Circadian Rhythm Disruption as a Contributor to Racial Disparities in Prostate Cancer

Abstract

In the United States, African American (AA) men have a 2.4 times higher mortality rate due to prostate cancer than White men. The multifactorial causes of the racial disparities in prostate cancer involve various social determinants of health, socioeconomic status, and access to healthcare. However, emerging evidence also suggests that circadian rhythm disruption (CRD) contributes to prostate cancer, and AA men may be more susceptible to developing CRDs. Circadian rhythms play a significant role in metabolism, hormone secretion, and sleep/wake cycles. Disruption in these circadian rhythms can be caused by airplane travel/jetlag, night shift work, exposure to light, and neighborhood noise levels, which can contribute to sleep disorders and chronic conditions such as obesity, diabetes, cardiovascular disease, and depression. The drivers of the racial disparities in CRD include night shift work, racial discrimination, elevated stress, and residing in poor neighborhoods characterized by high noise pollution. Given the increased vulnerability of AA men to CRDs, and the role that CRDs play in prostate cancer, elucidating the clock-related prostate cancer pathways and their behavior and environmental covariates may be critical to better understanding and reducing the racial disparities in prostate cancer.

Circadian Rhythm Sleep-Wake Disorders

“…A longitudinal study of White, Chinese, Black, and Hispanic American adults found that sleep irregularity was greater among Black participants compared to all other groups; greater sleep irregularity was also correlated with greater risks of obesity and hypertension, and increased depression severity and perceived stress 30 . Black individuals in the United States may be at increased risk of circadian rhythm disorders due to occupational, environmental, and health care access–related factors 31 . Risk factors for circadian disruption such as night shift work, exposure to light or noise pollution, and residential segregation (eg, homes closer to highways or factories, overcrowding) and its consequences, including obesity, stress, and sleep deprivation, disproportionately affect Black individuals and may exacerbate existing racial health disparities.…”

“…Black and Hispanic adults are twice as likely to work night shifts compared to White adults. In 2017, the International Agency for Research on Cancer identified rotating shift work, in association with circadian disruption, as a probable human carcinogen, and placed it in the same risk category as ultraviolet radiation, benzo(a)pyrene, and acrylamide 31 …”

“…A longitudinal study found that female nurses who worked night shifts for over 30 years displayed a 36% increased relative risk of breast cancer. Men with a rotating shift schedule have a 20% higher risk of developing prostate cancer compared with those who have a fixed night shift schedule 31 …”

Alterations in Pregnenolone and Testosterone Levels in Male Shift Workers

“…Since epidemiological studies are relatively few in number and are inconsistent, the association between shift work and prostate cancer cannot be confirmed with the available current data [ 30 , 31 , 32 , 33 ]. Several mechanisms have been proposed to explain the possible association between night shift work and prostate cancer risk, including circadian disruption and hormonal alterations [ 33 , 34 , 35 , 36 ].…”

“…Total testosterone travels in the blood mainly bound to proteins, and a small portion circulates as free testosterone. Cortisol levels are a marker of adrenal steroidogenesis since cortisol and testosterone initially share a common pathway involving pregnenolone but which leads to different hormone production [ 34 ] ( Figure 1 ).…”