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\begin{document}

\title{Cancer Patients Circadian Rhythm Assessment Based on
Morningness-Eveningness Preference}



\author[1]{Ghazal Daftari}%
\author[1]{Nasim Khajavirad}%
\author[1]{Mahsa Abbaszadeh}%
\author[1]{Sahar Karimpour Reyhan}%
\affil[1]{Tehran University of Medical Sciences}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: The circadian rhythm regulates various physiological
processes, including sleep-wake cycle, cell division and cancer
development. Aims: This study aimed to investigate circadian rhythm
patterns in cancer patients. Methods and results: In this
cross-sectional study, 150 cancer patients admitted to the internal ward
of Tehran's Imam Khomeini Hospital Complex in the fall of 2022 were
evaluated. The demographic characteristics of patients were collected
using a checklist. Patients also completed a morningness-eveningness
questionnaire (MEQ). Utilizing Analysis of Variance (ANOVA) and Fisher's
exact test, circadian rhythm types with continuous and categorical
variables were compared. The mean age of the study's participants was
49.83 \selectlanguage{ngerman}± 14.53 years. A total of 82.7\% (n=124) had non-hematological
cancers, and breast cancer was the most prevalent type of cancer among
patients (23.3\%). The MEQ of the patients studied ranged from 41 to 74,
with a mean score of 56.6 ± 6.34. Conclusion: According to the findings
of this study, the circadian rhythm is distributed normally among the
participants.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Cancer Patients Circadian Rhythm Assessment Based on
Morningness-Eveningness Preference}

Ghazal Daftari\selectlanguage{ngerman}ª, Nasim khajavirad\selectlanguage{english}?\textsuperscript{*}, Mahsa
Abbaszadeh?, \selectlanguage{english}Sahar Karimpour Reyhan?

\selectlanguage{ngerman}ªSchool of Medicine, Tehran University of Medical Science, Tehran, Iran.

\selectlanguage{english}?Department of Internal Medicine, Imam Khomeini Hospital Complex, Tehran
University of Medical Science, Tehran, Iran.

*Corresponding author:

Nasim khajavirad

Address: Department of Internal Medicine, Imam Khomeini Hospital
Complex, Keshavarz Boulevard, Tehran, Iran, Postal Code:1419733141

Email: Ghazall.daftari@gmail.com

\textbf{Abstract}

Background: The circadian rhythm regulates various physiological
processes, including sleep-wake cycle, cell division and cancer
development.

Aims: This study aimed to investigate circadian rhythm patterns in
cancer patients.

Methods and results: In this cross-sectional study, 150 cancer patients
admitted to the internal ward of Tehran's Imam Khomeini Hospital Complex
in the fall of 2022 were evaluated. The demographic characteristics of
patients were collected using a checklist. Patients also completed a
morningness-eveningness questionnaire (MEQ). Utilizing Analysis of
Variance (ANOVA) and Fisher's exact test, circadian rhythm types with
continuous and categorical variables were compared. The mean~age of the
study's participants was 49.83 \selectlanguage{ngerman}± 14.53 years. A total of~82.7\% (n=124)
had non-hematological cancers, and breast cancer was the most prevalent
type of cancer among patients (23.3\%). The MEQ of the patients studied
ranged from 41 to 74, with a mean score of 56.6 ± 6.34.

Conclusion: According to the findings of this study, the circadian
rhythm is distributed normally among the participants.

\emph{\textbf{Keywords}:} Cancer, Circadian Rhythm, MEQ, Chronotype,
clock genes

\textbf{Introduction}

The circadian clock with a 24-hour period is an essential biological and
behavioral system that persists in plants, animals, and humans and
regulates a variety of processes, including the cell cycle, body
temperature, immunity, heartbeat, basal metabolism, blood pressure,
hormone secretion, sleep-wake cycle, feeding, and glucose homeostasis
(1). The system is coordinated with environmental stimuli such as food
intake, light, and temperature (2). In humans, the circadian rhythm
consists of two components: the brain clock in the anterior
hypothalamus, supra chiasmatic nucleus (SCN), and the peripheral clock
in the individual cells (3, 4, 5, 6). The brain clock regulates the
peripheral clock of cells and functions as a pacemaker (3, 4, 5, 6).
Cellular clocks have autonomous rhythms and answer to intermittent
signals from the SCN (3, 4, 5, 6). Additionally, circadian pathway genes
control the circadian rhythm (7, 8).

