Erratum: Why vitamin D for cancer patients?

[This corrects the article on p. 1 in vol. 3.].

Why vitamin D for cancer patients?

UNLABELLED: Several epidemiological, pre-clinical and clinical studies support Vitamin D as a preventive and therapeutic cancer agent. BACKGROUND: Vitamin D and cancer: calcitriol, the biologically active form of vitamin D (1,25(OH)D), exerts its effects mainly through binding to nuclear vitamin D receptor (VDR). Calcitriol has been shown to be an anti-proliferative, pro-differentiation, pro-apoptotic agent and an inhibitor of cell migration. Animal and human in vitro studies strongly indicate that vitamin D may have benefits for many forms of cancer. Inadequate levels of circulating 25-hydroxy-vitamin D (25(OH)D) are associated with an increased risk and poor prognosis of several types of cancer. Vitamin D and melanoma: cutaneous malignant melanoma (CMM) represents a major public health issue: rates in Italy have almost doubled in the last decade and CMM is frequent among young adults. For resected stage II melanoma no standard adjuvant treatment exists and five-year overall survival is about 70%. Cultured melanoma cells can synthesize calcitriol from 25(OH)D and express the VDR. Moreover, 1,25(OH)D has anti-proliferative and pro-differentiation effects in human melanoma cells. 1,25(OH)D has been shown to induce apoptosis in human melanoma cell lines and has an inhibitory effect on the spreading of melanoma cells in vitro. Preliminary results on vitamin D: epidemiological data indicate that vitamin D deficiency is relatively common in Europe. In an Italian study, we found that 85% of the participants had insufficient levels of 25(OH)D. We have shown through a meta-analysis of randomized trials that vitamin D supplementation is associated with a significant reduction (7%) in total mortality in healthy subjects and an association between VDR and 25(OH)D and CMM progression has also been demonstrated. We have also reported significant associations between VDR polymorphisms and incidence of skin cancer. In early supplementation trials, the lack of effect on cancer incidence has been attributed to insufficient vitamin D supplementation, stressing the need to better study vitamin D bioavailability. In fact, a recent IARC report highlighted the need for new randomized trials, based on results from our meta-analyses on 25(OH)D serum levels and cancer risk. Clinical trial and biomarkers studies: in order to assess whether vitamin D supplementation could improve prognosis of CMM, an Italian multi-centre trial in stage II resected melanoma patients was planned to monitor changes in 25(OH)D. The study will address two important questions regarding the relationship between the biology of VDR and (1) vitamin D metabolism, and (2) CMM prognosis. This will involve investigating the association between VDR polymorphisms and Breslow thickness, the most important prognostic factor of CMM, and between 25(OH)D serum level, vitamin D supplementation and VDR. We will also evaluate at baseline whether VDR polymorphisms are associated with Breslow thickness and whether we obtain significant increase in 25(OH)D serum levels during the first year of supplementation. We will quantify the percentages of patients who have desirable levels of 25(OH)D and, if they don't, the mean time to reach that level. The findings from this study will be of great interest because vitamin D could have anti-cancer benefits for a wide spectrum of cancers.

Body mass index as a predictor of fracture risk: a meta-analysis.

Low body mass index (BMI) is a well-documented risk factor for future fracture. The aim of this study was to quantify this effect and to explore the association of BMI with fracture risk in relation to age, gender and bone mineral density (BMD) from an international perspective using worldwide data. We studied individual participant data from almost 60,000 men and women from 12 prospective population-based cohorts comprising Rotterdam, EVOS/EPOS, CaMos, Rochester, Sheffield, Dubbo, EPIDOS, OFELY, Kuopio, Hiroshima, and two cohorts from Gothenburg, with a total follow-up of over 250,000 person years. The effects of BMI, BMD, age and gender on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson regression model in each cohort separately. The results of the different studies were then merged. Without information on BMD, the age-adjusted risk for any type of fracture increased significantly with lower BMI. Overall, the risk ratio (RR) per unit higher BMI was 0.98 (95% confidence interval [CI], 0.97-0.99) for any fracture, 0.97 (95% CI, 0.96-0.98) for osteoporotic fracture and 0.93 (95% CI, 0.91-0.94) for hip fracture (all p <0.001). The RR per unit change in BMI was very similar in men and women ( p >0.30). After adjusting for BMD, these RR became 1 for any fracture or osteoporotic fracture and 0.98 for hip fracture (significant in women). The gradient of fracture risk without adjustment for BMD was not linearly distributed across values for BMI. Instead, the contribution to fracture risk was much more marked at low values of BMI than at values above the median. This nonlinear relation of risk with BMI was most evident for hip fracture risk. When compared with a BMI of 25 kg/m(2), a BMI of 20 kg/m(2) was associated with a nearly twofold increase in risk ratio (RR=1.95; 95% CI, 1.71-2.22) for hip fracture. In contrast, a BMI of 30 kg/m(2), when compared with a BMI of 25 kg/m(2), was associated with only a 17% reduction in hip fracture risk (RR=0.83; 95% CI, 0.69-0.99). We conclude that low BMI confers a risk of substantial importance for all fractures that is largely independent of age and sex, but dependent on BMD. The significance of BMI as a risk factor varies according to the level of BMI. Its validation on an international basis permits the use of this risk factor in case-finding strategies.

The diagnostic accuracy of palpation and fine-needle biopsy and an evaluation of their combined use in the diagnosis of breast lesions: report on a prospective study in 1244 women with symptoms.

In 1244 women with breast symptoms an evaluation by means of palpation was made with respect to diagnosis of malignancy according to a four-grade scale ranging from "definite cancer" to "no cancer." Aspiration biopsy and cytologic examination were then performed in 984 breast lesions. The diagnosis from the cytologic evaluation ranged from benign, through three grades of atypia (slight, moderate, grave) to cancer. A histologic diagnosis was made in 411 cases and in 28% it was cancer. Cancer was found in 92.5% of the patients with a palpatory diagnosis of "definite cancer," and in 50% of those with a palpatory diagnosis of "strong suspicion of cancer." In all patients in whom cancer was diagnosed cytologically, the same diagnosis was made at histology, while 87.5% of those with grave atypia at the cytologic examination were diagnosed histologically as having cancer. A false negative cytologic diagnosis was made in 4% of the cancer cases. With a combination of palpation and cytology, 91% of the cancer cases fell within the groups "definite cancer," "strong suspicion of cancer" (palpation)/"cancer," "grave atypia" (cytology). No patients with cancer were evaluated as "no cancer" (palpation)/"no atypia" (cytology). In this group of 697 patients, however, one cancer was discovered after 7 months. The investigation showed that a thorough palpatory evaluation is a prerequisite for a good result of aspiration biopsy, in particular to meet the risk of a false negative cytologic diagnosis. The cytologic examination revealed cancer in 6 and 12 cases, respectively, when palpation gave no or some suspicion of cancer, and in many cases it was able to eliminate malignancy suspected on palpation. Cytologic atypia indicated cancer in a relatively high per cent, but was also noted in many cases found to be benign histologically. The possibilities of reducing the number of "unnecessary" surgical biopsies by using a combination of palpation and cytology is discussed.