, nightscapes–especially in cities–have drastically changed due to the rapid growth of electric lighting. Also, epidemiological studies have reported an association between higher satellite-measured levels of nighttime light and elevated breast cancer risk. Because some breast cancers may share a common hormone-dependent basis with thyroid cancer, a team led by Qian Xiao, PhD, of The University of Texas Health Science Center at Houston School of Public Health, looked for an association between light at night and later development of thyroid cancer among participants in the NIH-AARP Diet and Health Study, which recruited American adults aged 50 to 71 years in 1995-1996. The investigators analyzed satellite imagery data to estimate levels of light at night at participants’ residential addresses, and they examined state cancer registry databases to identify thyroid cancer diagnoses through 2011.

Among 464,371 participants who were followed for an average of 12.8 years, 856 cases of thyroid cancer were diagnosed (384 in men and 472 in women). When compared with the lowest quintile of light at night, the highest quintile was associated with a 55% higher risk of developing thyroid cancer. The association was primarily driven by the most common form of thyroid cancer, called papillary thyroid cancer, and it was stronger in women than in men. In women, the association was stronger for localized cancer with no sign of spread to other parts of the body, while in men the association was stronger for more advanced stages of cancer. The association appeared to be similar for different tumor sizes and across participants with different sociodemographic characteristics and body mass index. The researchers noted that additional epidemiologic studies are needed to confirm their findings. If confirmed, it will be important to understand the mechanisms underlying the relationship between light at night and thyroid cancer.

The scientists noted that light at night suppresses melatonin, a modulator of estrogen activity that may have important anti-tumor effects. Also, light at night may lead to disruption of the body’s internal clock (or circadian rhythms), which is a risk factor for various types of cancer. Until now, circadian rhythms have not been associated with any type of human tumor, despite the variations in melatonin that could affect almost all tissues. However, it is possible that changes in melatonin may affect certain histotypes rather than others. The animal and human cell types were classified by the Italian pathologist Bizzozero as labile, stable and perennial. The first group includes those cells that are in continuous replacement and renewal (e.g. skin, bone marrow and gastrointestinal mucosa). Stable cells are those that make up a tissue that has a partial capacity for regeneration, such as the liver and some glands. Perennial tissues belong to those that cannot regenerate due to the inability to re-enter the mitotic cycle. For example, muscle cells and neuronal cells belong to this group.

It is generally believed that, due to their replicative potential, labile cells are more susceptible to predisposing oncogenic mutations. As for the stable cells, the mammary and thyroid gland cells belong to this group, but they are also under the influence of powerful hormones that act through nuclear receptors to induce cell proliferation. These glands are also affected by the influence of melatonin; it is no coincidence that breast cancer has been directly related to circadian imbalances. A large experimental evidence exists suggesting the inhibitory action of melatonin on thyroid growth and function; this effect has been revealed by using in vitro experimental models: by chronic and short-term melatonin administration in vivo, by light restriction and by pinealectomy. More recent studies have shown that the opposite is true, namely that thyroid hormones control the synthesis of melatonin, conditioning the expression of the ANAAT (an acetyltransferase) and ASMT (a methyltransferase) enzymes in its biosinthesis.

In cultured thyrocytes, exogenous melatonin increases thyroglobulin expression at mRNA and protein levels on and this effect is not strictly mediated by the upregulation of thyroid transcription factor (TTF1) or other PAX transcription factor family members. The relationship between thyroid cancer and circulating melatonin, therefore it could be probable even if other factors could intervene on the phenomenon. The control of melatonin on immune surveillance is well recognized and the overcoming of cancer cells over this can only occur if the immune defenses are critically lowered. While it is true that melatonin represses thyroid function, its reduction caused by an altered circadian rhythm could increase the risk in subjects predisposed to or carrying a gene mutation in thyroid cells.

• Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

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