Night-shift Work and Breast Cancer

NCT ID: NCT06786949

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 6000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-01-31
• Study Completion Date: 2025-12-31

Brief Summary

Scientific evidence established about the effects of night work on health both in the short term (insomnia, excessive sleepiness, difficulty concentrating or lack of energy) and in the long term (moderately high risk of developing cardiovascular disease, type 2 diabetes, depression, cancer). In light of the scientific evidence, the IARC (International Agency for Research on Cancer) has listed night work as a probable human carcinogen (Group 2). With respect to current knowledge, the present study could provide valuable help in understanding the mechanisms by which circadian rhythm alteration acts at the genetic level in terms of promoting oncogenesis. Furthermore, by studying its association with other risk factors, understand whether there is a pattern of women more susceptible to its oncopromoting action.

Detailed Description

Certain bodily functions, such as wakefulness and sleep, regulation of blood pressure and body temperature, the immune system, gene expression, and secretion of hormones--think of cortisol, for example--follow variations that are stably repeated every 24 to 25 hours. The biological clock that marks this cyclical rhythm is represented by neurons in the suprachiasmatic nucleus of the hypothalamus. Of the circadian system, three components should be considered: (a) the input pathways that transmit signals to synchronize the endogenous central clock with the external environment, (b) the central clock generates rhythms, and (c) the output pathways that transmit the signal from the central clock to other regulatory systems in the brain and body. The most powerful regulator of the input pathways is light, which-as is well known-is captured by the five retinal photoreceptors, including the intrinsically photosensitive retinal ganglion cells [ipRGCs], which, through the production of melanopsin, transmit the signal to the central circadian clock. Such physiological mechanisms, which have remained unperturbed for thousands of years, have been disrupted by the spread of artificial lighting, which, inevitably, alters the natural synchronization of the internal clock with sunlight.

The effects that this misalignment produces are clearly visible in night workers who frequently have to expose themselves to light at "atypical" hours. In this sense, in fact, according to current legislation (see Art. 1, Legislative Decree No. 66 of April 8, 2003, implementing Directives 93/104/EC and 2000/34/EC, concerning certain aspects of the organization of working time), a night worker is defined as anyone who works for a period of at least seven consecutive hours including the interval between midnight and 5 a.m. It follows with palpable evidence that there is an increased risk that, under night work conditions, the alteration of the sleep-wake rhythm may take on a chronic character. In this regard, scientific evidence about the effects of night work on short-term health is well established: such as insomnia, excessive sleepiness, difficulty in concentration or lack of energy. While there is also scientific evidence that some repercussions may also occur in the long term. This is, in that case, the moderately high risk of developing cardiovascular disease, type 2 diabetes, depression, and, not least, cancer. Indeed, in 2007, in light of scientific evidence, the IARC (International Agency for Research on Cancer) listed night work as a probable human carcinogen (Group 2). Breast cancer generally represents the second most frequent neoplastic disease in women. The incidence of new cases worldwide in 2017 was estimated to be 1.9 million, higher in industrialized countries. From a pathogenetic point of view, the association between night shift work and breast cancer is highly plausible.

Conditions

Breast Cancer Risk Factors

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Subgroup 1

For the analysis of possible risk factors for breast cancer (secondary objective 1), a nested case-control study will be conducted on a subpopulation of the health worker cohort: 100 cases will be selected from the health workers in the cohort who have been diagnosed with breast cancer; 3 healthy controls will be selected for each case (300 total) and will be matched to the cases based on center, age, and period of first employment

Questionnaire

Intervention Type: OTHER

All cases and controls will be contacted by telephone or e-mail and invited to participate in the study. Female workers who decide to join the study will be asked to go to their company's occupational health clinic where they will undergo administration of a questionnaire to investigate possible known and unknown risk factors for breast cancer

Subgroup 2

For the measurement of biomarkers of aging whose expression might be associated with night shifts (secondary objective 2), 200 health care workers who have been exposed to at least 6 night shifts per month in the past 6 months and 200 unexposed health care workers, plus 50 other health care workers in each group to prevent possible nonadherence to the study, will be randomly selected from the cohort of health care workers currently still in service.

Blood samples for biomarker measurement

Intervention Type: DIAGNOSTIC_TEST

Women who give consent to undergo this phase of the study will be called back to the center and will be asked to provide a blood sample

Interventions

Questionnaire

All cases and controls will be contacted by telephone or e-mail and invited to participate in the study. Female workers who decide to join the study will be asked to go to their company's occupational health clinic where they will undergo administration of a questionnaire to investigate possible known and unknown risk factors for breast cancer

Intervention Type: OTHER

Blood samples for biomarker measurement

Women who give consent to undergo this phase of the study will be called back to the center and will be asked to provide a blood sample

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Health workers with any type of contract and qualification (doctors, nurses, OSS) in service at IRCSS AOUBO and AOU "G. Martino" of Messina for at least six months between 1.1.2000 and 31.12.2021
• Age between 20 and 70 years at the start of study follow-up (6 months after recruitment or 1.1.2000)
• Female gender
• For secondary objective 2 of the study only, women exposed to night work must have worked at least 6 night shifts per month in the past six months

Exclusion Criteria

• Women found to be positive for BRCA1 and BRCA2 genetic mutation (BRCA1 and 2 mutations are searched for by geneticists in sick women for whom there is a consistent suspicion of mutation)
• Women with prior history of breast cancer at the time of recruitment or within six months thereafter.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

IRCCS Azienda Ospedaliero-Universitaria di Bologna

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesco Violante, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Locations

IRCCS Azienda Ospedaliero - Universitaria di Bologna, U.O. Medicina del Lavoro

Bologna, , Italy

Site Status: RECRUITING

AOU G. Martino Messina U.O.S.D. Medicina del Lavoro

Messina, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Francesco Violante Violante, MD

Role: CONTACT

francesco.violante@asop.bo.it

051 2142611

Facility Contacts

Francesco Violante, MD

Role: primary

francesco.violante@asop.bo.it

051 2142611

Concettina Fenga, MD

Role: primary

concettina.fenga@unime.it

090 2211

Other Identifiers

PNRR-MAD-2022-12376823

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

BC-NSW-02/2023

Identifier Type: -

Identifier Source: org_study_id