Higher levels of vitamin D, even within the normal range, were associated with increased risk for nonmelanoma skin cancer, data indicates.

Participants in a prospective cohort study who had higher serum 25-hydroxyvitamin D (25-OHD) levels, a marker of vitamin D intake and storage, were more likely to develop squamous cell and basal cell carcinomas, according to Melody J. Eide, MD, MPH, of Henry Ford Hospital in Detroit, and colleagues.

However, the researchers acknowledged that the relationship between vitamin D levels and sunlight exposure is complex — exposure to ultraviolet B light is known to cause skin cancer, but also plays a role in the cutaneous synthesis of vitamin D — making it difficult to interpret the findings.

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“The direct relationship of UV exposure with both vitamin D and nonmelanoma skin cancer makes it a likely profound confounder in this, and other studies,” the researchers wrote.

Earlier studies have, in fact, yielded conflicted findings, with some suggesting that vitamin D reduces the risk for basal cell carcinoma and others, the opposite.

In an attempt to reach a conclusion, Eide and colleagues enrolled a cohort of 3,223 white HMO members with a high probability of developing nonmelanoma skin cancer.

Participants had sought medical advice about osteoporosis risk between January 1997 and December 2001, thus their assessment included information on serum 25-OHD levels. A total of 2, 257 were vitamin D deficient, as defined by 25-OHD levels less than 30 ng/mL of serum.

The researchers then used the HMO claims database to track incident cases of basal cell and squamous cell carcinomas during a mean 9.8-year follow-up period. They identified 240 patients with nonmelanoma skin cancer, 49 with squamous cell carcinoma and 163 with basal cell carcinoma. The majority of cases, 80%, occurred in frequently sun-exposed skin such as the face, scalp, neck and hands.

Patients were divided into four groups based on their 25-OHD levels. Comparing those participants in the lowest quartile to those in the highest (less than 19 ng/mL of serum vs. 31 ng/mL or higher) revealed that those in the uppermost quartile were significantly more likely to develop nonmelanoma skin cancer (OR=1.6; 95% CI: 1.1-2.3).

Similar outcomes were observed in a logistic regression analysis assessing risk for cancer with 25-OHD levels just above the cutoff for vitamin D deficiency of less than 15 ng/mL of serum:

For both squamous cell and basal cell carcinomas, the adjusted OR was 1.8 (95% CI: 1.1-2.9; P<0.05)

For squamous cell carcinoma only, the OR was 1.7, but did not reach statistical significance with a wide 95% CI of 0.7 to 4.0

For basal cell carcinoma, the OR was also 1.7, but was statistically significant at P<0.05 (95% CI: 1.00-2.9)

These findings are a “notable contribution to the limited and conflicting epidemiological investigation regarding the relationship between vitamin D and nonmelanoma skin cancer,” the researchers concluded.

Study limitations include the inability to assess other risk factors including individual sun exposure and family history, the researchers noted. They also acknowledged that the all white, mostly female population is not representative.

“In the future, analysis of a prospective cohort that is representative of the general population, ideally with available UV-exposure estimates, risk factor and dietary supplemental vitamin D information, is essential to further elucidate the highly complex relationship between vitamin D and nonmelanoma skin cancer.

Eide MJ et al. Arch Dermatol. 2011;doi:10.1001/archdermatol.2011.231.