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Competing interests The authors declare that they have no competing interests. Authors’ contributions XDC have made substantial contributions to conception, and drafting the manuscript. WGL have made substantial contributions to patients sample collection. FY carried out the molecular genetic studies. XYW carried out the protein expression detection and performed the statistical analysis. XX conceived of the study, and participated in its design, and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.”
“Background Type 2 diabetes (T2D) is associated with obesity. There is increasing evidence that T2D is associated with tumors [1] and cancers of the pancreas [2], prostate, breast, colon, endometrium, and liver [3]. T2D genes, such as HNF-1 beta and JAZF1, have been associated
with prostate SP600125 cost cancer [4–6]. Thus, T2D candidate genes may not only be obesity predisposing genes, but also tumor/cancer risk genes. CHOP mediates apoptosis PRKD3 and regulates mitochondrial gene expression, thus it may be implicated in beta cell inability to replicate as well as in insulin secretion defects. Following up on a linkage signal in the CHOP region of chromosome 12q13.1 in Italian T2D families, we have previously shown that CHOP 5′UTR-c.279T>C and +nt30C>T haplotype variants are associated with early-onset T2D under a recessive and additive model [7]. In addition, CHOP inhibits adipogenesis [8], thus CHOP gene variants may contribute to insulin resistance [9, 10] and/or obesity [11]. Since CHOP is regulating programmed cell death in response to stress stimuli [12], it is implicated in tumor/cancer development. CHOP is involved in the pathogenesis of myxoid liposarcoma, a rare human tumor in which a reciprocal chromosomal translocation creates a fusion protein consisting of CHOP and TLS, a potent oncoprotein [13]. Other tumor-specific fusion genes, such as EWS-CHOP and TLS/FUS-CHOP, have been detected in solid tumors [14] and liposarcomas [15–17]. Another rearrangement of the CHOP gene has been reported in myxoid liposarcoma [18]. Our aim was to find whether there is any association of the CHOP 5′UTR-c.