The International Agency for Research on Cancer, which is part of the World Health Organization, classified shiftwork involves circadian disruption as probably carcinogenic to humans (group 2A) based on sufficient evidence [1]. While night shiftwork is known to increase the risk of breast cancer, but its association with prostate cancer is still controversial [234]. A previous meta-analysis performed suggests that night shiftwork increase the risk of prostate cancer [5]. Another meta-analysis found no obvious association between night shiftwork and prostate cancer, but subgroup analysis suggests that night shiftwork may increase the risk of prostate cancer in Asian men [6]. In a retrospective cohort of rotating shiftwork, a non-statistically significant elevated risk of prostate cancer was reported (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 0.57–5.68) [7]. A population-based case-control study suggests that a long duration of permanent night work in combination with a long shift length or at least 6 consecutive nights may be associated with prostate cancer [8].

Prostate-specific antigen (PSA) is often elevated in prostate disorders, especially prostate cancer. An earlier study revealed a strong positive association with current shiftwork and elevated PSA level at 4.0 ng/mL or greater (OR: 2.62, 95% CI: 1.16–5.95) [9]. This research supports the notion that sleep disturbance or circadian disruption is associated with elevated PSA. Thus, night shift workers likely have an increased risk of developing prostate cancer. But so far, there is only one study that shiftwork increase PSA level. The aim of this study was to investigate whether PSA level was associated with men performing night shiftwork.

The arithmetic mean of serum PSA level was 0.98 ± 0.79 ng/mL. The mean age of the night shift and day shift workers was 46.9 ± 5.5 years and 45.5 ± 7.5 years, respectively. The night shift workers' age was significantly higher than day workers (p < 0.001). The BMI of the night shift workers and day shift workers was 24.9 ± 2.8 and 25.3 ± 3.0, respectively. The night shift workers' BMI was significantly lower than day workers (p = 0.003). The night shift workers showed a higher percentage of smoking, drinking, and regular exercise, which was not statistically significant. Hypertension and diabetes mellitus were not significantly different between the 2 groups (Table 1).

As age increased, PSA levels increased significantly (p < 0.001). The PSA levels were significantly lower in the obese group (BMI ≥ 25) than in the non-obese group (BMI < 25) (p = 0.005). PSA levels were also significantly lower in the regular exercise group than in the group that did not exercise regularly (p = 0.007). There were no significant differences in PSA levels according to smoking, drinking, and night shiftwork. PSA levels were lower in night shift workers compared to day workers, but the difference was not statistically significant. There was still no significant difference after adjusting for the confounders (Table 2). There was no difference in PSA levels according to hypertension and diabetes mellitus in this study. OR and 95% CIs were calculated using a multiple logistic regression analysis, with a PSA of ≥ 4.0 ng/mL as the dependent variable. In all models, the OR was lower in night shift workers but not statistically significant (Table 3).

In this study, PSA levels were lower in night shift workers compared to day workers, but the difference was not statistically significant. There was still no significant difference after adjusting for the confounders. Contrary to previous study, we found no evidence that night shiftwork raises the level of serum PSA. Our results suggest that shiftwork may not have an effect on serum PSA levels.

The epidemiological evidence examining the relationship between night shiftwork and breast cancer is now appreciable. Furthermore, possible association between night shiftwork and prostate cancer was also examined. According to the conclusions of a recently published review article, the evidence for prostate cancer is strong, but still insufficient to allow any firm conclusions to be made [11]. There is still debate, but several studies have shown a significant relationship between prostate cancer and shiftwork [67912131415]. The mechanisms are also unclear, but there are the following hypotheses. According to the potential causality pathway, artificial light at night, reaching the human retina, suppresses nocturnal production of melatonin, an anti-oncogenic agent, resulting in the increased risk of cancer development [16]. Disruption of circadian rhythm is responsible for the loss of regulatory function of cells. Vitamin D deficiency, a decline in immunity due to sleep deprivation, and harmful lifestyle factors (such as poor-quality diets, altered mealtimes, less physical activity, and higher BMI) are suggested as causes [1718]. Sleep deprivation suppresses natural killer-cell activity and changes the T-helper 1/T-helper 2 cytokine balance, reducing cellular immune defense and surveillance. Sleep in the modulation of immunity and demonstrate that even a modest disturbance of sleep produces a reduction of natural immune responses and T cell cytokine production [192021].

