AS346 - Serum 25-hydroxyvitamin D Levels and Risk of Developing Melanoma

This page provides study documentation for AS346. For description of the specimen results, see Specimen Results Description (open to public). Data sets of the specimen results are included in the existing WHI datasets located on the WHI Data on this site (sign in and a completed Data Distribution Agreement are required; see details on the Data site).

Investigator Names and Contact Information

Jean Tang []


Purpose: To conduct a nested case-control study to determine whether higher baseline 25-hydroxyvitamin D serum levels are associated with reduced melanoma risk in Women's Health Initiative (WHI) women who have been followed for 10 years.

Background: Melanoma has steadily increased in incidence over the past 50 years, and is now the 7th most common cancer diagnoses among women. Studies have shown a significant relationship between higher 25-hydroxyvitamin D [abbreviated 25(OH)D] serum levels and thinner melanomas at presentation, as well as increased relapse-free survival and decreased risk of metastasis. Other studies have suggested no association between 25(OH)D serum levels and melanoma risk, but were limited by small sample size, geographical homogeneity, and lack of serum standardization. We have found that WHI CaD participants with low 25(OH)D levels have a 4-5 fold higher risk compared to women with normal levels (P<0.01, unpublished).  This small study was limited by the number of few melanoma cases among participants with 25(OH)D levels already measured in other ancillary studies (N=27 melanoma cases out of 4,868 serum samples). In this proposal, we will determine whether higher baseline 25(OH)D serum levels are associated with a reduced risk of melanoma in post-menopausal women in a much larger sample of melanoma cases and controls.

Methodology: In this study, we will measure baseline 25(OH)D serum levels in stored serum samples from 700 white women with melanoma and 700 matched controls within the WHI OS cohort using LC-mass spectrometry. We will then perform multivariate logistic regression to determine whether a relationship exists between baseline serum levels of 25(OH)D and melanoma risk by accounting for the women's baseline characteristics, skin cancer risk factors, and evaluating for a dose-response association. The independent variable will be presence/absence of melanoma, and the dependent variables will be baseline 25(OH)D, age, prior skin cancer history and other confounders of vitamin D levels (geographic location, outdoor physical activity, season of blood draw, BMI, dietary vitamin intake). Our hypothesis is that higher levels of 25(OH)D, greater than 30 ng/mL, will be associated with a 1.4-fold reduced melanoma risk in post-menopausal women. These findings could affect future recommendations for vitamin D intake in at-risk women.

Specific Aims

Our research goal is to conduct a case-control study to determine the association between baseline serum levels of 25-hydrovitamin D [25(OH)D] and incident melanoma risk. WHI women who have had a prior NMSC and who were randomized to receive calcium plus vitamin D have a reduced risk of melanoma.1 WHI CaD women with low 25(OH)D levels have a 4-5 fold higher melanoma risk, however these data are preliminary and from a limited sample set (N=27 melanoma cases vs. 4,868 controls). We hypothesize that post-menopausal women with higher 25(OH)D serum levels will have a reduced risk of melanoma in the entire WHI OS cohort.  


Aim 1: Measure baseline 25(OH)D levels from 700 women diagnosed with melanoma and 700 matched controls within the Women's Health Initiative OS cohort using LC-mass spectrometry.

Aim 2: Compare baseline characteristics and risk factors of both groups.

Aim 3: Analyze 25(OH)D levels and the relationship to melanoma in a dose-response manner.​