Night Shift Ups Breast Cancer Risk: New Data

Zosia Chustecka

May 29, 2012

May 29, 2012 — Another study has shown an association between night-shift work and breast cancer. It was conducted in Danish female military workers; many of the previous studies focused on nurses or other people who do shift work, such as flight attendants.

It showed, for the first time, that women who prefer mornings (so-called "larks") are at greater risk when they work night shifts than women who prefer evenings (so-called "owls").

The results, from an analysis of data on more than 18,551 women, are published online May 28 in Occupational and Environmental Medicine.

"This study supports to the hypothesis that night-shift work increases the risk for breast cancer," say researchers Johnni Hansen, PhD, and Christina Lassen, from the Institute of Cancer Epidemiology, Danish Cancer Society in Copenhagen.

"So far, 10 of 13 epidemiologic studies of night-shift work have shown an increased risk for breast cancer, and about 50 animal studies have shown the same tendency," Dr. Hansen told Medscape Medical News.

It is...too early to state that night-shift work increases the risk for breast cancer, but the evidence is growing.

"It is, however, too early to state that night-shift work increases the risk for breast cancer, but the evidence is growing," he said. There is very little epidemiologic evidence on other types of cancer so far, he added.

The International Agency for Research on Cancer concluded in 2007 that shift work that involves circadian disruption is "probably carcinogenic" to humans. In 2009, Denmark became the first country to pay government compensation to women who developed breast cancer after long spells of working at night.

Study From "Top Notch" Researcher

The current study, from a "top notch" researcher in the field, "comes in a series of mostly supportive studies, none of which can prove cause and effect but together are getting close," said Richard Stevens, PhD, professor of cancer epidemiologist at the University of Connecticut Health Center in Farmington

Dr. Stevens was not involved in the study, but has published on circadian rhythm disruption, specifically on "light at night" increasing the risk for breast cancer.

He explained that this Danish study has 2 features that are new: diurnal preference data and information on sun exposure.

The researchers highlight the diurnal preference data as being a "unique aspect" of their study. In a detailed questionnaire, they asked women whether they had a preference for morning or evening, identifying the women as being either larks or owls.

Other questions covered the major potential confounders of breast cancer, including body mass index, alcohol consumption, menopausal status, use of hormone replacement therapy, use of contraceptives, occupational exposure to radar or electromagnetic fields, age at menarche and menopause, number of childbirths, tobacco use, occasional sun exposure, occupational physical activity, and workload.

Taking these confounders into account "changes the results only marginally," they note.

Overall Doubling of Risk

For their study, the researchers scoured data on 18,551 women who had served in the Danish Army from 1964 to 1999, and identified 218 women who developed breast cancer. They were able to contact 210 of these women, and matched them with 899 control subjects for further study.

In total, 141 women with breast cancer and 551 control subjects completed the questionnaire.

After adjustment for confounders, the analysis showed that women who worked night shifts at least 3 times a week for at least 6 years were more than twice as likely to have breast cancer as matched control subjects (odds ratio [OR], 2.3).

Working fewer than 2 nights per week did not appear to increase the risk for breast cancer, presumably because there was less disruption of the body clock, the researchers note.

Striking Difference Between Larks and Owls

Among the women who worked more than 3 nights per week for at least 6 years, there was a striking difference between those with a preference for mornings and those with a preference for evenings. The self-identified larks who worked nights had a nearly 4-fold increase in risk for breast cancer, compared with matched control subjects who did not work nights (OR, 3.9); the owls who worked nights had a 2-fold increase in risk for breast cancer, compared with control subjects.

However, among women who did not work night shifts, larks tended to have a lower overall risk for breast cancer than owls.

This suggests that larks are less tolerant of night-shift work than owls, and that this observation warrants exploration in larger studies, the researchers note.

Dr. Hansen told Medscape Medical News that they asked specifically about diurnal preferences because of evidence that it is associated with a differential expression of clock genes.

These clock genes are involved in the regulation of 10% to 20% of the entire genome, and are related to breast cancer risk, he explained. Previous work has suggested that larks are more genetically susceptible to changes in circadian rhythm (consistent with a genetic variant of the PER3 long repeat) that have been associated with an increase in breast cancer risk.

"Our observation is consistent with this," Dr. Hansen noted.

Dr. Stevens highlighted this result, saying that it is consistent with the prediction that morning types who do shift work are at greatest risk.

He also highlighted the information on sun exposure. One of the theories put forward to explain this increased risk for breast cancer is that night-shift workers are less exposed to ultraviolet radiation from the sun (the most important source of vitamin D production), Dr. Hansen said. However, the questionnaire used in this Danish study showed that women who worked at night reported more exposure to sunlight than the women who worked during the day, because they are inside during normal week days, he said.

How Is Cancer Risk Increased?

Several other hypotheses, some partly overlapping, have been put forward to explain how night-shift work increases the risk for breast cancer.

Many focus on the exposure to light at night, which decreases the night hormone melatonin that seems to protect against cancer, Dr. Hansen explained. This can also cause circadian disruption, where "the master clock in the brain become desynchronized from local cellular clocks in different organs, including the breast."

"Repeated phase shifting with internal desynchronization may lead to defects in the regulation of the circadian cell cycle, favoring uncontrolled growth," he said.

In addition, sleep deprivation after night-shift work leads to suppression of immune surveillance, which might permit the establishment and/or growth of malignant clones," he continued.

"Finally, long-term exposure to light at night may result in epigenetic changes," he said.

Melatonin Has AntiCancer Activity

"This is an excellent paper," said David Blask, MD, PhD, head of chrono-neuroendocrine oncology at Tulane University School of Medicine in New Orleans, Louisiana. It replicates most of the other studies done in this field, and again shows an increased risk for breast cancer related to night shifts.

"I think the evidence is getting stronger that night-shift work is a risk factor for breast cancer, especially with this new study, which is the eleventh to show such an effect," he said. "In science, we draw conclusions on the preponderance of evidence. The total picture is getting stronger and is backed up with the laboratory work that we and others have done," he told Medscape Medical News.

Dr. Blask's team previously showed that melatonin has direct anticancer activity on breast cancer cells, which they proposed as a mechanistic explanation for why shift workers are at increased risk. In a study published several years ago (Cancer Res. 2005;65:11174-11184), his team found that blood samples taken from women at night had high levels of melatonin, which had an marked inhibitory effect on breast cancer cells growing in vitro, whereas blood samples taken from the same women during daylight had much lower levels of melatonin and allowed the tumor cells to proliferate. "These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night-shift workers," the researchers concluded.

The study was supported by a grant from the Danish Ministry of Defence. The authors have disclosed no relevant financial relationships.

Occup Environ Med. Published online May 28, 2012. Abstract

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