A strong positive association with shiftwork and elevated prostate-specific antigen (PSA) level was found in an analysis of three National Health and Nutrition Examination Survey (NHANES) studies. “Our data support the notion that sleep or circadian disruption is associated with elevated PSA, indicating that shiftworking men likely have an increased risk of developing prostate cancer,” sleep medicine and public health investigators reported in the Journal of the National Cancer Institute.
“This analysis included 2,017 working men aged 40 to 65 years, which may be extrapolated to represent approximately 31,576,504 men in the United States,” the investigators explained. There were 1,784 nonshiftworkers and 233 shiftworkers, defined as those who worked regular nightshifts or rotating shifts. “Approximately 25% of the United States population is currently engaged in nondaytime or rotating shiftwork,” the investigators noted.
Shiftworkers were slightly younger, less likely to be married and have health insurance, and had lower education and income levels, and a statistically significant shorter average duration of sleep, 6.2 hours vs 6.7 hours for nonshiftworkers (P < .001). The two groups of workers had a similar body mass index (BMI).
A single PSA test was obtained for each of the study participants as part of the NHANES laboratory examination and used to determine total and percentage free PSA.
“Low percentage free PSA has recently been shown to better predict aggressive disease and to improve the specificity in predicting disease compared with using total PSA alone,” the authors explained. “To further evaluate the relationship between shiftwork and PSA level, we created a combined variable to define those with high risk of developing aggressive disease, including only those with percentage of free PSA less than or equal to 25% and total PSA of 4.0 ng/mL or greater compared with those defined as low risk, including only those with percentage free PSA greater than 25% and total PSA less than 4.0 ng/mL.”
Among shiftworkers, 5.6% had a total PSA level of 4.0 ng/mL or greater, compared to 2.8% of nonshiftworkers. Adjusted for age, BMI, race/ethnicity, health insurance, average hours of sleep per night, and months on the current job, the multivariable model odds ratio for having total PSA 4.0 ng/mL or greater among shiftworkers compared to nonshiftworkers was 2.62 (95% CI = 1.16–5.95; P = .02).
“In comparisons of high and low risk for aggressive disease, 5.6% of shiftworkers fell into the high risk category compared with 2.6% of nonshiftworkers,” the authors wrote. Adjusted for age, BMI, race/ethnicity, health insurance, average hours of sleep per night, and months on the current job, the multivariate model odds ratio for having a total PSA result of 4.0 ng/mL or greater and a free PSA result less than or equal to 25% among shiftworkers compared to nonshiftworkers was 3.13 (95% CI = 1.38–7.09; P = .01).
The investigators explained that they also “examined the relationship between shiftwork and PSA values by sextile categories (<1.01, 1.01–2.00, 2.01–3.00, 3.01–4.00, 4.01–10.00, >10.00) that have been shown to be predictive of future prostate cancer development.” Results showed that for men aged 45 years or older with total PSA levels of 1.00 ng/mL or less, the absolute risk of future prostate cancer and mortality was less than 1.6%. “ In contrast, for men with a PSA value of 10.00 ng/mL or greater, the risk of developing prostate cancer was 35% for men aged less than 45 years, 41% for men aged 45 to 49 years, and increased stepwise to 88% for men aged greater than 75 years.
Likewise, the absolute risk of mortality for men with a PSA value of 10.00 ng/mL or greater was 9.8% for men aged less than 45 years, 16% for men aged 45 to years 49, and increased to a peak risk of 52% among men aged 60 to 64 years. Based on these projections, it is likely that a greater proportion of the shiftworkers in our dataset will develop and die from prostate cancer in their lifetimes,” the researchers wrote.
“The World Health Organization categorized shiftwork involving circadian desynchrony as a ‘probable carcinogen’ based on studies of breast cancer risk in female shiftworkers. This study supports the notion that shiftwork may relate to an increased risk in prostate cancer among men,” the authors stated. ■