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The intermediate filament nestin is upregulated in stem/progenitor cells and cancers, and regulates cell proliferation, migration, invasion and stemness. The present study comparatively analyzed serial autopsies of Japanese patients (n=2,206; males, 1,225; females, 981; median, 80.7 years old; range, 33–104 years old) with malignant tumors of whole organs, with respect to the clinical information, and 5 single nucleotide polymorphisms of the nestin gene. p.A1199P associated with pancreatic cancer (odds ratio, 4.4; 95% confidence interval, 1.9–10.0, P=0.001) while it did not associate with malignant neoplasms in other organs. p.A1199P did not associate with precancerous lesions of the pancreas. Single nucleotide polymorphisms of nestin were not associated with sex, drinking, smoking, or body weight. In conclusion, the amino acid 1,199 of nestin is localized in the tail structure of the filament and polymerizes with other intermediate filament proteins. The present results suggest that missense variations of nestin affect pancreatic carcinogenesis in Japanese patients. [ABSTRACT FROM AUTHOR]

Aim We aimed to study a single nucleotide polymorphism (SNP), rs2106261, in the transcription factor gene, ZFHX3 , in atrial fibrillation (AF) and other related phenotypes by phenome scanning in a Japanese population. Method We retrieved consecutive autopsy data ( n = 2433, mean age = 80 years) from the Japanese SNP database for geriatric diseases (JG-SNP). Clinical data, including an AF diagnosis, were collected from medical charts. Genotyping was performed with the DNA chip method. We also analyzed 42 pathological and 26 clinical phenotypes, including cerebral infarctions (CIs) and lung thromboembolisms (LTs), diagnosed by macroscopic inspection during the autopsy. Result Among the 2433 patients with available data, 18.6% had AF, 29.4% had CI, and 4.9% had LT phenotypes. The A allele of the rs2106261 SNP was significantly associated with AF, after adjusting for age, sex, diabetes, hypertension, and smoking (AA + AG/GG, OR = 1.51, 95%CI: 1.16–1.97, p = 0.002). In the entire cohort, CI was not associated with rs2106261 ( p = 0.14). However, among patients under 80 years old, rs2106261 was significantly associated with CI (AA + AG/GG, OR = 1.57, 95%CI: 1.09–2.26, p = 0.01). LT was also associated with rs2106261 (AA + AG/GG, OR = 1.99, 95%CI: 1.31–3.01, p = 0.001). Associations between rs2106261 and CI and LT remained positive after adjusting for the presence of AF, which indicated that this SNP variant might serve as an independent risk marker. Conclusion We showed that the ZFHX3 polymorphism, rs2106261 (A allele), was a risk marker for AF and AF-related phenotypes. The roles of this variant in the development of AF and its related phenotypes warrant further investigation. [ABSTRACT FROM AUTHOR]

• HOTAIR is a lncRNA involved in carcinogenesis. • Rs920778 has been implicated in susceptibility for cancers but with controversy. • We assessed the association of HOTAIR SNP rs920778 in consecutive autopsy samples. • Rs920778 does not contribute to cancer susceptibility in a Japanese population. The HOTAIR gene encodes a long noncoding RNA (lncRNA), which functions in development and tumorigenesis. A single nucleotide polymorphism (SNP) rs920778 in the HOTAIR gene, has been recurrently studied for susceptibility to many cancers including oesophageal cancer, gastric cancer, lung cancer, and hepatocellular carcinoma. Most of these studies were conducted in Chinese populations, and a few in Turkish, Iranian, and Portuguese populations. They mostly give rise to controversial results. It still remains largely unknown whether the cancer risk is conferred in a Japanese population. Here, we established an association study on the representative SNP rs920778, to examine its contribution to the presence of cancer in consecutive autopsy cases in the JG-SNP database. A total of 1373 subjects (mean age 80) including 827 cancer positive and 546 cancer negative subjects were analyzed. As a result, the occurrence of overall cancer was not associated with the rs920778 polymorphism (p > 0.05). For each cancer type, we did not find association except for lung cancer (p = 0.04) which was more likely a by-chance association after multiple testing. Our findings imply that rs920778 polymorphism does not affect total cancer presence and the effect on specific cancer types is also weak in the Japanese population. [ABSTRACT FROM AUTHOR]