In 1917, 1978, 1997, and 2001, the clock genes were reported for the
first time in the fruit fly \emph{Drosophila} , the
fungus\emph{Neurospora} , the rat, and finally the human, respectively
(9)\emph{.} In 2017, the Nobel prize was awarded to scientists who
discovered critical molecular mechanisms that control the circadian
rhythm (10, 11). The \emph{Per} (period homolog)1, 2, 3, \emph{Clock}
,\emph{BMall} , and \emph{Cry} (cryptochrome) 1,2 genes and their
products constitute a transcription-translation feedback loop (TTFL)
associated with the circadian rhythm (12). During the day, \emph{Clock}
and \emph{BMall} interact to initiate the transcription of the
\emph{Cry} and \emph{Per} genes (12). The\emph{Cry} and \emph{Per}
proteins are subsequently linked in the cytoplasm (12). This complex
migrates to the nucleus and inhibits\emph{BMall} and \emph{Cry}
gene-mediated transcription (12). The\emph{Cry-Per} complex is destroyed
at night, and the cycle begins again (12).

Cancer is a significant cause of death worldwide (13). Cancer incidence
has increased due to aging, changes in associated risk factors, and
socioeconomic developments (14). Furthermore, some mutations in DNA
replication and exogenous or endogenous DNA damage are associated with
cancer (15, 16). Several studies showed that disruption in circadian
rhythm results in metabolic syndrome, endocrine disorders, and cancer
(17). In circadian patterns, individuals are typically classified as
morning or evening types (18). Morning types wake up early and function
better in the morning (18). Evening types stay up late and perform best
at night (18). Dysregulation of circadian rhythms in humans is
associated with different cancers such as hepatocellular carcinoma (19),
colon (20), ovarian cancers (21), prostate (22), and lung (23).
Consequently, the proper function of clock proteins and circadian rhythm
plays a crucial role in cancer prevention and treatment (24). In this
study, we aimed to assess the circadian rhythm types using MEQ in cancer
patients\emph{.}

\textbf{Materials and Methods}

2.1. Study participants

This cross-sectional study was conducted on 150 patients with
hematologic and non-hematologic cancers, ages 16 to 80, admitted to the
internal ward of Tehran's Imam Khomeini Hospital Complex in the fall of
2022. Initial estimates placed the sample size at 145 patients, based on
a study indicating that circadian rhythm disturbances and sleep
disorders were prevalent in 30-75\% of cancer patients, or nearly twice
the rate in the general population (25). Five additional patients were
added for a total of 150 to prevent losses. Inclusion criteria were age
15 or older, a cancer diagnosis, consent to participate in the study,
absence of comorbidities, and absence of intubation. Exclusion criteria
were using Melatonin, sedative, and hypnotic medications, significant
cognitive impairment, night-shift workers, and end-stage patients. This
study was conducted per the Declaration of Helsinki and was approved by
the Imam Khomeini Hospital Complex, Tehran University of Medical
Science, Tehran, Iran, Ethics Committee (ethics number:
IR.TUMS.IKHC.1398.28). All patients were informed of the study, and
consent forms were obtained.

2.2. Clinical and demographic evaluation

Researchers designed a questionnaire to collect demographic and clinical
information, including gender, age, weight, height, marital status,
education, occupation, type of cancer, duration of illness, number of
hospitalizations, and history of chemotherapy or/and radiotherapy or/and
surgery. The questionnaire's content was evaluated by specialists and
deemed suitable for use.

2.3. The morningness-eveningness questionnaire

The circadian type of participants was evaluated using MEQ, which was
initially presented by Östberg and Horne (26). MEQ is a self-assessment
questionnaire comprising 19 questions; the scores range from 16 to 86.
The score weighting of the questions is not equal. This questionnaire
describes five behavioral types: definitely morning type (70-86 scores),
moderately morning type (59-69 scores), neither type (42-58 scores),
moderately evening type (31-41 scores), and definitely evening type
(31-41 scores) (27). The Persian form of MEQ's validity and reliability
have been established (\selectlanguage{greek}α \selectlanguage{english}= 0.79) (28).

