A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Effect of continuous equal channel angular pressing on microstructure and properties of Al-Ti-C alloy

The Al-Ti-C alloy was extruded in multiple passes in a continuous manner by continuous equal channel angular pressing process. Through observation of the microstructure evolution, the mechanism of grain refinement and changes in mechanical properties were discussed.The results show that continuous equal channel angular pressing process can effectively refine the microstructure of Al-Ti-C alloy, and the grain size is reduced to about 1 μm.The deformation induction is the most important grain refinement mechanism in the deformation process.The accumulation of high density dislocations causes cracks at the interface between the Al matrix and TiAl3 and voids inside the TiAl3. The cracks further propagate through the entire TiAl3 particles, ultimately leading to the refinement of the second phase TiAl3 structure.At the same time, the pinning mechanism and shearing mechanism of the fine second phase TiAl3 structure promote the refinement of the Al matrix.After one pass of continuous equal channel angular pressing, the hardness of the alloy increases most obviously, which is 59.2% higher than that of the original state.With the increase of the number of extrusion passes, the increasing trend of hardness slows down, the plasticity of the alloy decreases, and toughness increases