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Project Details
Funding Scheme : General Research Fund
Project Number : 474811
Project Title(English) : Night shift work and breast cancer: a case–control study among Hong Kong women 
Project Title(Chinese) : 病例對照研究香港女性夜班作業與乳腺癌的關係 
Principal Investigator(English) : Prof Tse, Lap Ah 
Principal Investigator(Chinese) :  
Department : The Jockey Club School of Public Health and Primary Care
Institution : The Chinese University of Hong Kong
E-mail Address : shelly@cuhk.edu.hk 
Tel : 22528791 
Co - Investigator(s) :
Prof LAO, Xiang Qian
Prof Wang, Xiao-Rong
Prof Yeo, Winnie
Prof Yu, Ignatius Tak-sun
Panel : Biology & Medicine
Subject Area : Medicine, Dentistry & Health
Exercise Year : 2011 / 12
Fund Approved : 476,700
Project Status : Completed
Completion Date : 31-12-2013
Project Objectives :
To investigate the relationship between night shift work and the risk of breast cancer among Chinese women in Hong Kong.
To explore the interactions which could exist between night shift work and several major risk factors, including menopausal status, light-at-night, sleep deprivation, residential pesticides, occupational exposures to potential EDCs, diet, smoking, alcohol drinking, and family cancer history.
However, we have to reduce sample size from the originally proposed 1066 cases and 1066 controls to 700 subjects in each group due to limited budget obtained (our originally proposed budget has been cut down by 58.8%). We re-estimated sample size using a relatively conservative approach, 636 cases and an equal number of controls will be recruited in order to detect the risk of a modest size of 1.45 for exposures with prevalence rates about 18% to reach a reasonable power of 80% at the 5% significance level (one-sided). To allow for 10% incomplete interviews and missing data, around 700 cases as well as 700 controls will be needed. With this newly proposed sample size, we shall be able to achieve the 1st primary objective and address the interactions with major risk factors of the 2nd objective; however, power may be limited to cover the interactions with minor risk factors.
In addition, we will replace community controls by hospital controls because the cost of recruitment of community controls is much higher than the hospital controls. Another reason for not using community controls is the poor response rate, and our pilot study suggested a low response rate from the community controls (<40%). Using hospital controls with different diagnostic groups has been shown to have similar results to the community controls. We will recruit controls from the same hospitals of the cases with different diagnoses of disease. We will perform sensitivity analysis to test the robust results by excluding the diseases potentially related to night shift work from the controls.
Abstract as per original application
(English/Chinese):
Aim Breast cancer is the leading cause of cancer morbidity and mortality among women in Hong Kong, and the rate is accelerating. Although the upward trend is considered to be attributable to the ‘westernization’ of lifestyles, this probably contributes to only 41% of the breast cancer risk in the female population in combination with various genetic factors. A larger majority fraction of breast cancer etiology is environmental in origin, and this origin remains poorly understood. We aim to rectify this lack of knowledge through our intended project. Project Background In 2007, the International Agency for Research on Cancer (IARC) classified shift work that involved circadian disruption as probably being carcinogenic to humans (Group 2A); this, however, was on the basis of sufficient evidence from experimental animals but only on limited evidence from humans. Only two relevant epidemiological studies have been published since 2007, but they do not contribute much to addressing the limitations quoted by the IARC in 2007. None of the previous epidemiological studies has adequately captured the specific characteristics of nightshifts (e.g., the type, regularity, timing, frequency, and speed of rotating) in examining its association with breast cancer risk, and none has taken into account the potential confounding effects from environmental exposure to pesticides and other endocrine-disrupting chemicals (EDCs), known or suspected occupational carcinogens, the use of cosmetics containing estrogens in the breast area, etc. Brief Project Description We will study about 1,066 newly diagnosed female breast cancer cases and an equal number of age-matched controls randomly selected from the community. A standardized questionnaire will be used to collect information on each participant’s lifetime exposure to night shift work, environmental exposures to pesticides and other EDCs, occupational exposures, reproductive and anthropometric factors, smoking, diet, alcohol drinking, family cancer history, etc. With a more reliable exposure assessment and a more adequate control of the confounding factors, we will be able to ascertain whether exposure to night shift work is associated with an elevated risk of breast cancer among Hong Kong Chinese women and to thereby better understand the potential interactions with the major risk factors. Significance of Project Night shift work is prevalent in Hong Kong women. There will be far-reaching implications if a causal link between night shift work and breast cancer is confirmed by this proposed study, because even a slight decrease in the risk would result in a great reduction in public health burden.