2.4. Statistical analysis

Statistical Package Software for Social Science (SPSS) version~18~was
used to analyze the data, and P \textless{} 0.05 was considered
statistically significant. Continuous variables were assessed using the
mean and standard deviation, while categorical variables were evaluated
using frequency and percentage. The Analysis of Variance (ANOVA) test
was used to examine the relationship between means of age, time of
cancer diagnosis, hospital admissions, chemotherapy and radiotherapy
sessions, and circadian rhythm types. Furthermore, Fisher's exact test
was used to determine the relationship between chronotype and gender,
educational level, marital status, patient condition, treatment methods,
occupation, and type of cancer. Kolmogorov-Smirnov analysis was used to
verify the normality of the variable distribution.

\textbf{Results}

The age and body mass index (BMI) of 150 patients in this study ranged
from 16 to 80 y (49.83 \selectlanguage{ngerman}± 14.53) and 12.41 to 41.79
kg/m\textsuperscript{2} (25.09 ± 5.32), respectively. Tables 1 and 2
show the participants' demographic, clinical, and medical
characteristics.

Table 1 near here.

Among the participants, 17.3\% (n=26) had hematologic cancers. Cancer
incidence ranged from 1 to 180 months (23.26 ± 29.3). The frequency of
chemotherapy and radiotherapy sessions varied from 1 to 13 (3.61 ±
2.37), 0 to 70 (8.24 ± 9.79), and 0 to 50 (5.50 ± 11.5) times,
respectively, for patients admitted to the hospital due to cancer.

Table 2 near here.

\par\null

Total MEQ scores ranged between 41 and 74 (56.6 ± 6.34). In this study,
2\% (n=3) of patients were definitely~morning types, 38\% (n=57) were
moderately morning types, 59.3\% (n=89) were neither types, 0.7\% (n=1)
was moderately evening types, and no patients were definitely~evening
types. Normal distribution was observed for MEQ scores among the
participants (Figure 1).

Figure 1 near here.

According to Table 3 and 4, the mean ages of completely and moderately
morning types were greater than those of all other types. The
distribution of circadian rhythms was nearly identical between male and
female participants. Employed and unemployed individuals, as well as
patients with varying levels of education, were frequently morning and
neither types. The ANOVA test did not reveal significant associations
between chronotype and age, time of cancer onset, cancer-specific
hospitalization, chemotherapy, or radiotherapy sessions. Furthermore,
Fisher's exact test revealed no correlation between employment status,
marital status, gender, treatment methods, level of education, patient
condition, and types of circadian rhythm.

Table 3 and 4 near here.

\textbf{Discussion}

Several cancers are associated with circadian clock dysfunction,
highlighting the connection between circadian rhythm dysregulation and
oncogenesis (29). Epidemiological studies have linked cancers to night
shift work and light pollution that disrupt chronotype (2, 30). In mice,
dysregulated circadian gene expression may cause lymphoma, osteosarcoma,
and hepatocellular carcinoma (HCC), according to Kettner et al. (31).
Jiang et al. reported that circadian gene disruption is associated with
the onset of HCC~(11). Methylation of single nucleotide polymorphisms
(SNPs) or clock gene promoters is a known molecular mechanism (30).
Consideration of this issue could lead to cancer prevention and
treatment in the future.

In our study, there was no significant correlation~between chronotype
and gender (\emph{P} =0.629), age (\emph{P} =0.135), marital status
(\emph{P} =0.263), occupation (\emph{P} =0.931), or education level
(\emph{P} =0.899). Definitive and moderate morning types exhibited
higher~age means~than neither and moderate evening types. This finding
is consistent with the findings of Montaruli et al., who observed that
older adults are typically morning types, possibly due to age-related
sleep shortness, whereas younger adults are commonly evening types (32).
Furthermore, there is no correlation between age and gender, and
circadian rhythm (32, 33, 34). Some studies suggest that there may be
gender differences in circadian types due to housework, grooming, and
breakfast preparation. In a cohort study conducted by Ramin et al., the
average age and BMI of the participants were 59.2 y and 27.5
kg/m\textsuperscript{2}, respectively, and the most prevalent chronotype
was definitely morning type, while neither type was the least prevalent
(35).

Neither type increased the risk of breast cancer among participants, but
the difference was not statistically significant (35). In our study,
breast cancer was the most prevalent type, and neither type comprised
the majority, consistent with a previously published study. A
dysregulated circadian rhythm in neither species, possibly leading to
cancer, may explain this finding. Our study's mean age and BMI were 49
and 25.09 kg/m\textsuperscript{2}, respectively. All of the participants
in the current study were cancer patients; some were in advanced stages
and suffered from cachexia, which could explain the differences in BMIs.
Bhar et al. found that evening types have a higher BMI, FBS, and HbA1c,
resulting in less physical activity, unhealthy eating habits, and sleep
disturbances that lead to T2DM (33, 36).

