Surrogates of Long-Term Vitamin D Exposure and Ovarian Cancer Risk in Two Prospective Cohort Studies

Abstract

Experimental evidence and ecologic studies suggest a protective role of vitamin D in ovarian carcinogenesis. However, epidemiologic studies using individual level data have been inconsistent. We evaluated ultraviolet (UV)-B radiation, vitamin D intake, and predicted plasma 25-hydroxyvitamin D [25(OH)D] levels as long-term surrogates of vitamin D exposure within the Nurses’ Health Study (NHS) and NHSII. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of overall ovarian cancer and by histologic subtype using Cox proportional hazards models. Between 1976 and 2010 in NHS and 1989 and 2011 in NHSII, we identified a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255) over 4,628,648 person-years of follow-up. Cumulative average UV-B exposure was not associated with ovarian cancer risk in NHS (Ptrend = 0.08), but was associated with reduced risk in NHSII (highest vs. lowest category RR = 0.67; 95% CI: 0.50, 0.89; Ptrend < 0.01). When stratified by histologic subtype, UV-B flux was positively associated with risk of serous tumors in NHS (Ptrend < 0.01), but inversely associated in NHSII (Ptrend = 0.01). Adjusted for confounders, ovarian cancer risk was not associated with vitamin D intake from food or supplements or with predicted 25(OH)D levels. Our study does not strongly support a protective role for vitamin D in ovarian cancer risk.

Epidemiology of ovarian cancer: a review

“…However, epidemiological evidence that vitamin D status influences OC risk is inconsistent. One systemic review concluded that there is no strong evidence that vitamin D decreases risk 260 and a meta-analysis of ten longitudinal studies 261 as well as other cohort studies 262 reached a similar conclusion. In the meta-analysis the protective effect was evident in seven of the ten studies and the pooled estimate was a 17% reduced risk with increasing 25(OH)D levels; however, the pooled estimate was not statistically significant (RR = 0.83, 95% CI: 0.63–1.08) 261 .…”

Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study

“…5 Several recent studies have examined whether or not serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with ovarian cancer risk or mortality. [6][7][8][9][10][11][12] Vitamin D is produced in the skin when 7-dehydrocholesterol is exposed to Ultraviolet B. It is transported to the liver, where it is hydroxylated to become 25(OH)D. It then undergoes a second hydroxylation step, primarily in the liver, to become the active form, 1,25-dihydroxyvitamin D (calcitriol).…”

Vitamin D Exposure and Ovarian Cancer Risk and Prognosis

“…A total of 350 independent articles on ovarian cancer incidences were found, among which 93 were judged to be eligible for full-text review (Figure 1). Seventeen articles met our inclusion criteria [14,[27][28][29][30][31][32][38][39][40][41][42][43][44][45][46][47], of which nine had been included in a previous systematic review [13] and four in a previous meta-analysis [15]. Two articles reported the results of pooled analyses [14,41], which included some individual studies on vitamin D exposure and ovarian cancer that had not been previously published.…”

“…Two articles reported the results of pooled analyses [14,41], which included some individual studies on vitamin D exposure and ovarian cancer that had not been previously published. Of the 17 eligible studies, vitamin D was assessed according to sun exposure in four studies [27][28][29]31], dietary intake in 10 studies [28][29][30][39][40][41][42][43][44][45] and circulating 25(OH)D levels in five studies [14,32,38,46,47]. For ovarian cancer survival, a total of 281 independent articles were found, of which 47 were judged to be eligible for full-text review and three were retained ( Figure 2) [33][34][35].…”

“…Overall, there is biologic plausibility for a relation between vitamin D and ovarian cancer, which is supported by experimental research, but the epidemiological evidence remains unclear. Since the three previous reviews [13][14][15], there have been six additional studies published on vitamin D and ovarian cancer risk [27][28][29][30][31][32], as well as three studies on the relation between vitamin D and ovarian cancer survival [33][34][35]. We carried out a systematic narrative review of the literature on vitamin D and ovarian cancer risk and survival to summarize the literature to date.…”