Re: "Low 25-hydroxyvitamin D concentrations may explain the link between breast cancer risk and shift work".

Evidence concerning the association between night shift work and serum vitamin D concentrations is scarce and inconsistent. According to a cross-sectional study of the 1958 British birth cohort, night workers have significantly lower 25(OH)D levels compared with others (Ward et al. 2011). However, Itoh and colleagues reported no significant difference in serum 25(OH)D levels between daytime workers and night shift workers (Itoh et al. 2011). Moreover, no study has been conducted to compare the prevalence of vitamin D deficiency between night workers and non-night workers. A cross-sectional study conducted over 83 young shift-working nurses in Kingston General Hospital in Canada found that approximately 10 % of nurses have vitamin D deficiency (Wallingford et al. 2014). However, it is reported that approximately 40 % of adult participants were deficient in vitamin D based on data from the National Health and Nutrition Examination Survey 2005– 2006 (Forrest and Stuhldreher 2011). In conclusion, the underlying mechanism between circadian disruption and breast cancer is complicated. It remains possible that lower serum 25(OH)D levels may be responsible, in part, for the relationship between circadian disruption and breast cancer. However, the existing evidence concerning a relationship between vitamin D status and breast cancer risk is inconclusive. Large prospective observational studies and randomized controlled trials are required to justify the causal relationship between vitamin D deficiency and breast cancer risk in women. In addition, rigorous studies are needed for assessment of association of night work with vitamin D deficiency. In our paper (He et al. 2014), mechanisms concerning circadian disruption on breast cancer risk are not extensively discussed because of a lack of conclusive evidence, although we considered suppression in melatonin secretion as a possible pathway towards development of breast cancer in women. In Grant’s letter, the author suggested decreased 25(OH)D levels in blood as an alternate hypothesis linking circadian disruption to breast cancer risk in women. The exact mechanism between circadian disruption and breast cancer is complicated. A body of evidence suggests that lower serum 25(OH)D concentrations are positively related to breast cancer risk in women. Hence, we think that Grant’s letter is warranted. The relationship between vitamin D and breast cancer has been extensively studied. A dose–response metaanalysis by Bauer et al. (2013) found a nonlinear inverse association between circulating 25(OH)D levels and breast cancer among postmenopausal women. Similarly, Chen et al. (2010) revealed a positive association of vitamin D with breast cancer risk based on results of a metaanalysis summarizing data from five case–control and six cohort studies. However, inconsistent results were reported by another meta-analysis (Gandini et al. 2011) and a large prospective study based on data from the Third National Health and Nutrition Examination Survey (Freedman et al. 2007). Additionally, evidence from clinical trials of vitamin D supplementation in relation to breast cancer has been inconclusive and only slight benefits from supplementation have been observed (Redaniel et al. 2014).