Chronotype: what role in the context of gastroenteropancreatic neuroendocrine tumors?

Abstract

Background: Chronotype is defined as a trait determining the subject circadian preference in behavioral and biological rhythms relative to external light-dark cycle. Although individual differences in chronotype have been associated with an increased risk of developing some types of cancer, no studies have been carried out in gastroenteropancreatic neuroendocrine tumors (GEP-NET).

Materials: We investigate the differences in chronotype between 109 GEP-NET and 109 healthy subjects, gender-, age-, and BMI-matched; and its correlation with tumor aggressiveness.

Results: GEP-NET patients have a lower chronotype score (p = 0.035) and a higher percentage of evening chronotype (p = 0.003) than controls. GEP-NET patients with morning chronotype had lower BMI, waist circumference, and higher percentage of MetS (p < 0.001) than evening type. Interestingly, considering the clinical pathological characteristics, patients with the presence of metastasis, grading G2, and in progressive disease presented the lower chronotype score (p = 0.004, p < 0.001, and p = 0.002; respectively) compared to other categories. Chronotype score was negatively associated with anthropometric measurements, metabolic profile, percentage of MetS, and Ki67 index (p < 0.001 for all).

Conclusions: GEP-NET patients have an unhealthy metabolic profile and present more commonly an evening chronotype. These results support the importance of including the assessment of chronotype in an adjunctive tool for the prevention of metabolic alterations and tumor aggressiveness of GEP-NET.

Keywords: Chronotype; Diet; Gastroenteropancreatic tumors (GEP-NET); Metabolic syndrome (MetS); Nutrition; Nutritionist; Tumor aggressiveness.

Fig. 1

The individual differences in chronotype score and percentage of chronotype in GEP-NET patients compared to the control group. GEP-NET patients have a lower chronotype score and a higher percentage of evening chronotype than controls. In addition, grouped GEP-NET patients according to chronotype categories, most of the participants had a morning chronotype (n = 53, 48.6%), followed by evening type (n = 37, 33.9%), and finally the neither chronotype (n = 19, 17.4%). Difference in chronotype score was analysed by paired Student’s t test, while differences in chronotype categories were analysed by chi-square (χ²) test. *A p value in bold type denotes a significant difference (p < 0.05). GEP-NET, gastroenteropancreatic-neuroendocrine tumors

Fig. 2

Chronotype score in GEP-NET patients according to the clinical pathological characteristics. Metastatic stage, grading G2 and progressive disease presented the lower chronotype score (p = 0.004, p < 0.001, and p = 0.002; respectively) compared to other categories of the clinical pathological characteristics. Differences in metastasis and grading were analysed by paired Student’s t test, while ANOVA test, with the Bonferroni test as post-hoc test was used to evaluate differences in progressive disease. *A p value in bold type denotes a significant difference (p < 0.05). G, grading

Fig. 3

ROC for the value of chronotype score predictive of the presence of metastasis. In the ROC analysis, the threshold value of chronotype score predicting of the presence of metastasis was found at ≤ 38. *A p value in bold type denotes a significant difference (p < 0.05)

Fig. 4

ROC for the value of chronotype score predictive of the highest grading (G2). In the ROC analysis, the threshold value of chronotype score predicting the highest grading (G2) was found at ≤ 54. *A p value in bold type denotes a significant difference (p < 0.05)

Fig. 5

ROC for the value of chronotype score predictive of the highest progressive disease. In the ROC analysis, the threshold value of chronotype score predicting the highest progressive disease was found at ≤ 37. *A p value in bold type denotes a significant difference (p < 0.05)