Dissertation committee:
Κατσάμπας Ανδρέας, Ομότιμος Καθηγητής, Ιατρική Σχολή ΕΚΠΑ
Γεωργάλα Σοφία, Ομότιμη Καθηγήτρια, Ιατρική Σχολή ΕΚΠΑ
Ρηγόπουλος Δημήτριος, Καθηγητής, Ιατρική Σχολή ΕΚΠΑ
Στρατηγός Αλέξανδρος, Καθηγητής, Ιατρική Σχολή ΕΚΠΑ, Επιβλέπων
Νικολαΐδου Ηλέκτρα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή ΕΚΠΑ
Κατούλης Αλέξανδρος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή ΕΚΠΑ
Γρηγορίου Σταμάτιος, Επίκουρος Καθηγητής, Ιατρική Σχολή ΕΚΠΑ
Summary:
Background: Recent data have shown an inverse association between serum 25-hydroxyvitamin D concentration and incidence of several cancers, including cutaneous malignant melanoma (CMM). In addition, lower serum 25-hydroxyvitamin D levels have been associated with thicker or higher stage melanomas and worse survival in observational studies.
Materials and Methods: Ninety-nine patients diagnosed with primary CMM and 97 matched healthy controls entered the study. Demographic characteristics, risk factors for CMM, and clinical and histological characteristics were recorded for patients with primary CMM. Total serum 25-hydroxyvitamin D levels of melanoma patients measured by fully automated chemiluminescent vitamin D total immunoassay (Elecsys vitamin D total, Roche) at the time of diagnosis were compared with those of healthy controls. In addition, we tested the association of serum total 25-hydroxyvitamin D levels at melanoma diagnosis with known risk and prognostic factors for CMM.
Results: Of the melanoma patients, 49 (49.49%) had deficient serum total 25-hydroxyvitamin D levels (<20 ng/mL), 23 (23.23%) had insufficient levels (21-29 ng/mL), and 27 (27.27%) had adequate of matched healthy controls. In addition, we tested the association of serum 25-hydroxyvitamin D levels at the time of melanoma diagnosis with known risk and prognostic factors for CMM, in an attempt to assess their prognostic value.
Materials and Methods
Study Design
This prospective cohort study was conducted at the Melanoma Unit of the First Department of Dermatology and Venereology, Andreas Syggros Hospital, Athens, Greece. The study was approved by the ethics committee of the hospital. Written informed consent was obtained for all entered patients and controls. Patient recruitment took place from April 2011 to
March 2014. Consecutive patients diagnosed with primary invasive CMM of any stage were enrolled. The diagnosis of CMM was made on histological grounds. Exclusion criteria included the following: patients with noncutaneous melanoma or metastatic melanoma of unknown primary; patients with self-reported preexisting conditions that could interfere with vitamin D metabolism, such as chronic liver or kidney disease; transplant recipients or those with other causes of immunosuppression; patients receiving high-dose calcium therapy; and patients receiving vitamin D supplementation during the previous 6 months.
For all recruited melanoma patients, complete personal and family history was obtained and total body skin examination was performed. Demographic characteristics such as age, sex, race, occupation; body measurements, ie, height and weight to calculate body mass index (BMI); risk factors for CMM including hair color, skin color, skin phototype, occupational and recreational sun exposure, sunburns during childhood; presence of dysplastic nevi, number of melanocytic nevi, personal or family history of CMM, have all been recorded. Clinical type of CMM and localization in sun-exposed or sun-protected areas were assessed. Breslow thickness and presence or absence of ulceration were obtained from the histology report at the time of diagnosis. For CMM staging, the seventh edition of the American Joint Committee on CanIntroduction
The incidence of cutaneous malignant melanoma (CMM) has increased steeply over recent decades and continues to grow worldwide despite intense efforts at primary prevention.
CMM results from complex interactions between genetic and environmental factors. Excessive intermittent ultraviolet radiation (UVR) exposure and sunburns during childhood are considered as the principal causes of CMM insurgence in adults, with double the risk relative to a nonexposed population [1,2].
On the other hand, UVR stimulates the endogenous production of pre-vitamin D3
in the skin, which supplies >90% of the body’s requirements [3]. In vivo vitamin D demonstrates pleiotropic effects. Beyond its role in homeostasis of calcium and phosphorus, it modulates cellular functions, such as innate and adaptive immunity through the suppression of inflammation, cell proliferation, differentiation, apoptosis, and metastatic potential [4-8]. Recent data have linked low serum vitamin D levels to a wide range of diseases, including cardiovascular disease, insulin resistance, autoimmune disease, and infection. Most importantly, they have been linked with increased incidence of several malignancies, such as breast, colorectal, kidney, lung, and pancreatic cancer [6-10].
The relationship between vitamin D levels and CMM seems to be more intricate, compared with other malignancies [1]. Vitamin D receptor is present in normal melanocytes and in certain cell lines of melanoma [11]. In vitro studies have shown that a proportion of melanoma cell lines in culture respond to the antiproliferative effect of active vitamin D analogs [12,13]. Serum vitamin D levels have been examined as a marker for increased risk for CMM development. Lower serum vitamin D levels have been associated with thicker or higher stage melanomas [14-20]. Two recent large cohort studies have shown that vitamin D levels were significantly associated with overall survival, melanoma-specific survival, and disease-free survival [21,22].
In the present study, we sought to investigate serum total 25-hydroxyvitamin D levels in a cohort of patients diagnosed with primary CMM and compare them with those levels (>30 ng/mL). The median serum total 25-hydroxyvitamin D levels were significantly lower in melanoma patients (20.62 ng/mL) compared with healthy controls (24.71 ng/mL), but statistical significance was not reached (chi-square test, P = 0.051) No statistically significant association was found between serum total 25-hydroxyvitamin D levels and demographic characteristics; risk factors for
CMM; prognostic factors, such as Breslow thickness and ulceration; as well as clinical characteristics, such as melanoma stage, clinical type, and location.
Conclusions: Lower serum 25-hydroxyvitamin D levels were found in our Greek cohort of melanoma patients compared with healthy controls, without reaching, however, statistical significance; these levels were not statistically associated with established risk and prognostic factors for CMM.