Realisation of objectives: 1. We successfully recruited 767 eligible breast cancer incident cases with a response rate of 91.1%; the main reasons for the non-responses were no interest or poor medical condition. All eligible cases were consecutively identified from the Department of Surgery or Clinical Oncology of three hospitals in Hong Kong during the period 11/2011 to 05/2014, and were interviewed within three months after the diagnosis was made. Each eligible case was frequency matched in 5-year age groups by a control patient selected from the same hospital where the cases came from. We recruited 792 eligible controls with a broad disease pattern of diagnosis, with the response rate of 93%. To be eligible, the cases and controls must have no previously physician-diagnosed cancer at any site. 2. The relationship between night shift work and the risk of breast cancer had been investigated in our study. The exposure-response relationship of breast cancer risk with the exposure to short, moderate and long terms of night shift work were evaluated in our study. 3. We further explored the interactions which may exist between night shift work and several major risk factors, including menopausal status, light-at-night, sleep deprivation, diet, smoking, alcohol drinking, and family cancer history. Because the usage of the residential pesticides was quite rare and the occupational exposures to potential endorine disrupting chemicals (EDCs) were low in our study population, the current study does not have adequate power to examine the potential interactions between exposure to residential pesticides or EDCs and night shift work on the risk of breast cancer. 4. Evidence has shown that nightshift work may be associated with some digestive system diseases like gastritis and gastric/duodenal ulcer. Thus, sensitivity analysis was conducted to test the robust results by removing controls whose diagnosis are gastritis and gastric/duodenal ulcer.
Summary of objectives addressed:
Objectives Addressed Percentage achieved
1.To investigate the relationship between night shift work and the risk of breast cancer among Chinese women in Hong Kong; Yes100%
2.To explore the interactions which could exist between night shift work and several major risk factors, including menopausal status, light-at-night, sleep deprivation, residential pesticides, occupational exposures to potential EDCs, diet, smoking, alcohol drinking, and family cancer history. Yes100%
3.However, we have to reduce sample size from the originally proposed 1066 cases and 1066 controls to 700 subjects in each group due to limited budget obtained (our originally proposed budget has been cut down by 58.8%). We re-estimated sample size using a relatively conservative approach, 636 cases and an equal number of controls will be recruited in order to detect the risk of a modest size of 1.45 for exposures with prevalence rates about 18% to reach a reasonable power of 80% at the 5% significance level (one-sided). To allow for 10% incomplete interviews and missing data, around 700 cases as well as 700 controls will be needed. With this newly proposed sample size, we shall be able to achieve the 1st primary objective and address the interactions with major risk factors of the 2nd objective; however, power may be limited to cover the interactions with minor risk factors. Yes100%
4.In addition, we will replace community controls by hospital controls because the cost of recruitment of community controls is much higher than the hospital controls. Another reason for not using community controls is the poor response rate, and our pilot study suggested a low response rate from the community controls (<40%). Using hospital controls with different diagnostic groups has been shown to have similar results to the community controls. We will recruit controls from the same hospitals of the cases with different diagnoses of diseases. We will perform sensitivity analysis to test the robust results by excluding the diseases potentially related to night shift work from the controls.Yes100%
Research Outcome
