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A letter to the editor is presented in response to the article "Prognostic Value of 25-hydroxyvitamin D3 Levels at Diagnosis and During Follow-up in Melanoma Patients."

It was suggested that vitamin D levels influence cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. Results from previous studies on the association of VDR polymorphisms with different cancer types are somewhat contradictory, and the role of VDR in the etiology of cancer is still equivocal. We therefore performed a meta-analysis on the association between the two most studied VDR polymorphisms (FokI and BsmI) and any cancer site. Up to January 2009, we identified 67 independent studies. We used random-effects models to provide summary odds ratio (SOR) for VDR polymorphisms and cancer. We tested homogeneity of effects across studies and publication bias and explored between-study heterogeneity. When comparing FokI ff with FF carriers, we found a significant increase in skin cancer [SOR; 95% confidence intervals (CIs): 1.30; 1.04–1.61] and breast cancer (SOR; 95%CI: 1.14; 1.03–1.27) risk. For the same genotype comparison, we found a significantly higher risk of cancer when we pooled estimates from cancer sites possibly associated with vitamin D levels (prostate, breast, skin, ovary, non-Hodgkin lymphoma and colorectal). A significant reduction in prostate cancer risk was observed for carriers of BsmI Bb compared with bb genotype (SOR; 95%CI: 0.83; 0.69–0.99). In Caucasian populations, both Bb and BB carriers had a significant reduced risk of cancer at any site. In conclusion, this meta-analysis showed that VDR FokI and BsmI polymorphisms might modulate the risk of cancer of breast, skin and prostate and possibly affect cancer risk at any site in Caucasians. [ABSTRACT FROM AUTHOR]

Objective: Although breast cancer screening can benefit from Artificial Intelligence (AI), it is still unknown whether, to which extent or under which conditions, the use of AI is going to be accepted by the general population. The aim of our study is to evaluate what the females who are eligible for breast cancer screening know about AI and how they perceive such innovation. Methods: We used a prospective survey consisting of a 11‐multiple‐choice questionnaire evaluating statistical associations with Chi‐Square‐test or Fisher‐exact‐test. Multinomial‐logistic‐regression was performed on items with more than two response categories. Odds ratio (OR) with 95% CI were computed to estimate the probability of a specific response according to patient's characteristics. Results: In the 800 analysed questionnaires, 51% of respondents confirmed to have knowledge of AI. Of these, 88% expressed a positive opinion about its use in medicine. Non‐Italian respondents were associated with the belief of having a deep awareness about AI more often than Italian respondents (OR = 1.91;95% CI[1.10–3.33]). Higher education level was associated with better opinions on the use of AI in medicine (OR = 4.69;95% CI[1.36–16.12]). According to 94% of respondents, the radiologists should always produce their own report on mammograms, whilst 77% agreed that AI should be used as a second reader. Most respondents (52%) considered that both the software developer and the radiologist should be held accountable for AI errors. Conclusions: Most of the females undergoing screening in our Institute approve the introduction of AI, although only as a support to radiologist, and not in substitution thereof. Yet, accountability in case of AI errors is still unsolved. advances in knowledge: This survey may be considered as a pilot‐study for the development of large‐scale studies to understand females's demands and concerns about AI applications in breast cancer screening. [ABSTRACT FROM AUTHOR]

We have updated our previous meta-analysis published in Carcinogenesis to explore the role of FokI polymorphism of vitamin D receptor (VDR) gene and all cancer sites. Numerous studies investigated the associations of FokI with various types of cancer.Numerous studies investigated the associations of VDR polymorphisms with various types of cancer, suggesting an influence on cancer risk. FokI is one of the most frequently analysed polymorphisms but the results from single studies are contradictory. We performed a meta-analysis looking at the association between the FokI and all cancer sites and investigating sources of heterogeneity. We identified 77 independent studies up to April 2014. We presented the summary odds ratios (SORs) by cancer sites, ethnicity and study features. We found a significant association between FokI and ovarian cancer for ff genotype versus FF with no heterogeneity: SOR = 1.20 (95% CI: 1.02–1.41, I2 = 0%). Moreover, we found a significant increased risk of any cancer: SOR = 1.08 (95% CI: 1.01–1.16, I2 = 58%). A significant increased risk of any cancer is confirmed among Caucasian, among studies in Hardy–Weinberg equilibrium and nested case–control studies. Furthermore, among studies in Hardy–Weinberg equilibrium, skin cancer was found significantly associated with FokI: SOR = 1.24 (95% CI: 1.01–1.54; I2 = 24%) for ff versus FF. The estimated number of cases attributable to ff genotype is 4221 for ovarian cancer and 52858 for skin cancer worldwide each year. No indication for publication bias was found for any cancer site. In conclusion, we found an overall significant association of FokI polymorphism with any cancer, with differential effect by ethnicity. In particular, the summary estimates indicate an increase risk for ovarian and skin cancer for ff versus FF. However, other factors may act modifying the association, and further studies are needed to clarify the impact on cancer risk. [ABSTRACT FROM AUTHOR]

Beta-2 microglobulin (β2m) is the light chain of Class I major histocompatibility complex (MHC-I) complex. β2m is an intrinsically amyloidogenic protein capable of forming amyloid fibrils in vitro and in vivo. β2m displays the typical immunoglobulin-like fold with a disulphide bridge (Cys25–Cys80) cross-linking the two β-sheets. Engineering of the loop comprised between β-strands D and E has shown that mutations in this region affect protein structure, fold stability, folding kinetics and amyloid aggregation properties. Such overall effects have been related to the DE loop backbone structure, which presents a strained conformation in the wild-type (wt) protein, and a type I β-turn in the W60G mutant. Here, we report a biophysical and structural characterization of the K58P-W60G β2m mutant, where a Pro residue has been introduced in the type I β-turn i + 1 position. The K58P-W60G mutant shows improved chemical and temperature stability and faster folding relative to wt β2m. The crystal structure (1.25 Å resolution) shows that the Cys25–Cys80 disulphide bridge is unexpectedly severed, in agreement with electrospray ionization–mass spectrometry (ESI–MS) spectra that indicate that a fraction of the purified protein lacks the internal disulphide bond. These observations suggest a stabilizing role for Pro58, and stress a crucial role for the DE loop in determining β2m biophysical properties. [ABSTRACT FROM PUBLISHER]