In contrast to our study, the mean BMI is higher for morning types, but
no significant difference was observed~between circadian types (\emph{P}
=0.317). The participants lacked comorbidities such as diabetes, and we
did not evaluate their physical activity and dietary habits; as
previously mentioned, some patients were in the cachectic phase.
Chronotype was not significantly associated with duration as a cancer
patient (\emph{P} =0.855) or hospital admission (\emph{P} =0.250). The
neither and moderately evening types developed cancer sooner, were
hospitalized more frequently, experienced fatigue and weakness, and were
in advanced stages; consequently, these groups exhibit~a lower BMI. The
present study observed normal distribution for chronotype, and the mean
MEQ score was 56.6 ± 6.34 (41-74). Neither type was the most chronotype,
with the moderately evening type being the least. No evening-only types
were detected. In a case-control study conducted by Di Somma et al., the
mean MEQ score of craniopharyngioma patients was 47.8 ± 12.6 (34).

Most participants were morning types, and the minority were evening
types (34). Definitive~and moderate morning types were considered one
group, and evening types were considered a second (34). Based on the
results, females were predominantly evening and intermediate types,
while males were primarily morning types. Different MEQ means and scores
may result from the sample size, study design, and various types of
cancer. In line with our findings, Kanagarajan et al. demonstrated that
the MEQ distribution in bipolar patients aged 25 to 66 was normal, the
mean score was 49.2 ± 10.4 (24-74), neither type was the most
chronotype, and circadian rhythm was not significantly associated with
age and gender (37). The correlation between circadian rhythm and
surgery (\emph{P} =0.933), chemotherapy (\emph{P} =0.565), and
radiotherapy (\emph{P} =0.326) were not statistically significant.

Most patients who received chemotherapy and radiotherapy were neither
morning nor evening types, whereas morning types had more chemotherapy
sessions. Multiple studies have suggested that a higher MEQ score for
morning types is associated with fewer chemotherapy-related side
effects, such as nausea and vomiting (32). Cancer patients were the
subject of a case-control study by Sultan et al. (38). The participants'
mean age was 46.67 ± 12.51 y (38). Similar to our research, the majority
and minority circadian rhythms were neither morning nor evening. The MEQ
score was negatively correlated with chemotherapy-induced nausea,
vomiting, and diarrhea (38). Unfortunately, we did not assess the side
effects of chemotherapy or radiotherapy. Hematologic and non-hematologic
cancers (\emph{P} =0.999), palliative therapy or treatment (\emph{P}
=0.262), treatment method combinations such as chemotherapy +
radiotherapy (\emph{P} =0.457), chemotherapy + surgery (\emph{P}
=0.794), radiotherapy + surgery (\emph{P} =0.500), and chemotherapy +
radiotherapy + surgery (\emph{P} =0.738) were not significantly
correlated to chronotype. The majority of participants in these groups
fell into neither category.

Some research indicates that chronochemotherapy and chronoradiotherapy
may improve cancer patients' survival and response rate (18).
Consequently, chronomodulated chemotherapy or radiotherapy sessions
compatible with circadian rhythm may be advantageous to the treatment
process (18). Although a disorganized circadian rhythm may result in
carcinogenesis, cancer treatments may alter the circadian type.
Comparing the chronotype of various cancers requires additional
research.

\textbf{Study limitations}

Assessing the circadian rhythm at the time of diagnosis and then
comparing it during treatment and follow-up, studying a specific type of
cancer, not having a control group, having a small sample size, resulted
in~limited statistical power.

\textbf{Conclusion}

In conclusion, circadian rhythm distribution in our study was normal.
Indeed, cancer is a global concern, and circadian rhythm disruption as a
carcinogen is an area of study. Regulated circadian rhythm could be a
preventative measure, and targeting the clock genes could improve cancer
treatment. Chronomodulated cancer therapies are emerging fields that are
anticipated to improve prognosis. Concerning these points, additional
research is required to develop effective cancer preventive and
therapeutic interventions.