Major findings and research outcome: Our study showed that there were 5.5% of breast cancer cases and 6.1% of controls who had ever worked at nightshift at least once per month for ≥1 year. There was no evidence for an association between ever nightshift work and breast cancer risk (OR=1.00, 95% CI: 0.58-1.71). Further analyses revealed that a possibly excess risk of breast cancer was restricted to women who had worked at nightshift for ≥15 years (adjusted OR=1.66, 95% CI: 0.70-3.90) but power is limited. Although this study tends to provide supportive evidence on a positive association between long-term nightshift work and breast cancer risk among Hong Kong Chinese women, this result would have to be confirmed by further larger studies. However, we failed to detect significant interactions between nightshift work and other major risk factors (e.g., menopausal status, smoking, alcohol drinking, and family cancer history) based on the current study scale with a relatively limited sample size. Nevertheless, this study showed some potential interesting associations when the analyses were further stratified by the menopausal status and family cancer history. For women having nightshift work ≥15 years, the relative risk of breast cancer in the post-menopausal women was much higher (OR=2.27, 95% CI: 0.73-7.04) than the pre-menopausal women (OR=0.95, 95% CI: 0.23-3.83), indicating a potential multiplicative interaction between menopausal status and nightshift work. Moreover, we found that the OR of breast cancer was higher in the long-term nightshift worker (≥15 years) who had a cancer history in the first-degree family members than those without a family history (OR=3.43, 95% CI: 0.66-17.92 vs. OR=1.11, 95% CI: 0.38-3.26); this indicates that a potential multiplicative interaction might exist between family cancer history and night shift work on the risk of breast cancer. Sensitivity analysis was conducted by excluding the controls with diagnoses of gastritis and gastric/duodenal ulcer, and the results remained unchanged, which suggests that the recruited controls are appropriate. In addition, two papers that are relevant to this GRF/RGC-funded project have been published in the peer-review journals (Annals of Oncology, 2013; Chinese Journal of Preventive Medicine, 2014). Another two relevant original manuscripts were submitted to the Journal of National Cancer Institute and European Journal of Cancer and now are under review (see Part C). Other relevant research outputs include three abstracts presented in the international conferences in Utrecht (06/2013) and Chicago (06/2014), and one invited speech to be presented in Guangzhou, China (11/2014) (see Part C).
Potential for further development of the research
and the proposed course of action:
As night shift work is the necessary component for many occupations, understanding of which specific pattern of shift work increase breast cancer risk, and how night shift work influences the pathway to breast cancer risk is prerequisite for the development of healthy workplace policy. The association between long-term nightshift work and breast cancer risk obtained from this GRF/RGC funded study among Hong Kong Chinese women needs to be confirmed by larger studies, while further research should also be done to look into the relation with specific characteristics of shift work and the duration of exposure. As the chronotype and sleep pattern may play a role in night shift work and the carcinogenesis, more studies on the gene variants especially melatonin related genes should be conducted; furthermore, the joint effects between genetic polymorphisms and long-term nightshift work on the risk of breast cancer warrant further studies, in particular the Asian population where the nightshift work is prevalent and incidence of breast cancer is increasing.
Layman's Summary of
Completion Report:
The shift work is prevalent in Hong Kong Chinese women, especially in the medical organization and service industry. Meanwhile, the breast cancer incidence in Hong Kong has been ranked as the second highest region in Asia, and the rate is increasing. This GRF/RGC funded project aimed to figure out whether exposure to nightshift work was associated with an elevated risk of breast cancer among Hong Kong Chinese women and to thereby better understand the potential interactions with the major risk factors. Results from this study demonstrated that a possibly excess risk of breast cancer was restricted to women who had worked at nightshift for ≥15 years (adjusted OR=1.66, 95% CI: 0.70-3.90), whilst there was no evidence for an association with the short-term nightshift work. We observed an enhanced risk of breast cancer (a possible multiplicative interaction) between the long-term nightshift work and post-menopausal status or women with a positive family cancer history on the risk of breast cancer, but there was no statistical significance due to limited power. Preventive lifestyles and the least damaging shiftwork schedules should be recommended to avoid the possible health consequences from the hazardous nightshift work.
