Based on PubMed | Does a low 25-hydroxyvitamin D test result indicate increased risk or poorer prognosis in endometrial cancer?

Low 25‑hydroxyvitamin D and endometrial cancer risk or prognosis

Based on the best available prospective human data, low blood levels of 25‑hydroxyvitamin D (25[OH]D) have not been shown to increase the risk of developing endometrial cancer, and evidence that vitamin D status affects prognosis after diagnosis is currently insufficient. ^{[1] [2]}

What the strongest studies show

• Large pooled nested case–control analysis: In a consortium analysis pooling 7 cohorts (830 cases, 992 controls), circulating 25(OH)D showed no association with endometrial cancer risk after adjusting for body mass index. ^[1] Compared with the reference category (50–<75 nmol/L), the odds ratio was 1.08 for <25 nmol/L and 0.90 for ≥100 nmol/L, with no trend across categories. ^[1]

• Prospective cohort with time‑varying vitamin D estimate: In the Nurses’ Health Study (644 incident cases), neither predicted plasma 25(OH)D nor total dietary vitamin D intake was associated with endometrial cancer incidence. ^[2] Genetic variants in vitamin D–related genes also showed no significant association with risk. ^[2]

These prospective designs reduce recall bias and establish temporality, which makes their null findings particularly informative for risk assessment. ^{[1] [2]}

Interpreting this for risk and prognosis

• Risk: While laboratory and ecological hypotheses have suggested vitamin D could reduce gynecologic cancer risk, the best prospective epidemiologic evidence to date does not support a protective effect of higher 25(OH)D against endometrial cancer. ^{[1] [2]} It’s also notable that obesity is a strong risk factor for endometrial cancer and is inversely associated with 25(OH)D, so careful adjustment as done in these studies matters. ^{[1] [2]}

• Prognosis: High‑quality, prospective data directly linking pre‑ or post‑diagnosis 25(OH)D levels to endometrial cancer outcomes (recurrence, survival) are limited, and no definitive association has been established. ^{[1] [2]} Current evidence does not justify using vitamin D status as a prognostic biomarker in endometrial cancer care. ^{[1] [2]}

Practical takeaways for clinicians and individuals

• Maintain general vitamin D health: It’s reasonable to optimize vitamin D for bone and overall health, but not specifically to prevent endometrial cancer or to improve its prognosis, given current evidence. ^{[1] [2]}

• Focus on established risk factors: Weight management, management of unopposed estrogen exposure, and attention to metabolic health remain key modifiable levers for endometrial cancer risk, whereas vitamin D does not appear to be a major driver. ^{[1] [2]}

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Summary table

Question	Current evidence	Bottom line
Does low 25(OH)D increase endometrial cancer risk?	Two large prospective analyses found no association between 25(OH)D and incidence after proper adjustment. [1] [2]	No clear link to higher risk; raising 25(OH)D solely for risk reduction is not supported.
Does low 25(OH)D worsen prognosis after diagnosis?	High‑quality prospective data are insufficient, and no definitive association has been shown. [1] [2]	No validated prognostic role for vitamin D levels at this time.

Key citations

• Cohort Consortium Vitamin D Pooling Project: No association between circulating 25(OH)D and endometrial cancer risk after BMI adjustment; null across categories. ^[1]

• Nurses’ Health Study: No association between predicted plasma 25(OH)D or dietary vitamin D and incident endometrial cancer; vitamin D–related SNPs also null. ^[2]