Clock-cancer connection in non-Hodgkin’s lymphoma

Abstract

The universal 24-hour circadian clock has a profound impact on many daily biological processes. Disturbance of circadian rhythms has been implicated in the etiologies of many chronic illnesses, including cancer; with correlations most profoundly found among hormone-related breast and prostate cancers. Given the fact that circadian disruption can cause immune deregulation, which is so far the only established risk factor for non-Hodgkin's lymphoma (NHL), we hypothesize that altered circadian rhythms due to environmental factors and/or genetic variations in genes responsible for maintaining circadian rhythms may result in the deregulation of clock-associated biological processes such as immune responses and activities, and consequently influence an individual's risk of developing NHL. Our recent findings provided the first molecular epidemiological evidence linking a major circadian gene to NHL and warrant further investigation. Confirmation of this hypothesis will further add to our understanding of the role of the circadian clock in lymphomagenesis and facilitate the development of novel risk and prognostic biomarkers for NHL.

Night shift work and chronic lymphocytic leukemia in the MCC‐Spain case–control study

“…4 Alterations in expression levels and/or polymorphisms in several "clock" genes, such as Cry1, Cry2, Bmal1, Per1 and Per2 among others, have been associated with lymphoma and CLL etiology and prognosis. [5][6][7][8] Furthermore, serum melatonin levels, which vary with daylight exposure, were significantly lower in CLL subjects as compared with healthy controls in a recent study based on 37 CLL cases. 6 These evidences suggest that circadian disruption by night shift work exposure may have an influence on CLL etiology, but to our knowledge, no epidemiological study has examined it yet.…”

“…Alterations in expression levels and/or polymorphisms in several “clock” genes, such as Cry1 , Cry2 , Bmal1 , Per1 and Per2 among others, have been associated with lymphoma and CLL etiology and prognosis . Furthermore, serum melatonin levels, which vary with daylight exposure, were significantly lower in CLL subjects as compared with healthy controls in a recent study based on 37 CLL cases .…”

Clock-Cancer Connection in Non–Hodgkin's Lymphoma: A Genetic Association Study and Pathway Analysis of the Circadian Gene Cryptochrome 2

“…Several observational studies indicate that individuals who do not maintain a normal sleep/wake cycle may be at increased risk for several cancer types, and after considering evidence from epidemiologic and experimental studies, the International Agency for Research on Cancer (IARC) recently concluded that shift work that involves circadian disruption is “probably carcinogenic to humans” (2). Although much of the current epidemiologic evidence has focused on breast cancer, it has recently been hypothesized that circadian disruption may also affect risk for NHL, possibly through its influence on immune regulation (3). …”

Circadian Gene Polymorphisms Associated with Breast Cancer Susceptibility

“…There are a few studies on circadian gene variants in shift workers and susceptibility to breast carcinogenesis [11,12]. Molecular epidemiological studies reveal a significant association of the polymorphic variants of circadian genes and the risk of various cancer types such as breast cancer [13,14,15,16,17], colorectal cancer [18,19,20], glioma [21], prostate cancer [22,23], hepatocellular carcinoma [24,25], lung cancer [26], non-Hodgkin’s lymphoma [27], as well as mood [28,29] and metabolic disorders [30].…”