\textbf{Ethics approval and consent to participate}

Informed written consent was obtained from participants. All procedures
performed in studies

involving human participants adhered to the ethical standards of the
institutional and/or

national research committee and with the 1964 Helsinki declaration and
its later amendments

or comparable ethical standards. A copy of the written consent is
available for review by the Editor-in-Chief of this journal.

\textbf{Availability of data and material}

The datasets analyzed in the current study are available from the
corresponding author on

reasonable request

\textbf{Acknowledgements:} Authors have no acknowledgments to declare.

\textbf{Conflict of interest}

The authors declare that they have no competing interests.

\textbf{Funding}

No Funding

\textbf{Authors' contributions:} Conceptualization, N.K; Formal
analysis, G.D; Methodology, M.A and S.K; Project administration, GD and
N.K; Writing -- original draft, GD; Writing -- review \& editing, N.K,
M.A and S.K. All authors read and approved.

\textbf{References}

1. Pariollaud M, Lamia KA. Cancer in the Fourth Dimension: What Is the
Impact of Circadian Disruption? Cancer Discov. 2020;10(10):1455-64.

2. Masri S, Sassone-Corsi P. The emerging link between cancer,
metabolism, and circadian rhythms. Nat Med. 2018;24(12):1795-803.

3. Wu Y, Tao B, Zhang T, Fan Y, Mao R. Pan-Cancer Analysis Reveals
Disrupted Circadian Clock Associates With T Cell Exhaustion. Front
Immunol. 2019;10:2451.

4. Hastings MH, Reddy AB, Maywood ES. A clockwork web: circadian timing
in brain and periphery, in health and disease. Nature Reviews
Neuroscience. 2003;4(8):649-61.

5. Buhr ED, Takahashi JS. Molecular components of the Mammalian
circadian clock. Circadian clocks. 2013:3-27.

6. Albrecht U. Timing to perfection: the biology of central and
peripheral circadian clocks. Neuron. 2012;74(2):246-60.

7. Mocellin S, Tropea S, Benna C, Rossi CR. Circadian pathway genetic
variation and cancer risk: evidence from genome-wide association
studies. BMC medicine. 2018;16(1):1-8.

8. Takahashi JS. Transcriptional architecture of the mammalian circadian
clock. Nature Reviews Genetics. 2017;18(3):164-79.

9. Lamont EW, James FO, Boivin DB, Cermakian N. From circadian clock
gene expression to pathologies. Sleep medicine. 2007;8(6):547-56.

10. Liu Z, Yu K, Zheng J, Lin H, Zhao Q, Zhang X, et al. Dysregulation,
functional implications, and prognostic ability of the circadian clock
across cancers. Cancer Med. 2019;8(4):1710-20.

11. Jiang Y, Shen X, Fasae MB, Zhi F, Chai L, Ou Y, et al. The
Expression and Function of Circadian Rhythm Genes in Hepatocellular
Carcinoma. Oxid Med Cell Longev. 2021;2021:4044606.

12. Zee PC, Attarian H, Videnovic A. Circadian rhythm abnormalities.
Continuum: Lifelong Learning in Neurology. 2013;19(1 Sleep
Disorders):132.

13. Vineis P, Wild CP. Global cancer patterns: causes and prevention.
The Lancet. 2014;383(9916):549-57.

14. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A.
Global cancer statistics 2018: GLOBOCAN estimates of incidence and
mortality worldwide for 36 cancers in 185 countries. CA: a cancer
journal for clinicians. 2018;68(6):394-424.

15. Cadet J, Douki T. Formation of UV-induced DNA damage contributing to
skin cancer development. Photochemical \& Photobiological Sciences.
2018;17(12):1816-41.

16. Borrego-Soto G, Ortiz-López R, Rojas-Martínez A. Ionizing
radiation-induced DNA injury and damage detection in patients with
breast cancer. Genetics and molecular biology. 2015;38:420-32.

17. Asher G, Sassone-Corsi P. Time for food: the intimate interplay
between nutrition, metabolism, and the circadian clock. Cell.
2015;161(1):84-92.

18. Harper E, Talbot C. Is it time to change radiotherapy: the dawning
of chronoradiotherapy? Clinical Oncology. 2019;31(5):326-35.

19. Lin YM, Chang JH, Yeh KT, Yang MY, Liu TC, Lin SF, et al.
Disturbance of circadian gene expression in hepatocellular carcinoma.
Molecular Carcinogenesis: Published in cooperation with the University
of Texas MD Anderson Cancer Center. 2008;47(12):925-33.

