A meta-analysis of international data confirms a positive association between long-term night shift work and an increased overall risk for cancer in women, particularly breast cancer.

In North America and Europe, working the night shift was associated with a 32% increased risk for breast cancer overall (odds ratio [OR], 1.316), the authors report.

But the risk was even higher in one specific group: Night nurses were found to have a "remarkable" 58% increased risk (OR, 1.577) for breast cancer.

Breast cancer risk was also elevated in a dose-response way, consistent with earlier studies. For every 5 years a women spent working nights, breast cancer risk increased by 3.3% (OR, 1.033), the study authors say.

The review, published online January 8 in Cancer Epidemiology, Biomarkers & Prevention, was led by Xuelei Ma, PhD, from the West China Medical Center of Sichuan University, Chengdu.

"By systematically integrating a multitude of previous data, we found that night shift work was positively associated with several common cancers in women," said Dr Ma in a statement. "Given the expanding prevalence of shift work worldwide and the heavy public burden of cancers, we initiated this study to draw public attention to this issue so that more large cohort studies will be conducted to confirm these associations."

More research is needed to understand the mechanisms behind this association and to better protect women working night shifts against increased cancer risk, Dr Ma told Medscape Medical News.

"Breast cancer is the most diagnosed cancer among women worldwide, with higher incidence in developed regions," he said. "These results might help establish and implement effective measures to protect female night shifters. Long-term night shift workers should have regular physical examinations and cancer screenings."

Long-term night shift workers should have regular physical examinations and cancer screenings. Dr Xuelei Ma

Demands of the Modern World

The productivity demands of the modern world call for increasing numbers of employees in the food production, entertainment, healthcare, and transportation industries to work across time zones, the investigators note.

Large numbers of people are being exposed to night shift work, which brings [a] huge detrimental impact on health. Ma et al

The third European Union survey showed that as early as 2000, 76% of employees regularly worked beyond normal working hours, the study authors point out. Up to 21.9% of men and 10.7% of women said they were exposed to shift work, and 7% permanently worked a night shift.

A 2004 European survey revealed that regularly working overtime was the most common form of "flexible" working hours and that this was linked to negative effects on stress, sleep, and social and mental health.

In 2012, a ground-breaking Danish study of female military workers reported by Medscape Medical News showed that the risks to health of working night shifts were greater in women who considered themselves "morning persons" than in women who considered themselves "night owls."

Details of the Meta-analysis

The meta-analysis conducted by Dr Ma and colleagues looked at the association between long-term night shift work and the risk for 11 types of cancer using data from 26 cohort studies, 24 case-control studies, and 11 nested case-control studies. The 61 studies, updated to October 2016, included nearly 4 million women with cancers of the breast, lung, skin, and digestive and reproductive systems.

The overall risk for cancer increased by 19% among women working night shifts, compared with those who did not, in North America, Europe, Australia, and Asia. In addition to the increased risk for breast cancer already noted above, the risk for skin cancer also increased by 41% and risk for gastrointestinal cancer by 18% in women who worked night shifts.

Significant heterogeneity was observed in the groups of breast cancer (I2 = 80.4%; P = .000), skin cancer (I2 = 64.7%; P = .009), and uterine cancer (I2 = 59.6%; P = .042). There was no evidence of heterogeneity in the other cancer groups.

The association between working the night shift and increased breast cancer risk in women was seen only in those living in North America and Europe, a finding that Dr Ma said surprised the investigators. "It is possible that women in these locations have higher sex hormone levels, which have been positively associated with hormone-related cancers such as breast cancer," he suggested.

"The positive relationship between endogenous hormone levels and risk of breast cancer supports therapeutic strategies that target estrogen signaling," Dr Ma added, noting that in women with estrogen receptor–positive breast cancer, the clinical benefits of adjuvant endocrine therapy "are well established."

Nurses Appear Most Vulnerable

Of all the professions occupied by women, nursing appeared to be the most vulnerable to the carcinogenic effects of regular night shift work. A secondary analysis carried out by Dr Ma and colleagues looked at long-term night shift work in female nurses and the risk for six types of cancer. It showed that night nursing was also associated with a 35% increased risk for gastrointestinal cancer (OR, 1.350) and a 28% increased risk for lung cancer (OR, 1.280).

A nonsignificant effect was observed for ovarian cancer (OR, 1.135), and no effect was seen for cervical cancer (OR, 0.980), the investigators report.

"Nurses who worked the night shift were of a medical background and may have been more likely to undergo screening examinations," Dr Ma noted. "Another possible explanation for the increased cancer risk in this population may relate to the job requirements of night shift nursing, such as more intensive shifts."

Working at night leads to disruption in circadian rhythm and suppression of nocturnal melatonin secretion, the study authors note. Over the short term, this results in what's commonly referred to as "jet lag." Symptoms include sleep disorders, digestive troubles, fatigue, emotional fluctuation, and reduced physical activity.

Over the long term, however, research shows that circadian rhythm disruption and nocturnal melatonin suppression function as carcinogens that increase tumor incidence. Prolonged circadian disturbance has also been associated with increased risk for cardiovascular disease, as well as neuropsychiatric and endocrine system disorders.

An impact on urinary melatonin could play a role in sex hormone increases thought to be associated with hormone-dependent cancers, they note. Although night shift work was strongly associated with higher risk for breast cancer in women, this review found no such effect for other cancers in women that are hormone dependent, such as ovarian and uterine cancer, the researchers say.

Lifestyle changes, such as irregular eating hours, reduced physical activity, and work-related stress, may also contribute to this increased cancer risk, Dr Ma told Medscape Medical News.

When asked whether smoking could be a contributing factor, he noted that previous studies adjusted for smoking "reported that ever-smokers counted a larger percentage among cases compared to noncases."

However, the current analysis was limited by a "lack of consistency regarding confounding factors," Dr Ma pointed out. In addition, "no stratified analysis was performed on smoking, thus no clear association was identified between smoking and cancer risk among night shift nurses."

Other study limitations include the lack of a consistent definition for night shift work across studies, as well substantial between-study heterogeneity that could weaken the association between working at night and cancer risk, Dr Ma and colleagues say.

The study authors have disclosed no relevant financial relationships.

Cancer Epidemiol Biomarkers Prev. Published online January 8, 2018. Abstract

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