A Systematic Review and Meta-Analysis on Night Shift Work and Breast Cancer Risk for Female Employees Public

Abstract

Background: In 2007, the International Agency for Research on Cancer (IARC) came to the conclusion based on "limited evidence for humans on the carcinogenicity of shift work that involves night shift work" that "shift work [that] involves circadian disruption is probably carcinogenic to humans." Breast cancer is one of the most common forms of cancer for women in Western societies where up to 15 to 20% of the total workforce is involved in night shift work. Consequently, female employees that have night shift work may have an increased risk of breast cancer.

Objectives: This study reviewed case-control and cohort studies on night shift work and breast cancer risk. It will assess if current research is conclusive on the association between night shift work and increased breast cancer risk amongst female night shift workers.

Methods: A systematic review and meta-analysis was performed on previous research studies measuring the association between night shift work and breast cancer risk. Study characteristics were extracted independently from each study. Weighted mean effect sizes, using both fixed- and random effects models, were calculated; greater effect sizes indicated an increased risk of breast cancer associated with night shift work. Heterogeneity between studies was also evaluated.

Results: Fixed- and random effects models found a significantly elevated breast cancer risk among female night shift workers in case-control studies and only a slightly elevated breast cancer risk in cohort studies. Case-control studies were found to be moderately homogeneous whereas cohort studies showed significant heterogeneity. The difference in aggregated breast cancer risk and heterogeneity between the two types of studies may be a consequence of the varying definitions for night shift work exposure and the differences in sample population.

Conclusions: Although, this study suggests that night shift work may increase the risk of breast cancer, the association between night shift work and breast cancer risk is still inconclusive due to the limited evidence. The possible increase in the risk of breast cancer observed in the meta-analysis is not robust enough due to some heterogeneity observed in the case-control studies and the great variability and heterogeneity observed in the cohort studies.

Table of Contents

1. INTRODUCTION:..... 1

1.1. Background..... 1

1.2. Significance..... 7

1.3. Research Objective..... 9

1.4. Aim and Hypothesis..... 9

2. METHODS:..... 10

2.1. PRISMA Statement..... 10

2.2. Searching strategy..... 10

2.3. Eligible studies..... 11

2.4. Ineligible studies..... 12

2.5. Definitions..... 12

2.6. Effect measures..... 13

2.7. Statistical analysis..... 13

2.7.1. Calculating effect sizes..... 13

2.7.2. Testing for heterogeneity..... 16

2.7.3. Determining outliers..... 18

2.8. Evaluation for heterogeneity and publication bias..... 19

3. RESULTS:..... 19

3.1. Studies identified..... 19

3.2. Study characteristics..... 20

3.3. Assessing the quality of studies..... 24

3.3.1. Comparison groups..... 24

3.3.2. Quality assessment of studies..... 25

3.3.3. Night shift work definitions..... 28

3.4. Meta-analysis..... 30

3.5. Evaluation for publication bias..... 34

4. DISCUSSION:..... 35

4.1. Summary of key findings..... 35

4.2. Previous research..... 39

4.3. Comparison with previous reviews..... 40

4.4. Potential significance of findings..... 42

4.5. Limitations..... 43

5. CONCLUSIONS:..... 43 REFERENCES:..... 45 APPENDICES:..... 48

Appendix A - Newcastle-Ottawa Quality Assessment Scales for case-control and cohort studies ..... 48

Appendix B - Equations..... 52 TABLES, FIGURES, and EQUATIONS

Table 1 - Search terms used on electronic databases (PubMed and Web of Science)..... 11

Table 2 - Study Characteristics of case-control studies..... 22

Table 3 - Study characteristics of cohort studies..... 23

Table 4 - Quality assessment of case-control studies..... 26

Table 5 - Quality assessment of cohort studies..... 27

Table 6 - Fixed effects model for case-control studies..... 30

Table 7 - Fixed effects model for cohort studies..... 30

Table 8 - Heterogeneity for case-control studies..... 31

Table 9 - Heterogeneity for cohort studies..... 31

Table 10 - Random effects model for case-control studies..... 32

Table 11 - Random effects model for cohort studies..... 32

Table 12 - Standardized residuals and Z scores for case-control and cohort studies..... 33

Figure 1 - Mechanisms by which chronic exposure to a 60 Hz electric field leads to an increased DMBA-induced mammary carcinogenesis in rats..... 3

Figure 2 - Flow diagram: night shift work and breast cancer risk..... 20

Figure 3 - Forest plot: fixed effects model for case-control studies..... 30

Figure 4 - Forest plot: fixed effects model for cohort studies..... 31

Figure 5 - Forest plot: random effects model for case-control studies..... 32

Figure 6 - Forest plot: random effects model for cohort studies..... 33

Figure 7 - Funnel plot: case-control studies..... 34

Figure 8 - Funnel plot: cohort studies..... 35

Equation 1 - Calculating the variance of LnOR..... 14

Equation 2 - Calculating the variance of LnRR..... 14

Equation 3 - Calculating the weight..... 15

Equation 4 - Calculating the relative weight..... 15

Equation 5 - Calculating the standard error of LnOR..... 15

Equation 6 - Calculating the standard error of LnRR..... 15

Equation 7 - Calculating the 95% confidence interval..... 15

Equation 8 - Calculating the effect size..... 16

Equation 9 - Calculating the combined effect measurement..... 16

Equation 10 - Calculating the combined effect variance..... 16

Equation 11 - Calculating the Q statistic..... 17

Equation 12 - Calculating the T² statistic..... 17

Equation 13 - Calculating the I² index..... 17

Equation 14 - Calculating H..... 18

Equation 15 - Calculating the standardized residual..... 18

Equation 16 - Calculating the Z score..... 18

About this Master's Thesis

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School	Rollins School of Public Health
Department	Environmental Health
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Occupational Health and Safety
Mot-clé	circadian rhythm disruption breast cancer melatonin night shift work night shift work schedule tolerance carcinoma rotating night shift breast cancer incidence breast cancer risk
Committee Chair / Thesis Advisor	Liu, Yang, Emory University
Committee Members	Feng, Wang, Chinese University of Hong Kong Tse, Shelley, Chinese University of Hong Kong
Partnering Agencies	Emory University schools, faculty or affiliated programs University, college or educational institution (other than Emory)

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