Rachael Stolzenberg-Solomon, Laufey Amundadottir and colleagues report a genome-wide association study of pancreatic cancer. They identify four new susceptibility loci. We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74–0.84, P = 3.0 × 10−12), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30–1.65, P = 1.1 × 10−10), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10–1.20, P = 2.4 × 10−9) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12–1.25, P = 1.2 × 10−8). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76–0.85, P = 9.8 × 10−14). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10−7) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

Alison Klein and colleagues report a genome-wide meta-analysis to identify loci associated with pancreatic cancer risk. They identify associated variants at 17q25.1, 3q29, 7p13 and 2p13.3. Pancreatic cancer is the fourth leading cause of cancer death in the developed world1. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM3, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A7 and mismatch-repair genes8 and low-penetrance loci are associated with increased risk9,10,11,12. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19–1.34, P = 1.42 × 10−14), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84–0.92, P = 1.41 × 10−8) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85–0.93, P = 2.35 × 10−8). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09–1.19, P = 3.36 × 10−9), a region with previous suggestive evidence in Han Chinese12. We replicated previously reported associations at 9q34.2 (ABO)9, 13q22.1 (KLF5)10, 5p15.33 (TERT and CLPTM1)10,11, 13q12.2 (PDX1)11, 1q32.1 (NR5A2)10, 7q32.3 (LINC-PINT)11, 16q23.1 (BCAR1)11 and 22q12.1 (ZNRF3)11. Our study identifies new loci associated with pancreatic cancer risk.

Recent evidence indicate that small non-coding RNA molecules, called micro-RNAs (miRNAs), can bind to the 3′ untranslated regions (UTRs) of messenger RNAs and interfere with their translation, thereby regulating cell growth, differentiation, apoptosis and tumorigenesis. Genetic polymorphisms can reside on miRNA-binding sites. Thus, it is conceivable that the miRNA regulation may be affected by polymorphisms on the 3′ UTRs. Since gene deregulation is one of the key mechanisms by which cells can progress to cancer, we hypothesize that common polymorphisms within miRNA-target binding sites could play a role in the individual risk of cancer. In the present study, we selected the 3′ UTRs of 104 genes candidate for colorectal cancer (CRC) and we identified putative miRNA-binding sites by specialized algorithms (PicTar, DianaMicroT, miRBase, miRanda, TargetScan and microInspector). Fifty-seven single-nucleotide polymorphisms (SNPs) were identified in miRNA-binding sites. We evaluated the SNPs for their ability to affect the binding of the miRNA with its target, by assessing the variation of Gibbs free energy between the two alleles of each SNP. We found eight common polymorphisms that were further investigated by a case–control association studies. The study was carried out on a series of cases and controls from Czech Republic, a population with the highest worldwide incidence of CRC. We found statistically significant associations between risk of CRC and variant alleles of CD86 [odds ratio (OR) = 2.74; 95% confidence interval (CI) = 1.24–6.04, for the variant homozygotes] and INSR genes (OR = 1.94; 95% CI = 1.03–3.66, for the variant homozygotes). These results are the first reporting positive association between miRNA-binding SNPs sequences and cancer risk.

Objectives: We have undertaken a comprehensive study of common polymorphisms in genes of DNA repair, exploring both the risk of developing colorectal cancer and the prognosis of patients.