20. Mostafaie N, Kállay E, Sauerzapf E, Bonner E, Kriwanek S, Cross HS,
et al. Correlated downregulation of estrogen receptor beta and the
circadian clock gene Per1 in human colorectal cancer. Molecular
Carcinogenesis: Published in cooperation with the University of Texas MD
Anderson Cancer Center. 2009;48(7):642-7.

21. Tokunaga H, Takebayashi Y, Utsunomiya H, Akahira J-I, Higashimoto M,
Mashiko M, et al. Clinicopathological significance of circadian
rhythm-related gene expression levels in patients with epithelial
ovarian cancer. Acta obstetricia et gynecologica Scandinavica.
2008;87(10):1060-70.

22. Flynn-Evans EE, Mucci L, Stevens RG, Lockley SW. Shiftwork and
prostate-specific antigen in the National Health and Nutrition
Examination Survey. Journal of the National Cancer Institute.
2013;105(17):1292-7.

23. Hu S, Shen G, Yin S, Xu W, Hu B. Melatonin and tryptophan circadian
profiles in patients with advanced non-small cell lung cancer. Advances
in therapy. 2009;26(9):886-92.

24. Fekry B, Eckel-Mahan K. The circadian clock and cancer: links
between circadian disruption and disease Pathology. The Journal of
Biochemistry. 2022.

25. Liu L, Ancoli-Israel S. Sleep Disturbances in Cancer. Psychiatr Ann.
2008;38(9):627-34.

26. Taillard J, Philip P, Chastang JF, Bioulac B. Validation of Horne
and Ostberg morningness-eveningness questionnaire in a middle-aged
population of French workers. J Biol Rhythms. 2004;19(1):76-86.

27. Zencirci AD, Arslan S. Morning-evening type and burnout level as
factors influencing sleep quality of shift nurses: a questionnaire
study. Croatian medical journal. 2011;52(4):527-37.

28. Rahafar A, SADEGHI JM, Sadeghpour A, Mirzaie S. Surveying
psychometric features of Persian version of morning-eventide
questionnaire. 2013.

29. Tsuchiya Y, Umemura Y, Yagita K. Circadian clock and cancer: From a
viewpoint of cellular differentiation. International Journal of Urology.
2020;27(6):518-24.

30. Verlande A, Masri S. Circadian Clocks and Cancer: Timekeeping
Governs Cellular Metabolism. Trends Endocrinol Metab. 2019;30(7):445-58.

31. Kettner NM, Voicu H, Finegold MJ, Coarfa C, Sreekumar A, Putluri N,
et al. Circadian homeostasis of liver metabolism suppresses
hepatocarcinogenesis. Cancer cell. 2016;30(6):909-24.

32. Montaruli A, Castelli L, Mulè A, Scurati R, Esposito F, Galasso L,
et al. Biological Rhythm and Chronotype: New Perspectives in Health.
Biomolecules. 2021;11(4).

33. Barrea L, Muscogiuri G, Pugliese G, Modica R, Laudisio D, Aprano S,
et al. Chronotype: what role in the context of gastroenteropancreatic
neuroendocrine tumors? Journal of Translational Medicine.
2021;19(1):324.

34. Di Somma C, Scarano E, Barrea L, Solari D, Riccio E, Arianna R, et
al. Craniopharyngioma, Chronotypes and Metabolic Risk Profile.
Nutrients. 2021;13(10).

35. Ramin C, Devore EE, Pierre-Paul J, Duffy JF, Hankinson SE,
Schernhammer ES. Chronotype and breast cancer risk in a cohort of US
nurses. Chronobiol Int. 2013;30(9):1181-6.

36. Bhar D, Bagepally BS, Balachandar R. Association between Chronotype
and Diabetes mellitus: A systematic Review and Meta-analysis. Available
at SSRN 3863174. 2021.

37. Kanagarajan K, Gou K, Antinora C, Buyukkurt A, Crescenzi O, Beaulieu
S, et al. Morningness-Eveningness questionnaire in bipolar disorder.
Psychiatry research. 2018;262:102-7.

38. Sultan A, Taj S, Choudhary V, Parganiha A. Predictive role of
socio-demographic and chronotype on health-related quality of life of
cancer patients from southeastern India. Biological Rhythm Research.
2022;53(4):592-607.

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