Unlike previous studies, we show that PSA was lower in the night shiftwork group. Although we could not determine the exact cause, there are possibilities as to why. First, our results suggest that there may be no association between night shiftwork and prostate cancer, or PSA increasing may not be involved in the mechanism in which night shiftwork causes prostate cancer. Second, the effect of including strong healthy workers could reverse the association between shiftwork and serum PSA level. Those who are vulnerable to health hazards are likely to quit night shiftwork and move to day work. And tire manufacturing is a physically burdensome job. So only physically healthy workers are likely to remain in the production workplace, especially night shiftwork. The average work experience of the subjects in this study exceeded 20 years. It is possible that the surviving workers have been adapted to long-term regular night duty schedules. Shift workers' sleep-wake disturbances can be minimized through ergonomic proper scheduling [22]. Third, occupational and recreational physical activity may help reducing prostate diseases. Physical activity may have an inverse association with prostate cancer and benign prostatic hyperplasia risk [2324]. In this study, PSA levels were also significantly lower in the regular exercise group than in the group that did not exercise regularly. There may have been differences in occupational physical activity between day and shift workers. In the future study, objective evaluation of physical activity may be necessary. Fourth, another reason is the possibility of publication bias. Publication bias is defined as the tendency on the parts of investigators, reviewers, and editors to submit or accept manuscripts for publication based on the direction or strength of the study findings. Publishing only results that show a significant finding disturbs the balance of findings and inserts bias in favor of positive results [25]. It is possible that insignificant studies, such as this study, have not been published. More research results should be accumulated to elucidate the impact of night shiftwork on the prostate.

In this study, PSA levels were significantly low in the younger age group, the obese group, and regular exercise group. These results are consistent with previous studies. As age increases, serum PSA level increases. For every unit increase in age, PSA increased by 0.034 ng/mL [26]. Previous studies have shown an inverse relationship between BMI and PSA level. Lower levels of PSA in obese and overweight men could potentially mask prostate cancer. Evidence suggests that prostate cancer screening by serum PSA may be adversely affected by increased BMI. Higher BMI was associated with higher plasma volume, and hemodilution may therefore be responsible for the lower serum PSA concentrations. High BMI has been directly associated with risk of aggressive or fatal prostate cancer [27282930]. Individuals who engage in more sedentary behavior and lower levels of physical activity have higher PSA concentrations [3132].

The limitations of this study are as follows. First, we could not exclude the effect of unknown confounders in this study. PSA is not cancer specific. Serum PSA levels are also increased in various conditions. The tire manufacturing factory uses a variety of chemical hazards including organic solvents and various rubber components, which many workers are exposed to. Previous studies have shown the possibility of chemical exposure and its association with PSA level. Exposure to either dichloro-diphenyl-trichloroethane or dichloro-diphenyl-dichloroethylene may produce a false-negative PSA test when screening for prostate cancer, resulting in an inaccurate clinical diagnosis. And tetrachlorodibenzodioxin exposure might be associated with more aggressive prostate cancer [3334]. Other confounding variables include the effect of ejaculation or constipation on the serum total PSA, which we did not examine [3536]. Future studies will need to consider detailed occupational and personal information. Owing to the limitations of cross-sectional studies, it was not possible to determine if there was a precise causal relationship. In this study, only about 1% (35 out of 3,195) of the total were those with PSA levels of 4.0 ng/mL or higher. It may not be suitable for performing multiple logistic regression models. Therefore, we attempted various analyses, such as Poisson regression analysis, but could not produce other significant results. And, this study focused exclusively on a specific occupation working in a factory and may not generalize to the entire population. Another limitation is the fact that only the total PSA is measured, and the free PSA is not measured. Use of the percentage of free PSA show better improves the specificity in predicting prostate cancer compared with using total PSA alone [37]. Individual differences in internal time (chronotype) is an important factor in shiftwork research. Chronotype plays a key role in a worker's ability to adjust to night shiftwork [3839]. However, there is a limitation in this study that we did not consider it.

We compared the serum PSA levels of night shift workers and day workers employed in a large manufacturing factory. PSA level was lower in night shift worker compared to the day worker, but it was not statistically significant. Our results suggest that night shiftwork may not influence serum PSA levels. Additional research and consistent results are needed to elucidate the association between night shiftwork and prostate cancer.