Pancreatic acinar cell carcinoma (ACC) is an aggressive exocrine tumor with largely unknown biology. Here, to identify potential targets for personalized treatment, we perform integrative genome-wide and epigenome-wide analyses. The results show frequently aberrant DNA methylation, abundant chromosomal amplifications and deletions, and mutational signatures suggesting defective DNA repair. In contrast to pancreatic ductal adenocarcinoma, no recurrent point mutations are detected. The tumor suppressors ID3, ARID1A, APC, and CDKN2A are frequently impaired also on the protein level and thus potentially affect ACC tumorigenesis. Consequently, this work identifies promising therapeutic targets in ACC for drugs recently approved for precision cancer therapy.

Advanced glycation end products (AGEs) accumulate in tissues with aging and may influence age-related diseases. They can be estimated non-invasively by skin autofluorescence (SAF) using the AGE Reader™. Serum 25-hydroxyvitamin D3 (25(OH)D3) may inhibit AGEs accumulation through anti-oxidative and anti-inflammatory properties but evidence in humans is scarce. The objective was to investigate the association between serum 25(OH)D3 and SAF in the population-based cohort study. Serum 25(OH)D3 and other covariates were measured at baseline. SAF was measured on average 11.5 years later. Known risk factors for AGE accumulation such as higher age, BMI, and coffee intake, male sex, smoking, diabetes, and decreased renal function were measured at baseline. Linear regression models were adopted to explore the association between 25(OH)D3 and SAF with adjustment for confounders. Interaction terms were tested to identify effect modification. The study was conducted in the general community. 2746 community-dwelling participants (age ≥ 45 years) from the Rotterdam Study were included. Serum 25(OH)D3 inversely associated with SAF and explained 1.5% of the variance (unstandardized B = − 0.002 (95% CI[− 0.003, − 0.002]), standardized β = − 0.125), independently of known risk factors and medication intake. The association was present in both diabetics (B = − 0.004 (95% CI[− 0.008, − 0.001]), β = − 0.192) and non-diabetics (B = − 0.002 (95% CI[− 0.003, − 0.002]), β = − 0.122), both sexes, both smokers and non-smokers and in each RS subcohort. Serum 25(OH)D3 concentration was significantly and inversely associated with SAF measured prospectively, also after adjustment for known risk factors for high SAF and the number of medication used, but the causal chain is yet to be explored in future studies.Clinical Trial Registry (1) Netherlands National Trial Register: Trial ID: NTR6831 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831). (2) WHO International Clinical Trials Registry Platform: under shared catalogue number NTR6831 (www.who.int/ictrp/network/primary/en/).Electronic supplementary materialThe online version of this article (10.1007/s10654-018-0444-2) contains supplementary material, which is available to authorized users.