Sleep duration and incidence of colorectal cancer in postmenopausal women.

Both short and long sleep durations have been associated with increased risk of obesity, diabetes, cardiovascular disease, as well as all-cause mortality (Gallicchio and Kalesan, 2009; Parish, 2009). However, the association between habitual sleep duration and the risk of commonly occurring cancers is largely unknown. Earlier studies hypothesised that electric light at night disrupts the circadian rhythm and impairs the secretion of the pineal hormone melatonin. Nocturnal suppression of melatonin may lead to an elevation of circulating oestrogen levels (Stevens and Davis, 1996). Therefore, many studies have examined night shift work or rotating shift work in association with the risk of hormone-related cancers (Conlon et al, 2007; Kolstad, 2008; Poole et al, 2011). The International Agency for Research on Cancer (IARC) evaluated experimental and epidemiologic evidence of the association between shift work and various cancers (IARC, 2010). The panel concluded that there was sufficient experimental evidence from animal studies that have demonstrated that light at night can substantially promote the development of different types of tumours. There was consistent evidence for an association between night shift work and breast cancer in adequately designed epidemiologic studies; however, the evidence for other types of cancer was very limited owing to inconsistent study findings. Therefore, IARC classified ‘shift work that involves circadian disruption' as a ‘probably carcinogenic to human (group 2A)'(IARC, 2010; Straif et al, 2007). Recent studies, including a few genome-wide association studies, have implicated circadian rhythm in various aspects of carcinogenesis, including DNA damage response, DNA repair, glucose metabolism and immune suppression (Bass and Takahashi, 2010; Dupuis et al, 2010; Sancar et al, 2010; Froy, 2011). Several lines of evidence suggest a potential role of circadian rhythm in colorectal cancer (CRC) development (Wood et al, 2008; Alhopuro et al, 2010; Basterfield and Mathers, 2010). For example, inactivation of the Period 2 gene accelerated intestinal and colonic tumorigenesis in Apc(Min/+) mice (Wood et al, 2008). In the Min mice, strong significant positive correlations between sleep duration and both tumour multiplicity and burden were observed (Basterfield and Mathers, 2010). In humans, somatic mutations of the CLOCK gene have been frequently found in microsatellite-instable CRC (Alhopuro et al, 2010). In spite of enhanced understanding on the physiology of circadian rhythm in metabolism homeostasis and colorectal tumorigenesis, habitual sleep duration, an important and potentially modifiable lifestyle factor, in association with CRC has not been examined in population-based studies. We therefore tested the hypothesis that sleep duration is associated with the risk of CRC in a large cohort of postmenopausal women. As hormone replacement therapy (HRT) has been shown to improve sleep quality in postmenopausal women (Polo-Kantola et al, 1998; Welton et al, 2008), we performed an a priori analysis to test the interaction between HRT and sleep duration. In addition, we examined the association between other sleep habits and risk of CRC.