In this prospective, population-based cohort study of women in China, we found no evidence of an association between night-shift work and breast cancer risk. The findings were similar regardless of whether the assessment of night-shift work was based on a job exposure matrix or self-reported information.
The designation of night-shift work as a probable cause of cancer by the IARC was primarily based on experimental evidence (1
). In rodents, exposure to light at night reduced nocturnal melatonin concentrations, and removal of the pineal gland has been shown to increase the incidence or progression of (mammary) tumors (1
Relatively few epidemiologic studies have investigated the association between night-shift work and breast cancer. In 2 prospective cohort studies of nurses that incorporated specific questions on night-shift work, investigators reported elevated risks of breast cancer associated with engaging in night-shift work for over 20 years (8
) and over 30 years (9
). In a registry-linked case-control study conducted among nurses, which assigned exposure on the basis of type of hospital department, Lie et al. (10
) also found an elevated risk of breast cancer associated with working night shifts for over 30 years. A population-based case-control study showed a nonsignificant increased risk for engaging in shift work for over 20 years (12
). Findings for shorter durations of shift work are less consistent. Two population-based case-control studies of breast cancer using specific questions on night-shift work showed an elevated risk (13
) and a reduced risk (14
). In a population-based registry-linked case-control study with job exposure matrix assignments of full occupational history, Hansen (15
) reported elevated breast cancer risk among night-shift workers, while a similar study with job exposure matrix assignments at 2 census years did not demonstrate such an association (16
). Lastly, in a case-control study nested within a cohort of shipboard telegraph operators, Tynes et al. (17
) reported a significant trend of increasing breast cancer risk with increasing duration of shift work among women over age 50 years only. Inconsistent findings from these studies may be explained, in part, by variations in definition of shift work and study design, potential recall bias, focus on a single profession versus multiple professions, and incomplete adjustment for confounding factors (1
). A significantly increased incidence of breast cancer in comparison with the general population has also been observed in 6 out of 7 studies of flight attendants (18
). However, those studies lacked information on night-shift work and may have been confounded by exposure to cosmic radiation (1
To our knowledge, this is the first prospective population-based cohort study to have evaluated the role of shift work in cancer risk, allowing the evaluation of a wide range of occupations and socioeconomic groups. The prospective nature of the data collection tended to minimize recall bias, and the stable job histories in this population might have enhanced the accuracy of recall of occupational history. The cohort was large, with an adequate number of cases for studying the main effects of night-shift work. The high response rate reduced potential selection bias. Furthermore, detailed information on other potential risk factors was available for adjustment and exploration of risk in subgroups. Because of the long occupational histories in our cohort (average duration of 29 years), the long-term effects of working night shifts (i.e., for over 20 and over 30 years) could have been explored. However, the prevalences of women reporting having worked night shifts for such durations were relatively low (7% and 3%, respectively).
Another strength of our study was the use of complementary data on shift work based on occupational history (using a job exposure matrix) and self-reported night-shift work history. However, the accurate definition and assessment of relevant exposure remains a major complicating factor when studying night-shift work. It is unclear what aspects of night-shift work, including type, duration, direction, regularity, timing, and light intensity levels, may be associated with cancer. Consequently, inconsistent definitions of night-shift work have been used in epidemiologic studies with respect to the exact time interval to be considered the night shift, the minimum number of night shifts to be studied, and the evaluation of fixed night shifts versus rotating night shifts (3
). Our questionnaire defined night-shift work as “starting work after 10 PM
at least 3 times a month,” which approximately corresponds to the definition “starting work after 7 PM
at least once a week,” which was used in 2 population-based case-control studies (13
). In contrast, the 2 nurse cohort studies only included rotating night shifts (8
). These studies, which were regarded as notable studies in the IARC evaluation (1
), did show a positive association with breast cancer and may indicate that rotating night shifts are more disruptive than regular “fixed” shifts. Our questionnaire did not capture data on rotating versus fixed shifts and other unknown, potentially important aspects of night-shift work. Resulting misclassification of exposures might help to explain the lack of an association in this study and some of the other studies.
When using a job exposure matrix, it is difficult to take into account the frequency or timing of night shifts. The inclusion of all jobs with the potential for night-shift work in a job exposure matrix could also lead to overestimation of the true prevalence of night-shift work. In our study, 44% of the women had worked in jobs that were classified by the job exposure matrix as potentially involving night-shift work, while only 26% reported a history of night-shift work. Since the occupational histories were obtained prior to cancer diagnosis and assignment of night-shift work was conducted without knowledge of case status, the overestimation of exposure probably resulted in nondifferential misclassification of exposure, which generally tends to bias results towards the null. In our study, neither the job exposure matrix nor self-reported night-shift work revealed an association with breast cancer risk.
To our knowledge, this is the first study of night-shift work and breast cancer risk to have been carried out in a non-Western population. Breast cancer incidence rates in China have traditionally been low in comparison with Western countries, because of differences in diet, reproductive factors, and physical activity. Rising breast cancer incidence in China has been attributed to changes in these risk factors associated with the transition to a more “Western” lifestyle (19
). The reason for the lack of an association with breast cancer in this Chinese population remains unclear, although known breast cancer risk factors were carefully evaluated and adjusted for in our analyses. Recent work has shown ethnic variability in circadian “clock” gene variants (21
). These findings raise the possibility of genetic differences in response to night-shift work. Our study cannot rule out this possibility, although the rapid increases in breast cancer incidence with an increasingly Westernized lifestyle suggest similarities in breast cancer etiology among Chinese and Western populations.
In conclusion, this large prospective study did not show an increased risk of breast cancer in relation to night-shift work, adding to the already inconsistent scientific evidence regarding the role of night-shift work in breast cancer development in humans. The inconsistency may be due to limited knowledge on specific aspects of shift work associated with cancer, such as timing, regularity, and light intensity, and suggests that it may be premature to label shift work a probable cause of human cancer.