Research Output
Peer-reviewed journal publication(s)
arising directly from this research project :
(* denotes the corresponding author)
Year of
Publication
Author(s) Title and Journal/Book Accessible from Institution Repository
2013 Wang F, Yeung KL, Chan WC, Kwok CC, Leung SL, Wu C, Chan EY, Yu IT, Yang XR, Tse LA*  A meta-analysis on dose-response relationship between night shift work and the risk of breast cancer. Annals of Oncology 2013 Nov;24(11):2724-32. doi: 10.1093/annonc/mdt283.  No 
2014 Tse Lap Ah*  Shift Work, Circadian Disruption and the Risk of Health [輪班工作、晝夜節律改變與健康效應]. Journal of Chinese Preventive Medicine. 2014 Sept;48(9)  No 
2015 Lap Ah Tse*, Li M, Chan WC, Kwok CH, Leung SL, Wu C, Yu IT, Yu WC, Lao X, Wang X, Wong CK, Lee PM, Wang F, Yang XR  Familial risks and estrogen receptor-positive breast cancer in Hong Kong Chinese women. PloS ONE. 2015 Mar 10;10(3):e0120741. doi: 10.1371/journal.pone.0120741.  No 
Feng Wang, Lap Ah Tse*, Wing-cheong Chan, Carol Chi-hei Kwok, Siu-lan Leung, Cherry Wu, Oscar Wai-kong Mang, Roger Kai-cheong Ngan, Mengjie Li, Foon-yiu Cheung, Wang-ming Seun, Miao Xiaoping, Xiaohong R. Yang, Ignatius Tak-sun Yu  Differential increase in invasive breast cancer incidence amongst birth cohorts 1896-1976 in Hong Kong women: Potential implications from emerging environmental risk factors (to be submitted to Journal of National Cancer Institute)  No 
Mengjie Li, Lap Ah Tse*, Wing-cheong Chan, Chi-hei Kwok, Siu-lan Leung, Cherry Wu, Ignatius Tak-sun Yu, Wai-cho Yu, Priscilla Ming-yi Lee, Chloe Hui-Tung Yu, Feng Wang, Xiaohong Rose Yang  Differential effects of tea consumption on pre- and post- menopausal breast cancer with distinct estrogen receptor in Hong Kong Chinese women (to be submitted to Breast Cancer Research and Treatment)  No 
Feng Wang, Lap Ah Tse*, Wing-cheong Chan, Carol Chi-hei Kwok, Siu-lan Leung, Cherry Wu, Oscar Wai-kong Mang, Roger Kai-cheong Ngan, Mengjie Li, Wai-cho Yu, Koon-ho Tsang, Sze-hong Law, Ying Zheng, Xiaoping Miao, Chunxiao Wu, Ignatius Tak-sun Yu, Fan Wu, and Xiaohong R. Yang  Disparities of time trends and birth cohort effects on invasive breast cancer incidence in Shanghai and Hong Kong pre- and post-menopausal women (to be submitted to International Journal of Cancer)  No 
Recognized international conference(s)
in which paper(s) related to this research
project was/were delivered :
Month/Year/City Title Conference Name
June/2013/Utrecht, The Netherlands Preliminary results of a case-control study of night shift work and breast cancer among Hong Kong women  EPICOH 2.0.13 (The 23rd International Conference on Epidemiology in Occupational Health, Utrecht, The Netherlands, 18 - 21 June 2013.) 
June/2013/Utrecht, The Netherlands Night-shift work and risk of breast cancer: a meta-analysis  EPICOH 2.0.13 (The 23rd International Conference on Epidemiology in Occupational Health, Utrecht, The Netherlands, 18 - 21 June 2013.) 
June/2014/Chicago, USA Long-term nightshift work and breast cancer risk in Hong Kong women: results update  The 24th International Conference on Epidemiology in Occupational Health (EPICOH 2014), 24 June - 27 June 2014 Chicago, United States of America 
November/2014/Guangzhou, China Night shift work and risk of breast cancer in Hong Kong women  International Symposium on Work Injury Prevention and Rehabilitation 2014 (invited speech; RGC funding will be acknowledged in the presentation; the invitation letter is attached) 
Other impact
(e.g. award of patents or prizes,
collaboration with other research institutions,
technology transfer, etc.):
This GRF/RGC funded project led us to having international research collaboration with the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (USA) for breast cancer study, 2013-2014. [Tse LA (HK lead PI), Wang F, Yu ITS Chan WC, Wu C. Characterization of molecular subtypes of breast cancer and their relationships with known breast cancer risk factors among Chinese women in Hong Kong – a pilot study, 2013. National Institutes of Health, National Cancer Institute, USA. Funded amount: US$ 95,600] We are exploring further collaborations with the NCI/NIH (USA) for the next three years.

  SCREEN ID: SCRRM00542