Does “Clock” Matter in Prostate Cancer?

Abstract

The ancient adaptation of a 24-hour circadian clock has profound effect on our daily biochemical, physiologic, and behavioral processes, including the monitoring of sex hormone levels. Although the disruption of the circadian cycle has been implicated in the etiology of hormone-related female breast cancer, few studies have been undertaken to determine if a link exists in the development of the most common cancer type among men whose etiology remains largely unknown: hormone-related prostate cancer. Here, we hypothesize that both altered-lighted environments and genetic variations in genes responsible for maintaining circadian rhythms may result in deregulation of clock-associated biological processes, such as androgen expression, and consequently influence an individual's risk of prostate cancer. There is also a potential for the interaction of genetic variants and exposures, such as evening shift work. Confirmation of this hypothesis will add to our understanding of the role of the circadian clock in prostate tumorigenesis and further facilitate the development of novel risk and prognostic biomarkers for prostate cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(1):3 -5)

Variants in circadian genes and prostate cancer risk: a population-based study in China

“…These results provide the first evidence supporting the circadian gene hypothesis in prostate tumorigenesis. 15 Findings from animal studies support the hypothesis that circadian genes may affect cancer susceptibility. For example, mice with the mutant PER2 gene had impaired DNA damage responses to g-irradiation and were more cancer-prone as compared to their wild type counterparts.…”

“…Because obesity is a major hypothesis for prostate tumorigenesis, [16][17][18][19]30,31 it is plausible that the interplay between circadian genes and metabolic processes such as insulin-action may also contribute to altering prostate cancer risk. An alternative mechanism by which circadian genes may affect the prostate cancer risk (that was not explored in this study) is through their effect on sex hormone levels in serum, in particular androgens, 15 because prostate cancer is a hormone-dependent malignancy. 19 The central circadian clock in the brain influences steroid hormone secretion via the hypothalamic-pituitarygonadal axis.…”

“…14 These findings suggest that the variation in circadian genes may affect the risk of a variety of cancers including that of the prostate. 15 One possible mechanism by which circadian genes may influence prostate cancer risk is through their effect on metabolism and energy balance. In mice with mutated Clock or deleted Bmal1 (a homologue of human ARNTL), gluconeogenesis was suppressed or abolished, respectively.…”

Clock-cancer connection in non-Hodgkin’s lymphoma

“…These observations have suggested a role for circadian rhythms in the etiology of human cancers. The impact of circadian rhythms on hormone regulation could explain the observed role of circadian factors in hormone-related breast and prostate cancers [28,29]. However, little is known about possible molecular mechanisms underlying this clock-cancer connection in NHL.…”

Electric light, particularly at night, disrupts human circadian rhythmicity: is that a problem?

“…Prostate cancer risk may also be affected by circadian disruption for reasons similar to those for breast cancer [103]. The evidence base is far smaller than for breast cancer, but there are some interesting data on circadian gene variants and risk [104], and also epidemiologic data which report a higher risk in shift workers [98].…”