The prevalence of defective mismatch repair epithelial ovarian cancer in the Japanese hospital-based population was extremely low. Molecular mechanism involved in such defective mismatch repair ovarian cancers seems to be epigenetic events through MLH1 promotor hypermethylation or somatically mutated mismatch repair genes without germline mismatch repair mutation.

The present study confirmed the association between CDKN2A/B and CAD and identified a different associated risk allele of ADTRP. PDGFD was found to exhibit a gender-specific association with CAD. The combination of multiple risk alleles may be associated with a higher risk of CAD.

Cardiometabolic diseases are characterized as a combination of multiple risk factors for cardiovascular disease (CVD) and metabolic diseases including diabetes mellitus, dyslipidemia, hypertension and abdominal obesity. This cluster of abnormalities individually and interdependently leads to atherosclerosis and CVD morbidity and mortality. In the past decade, genome-wide association studies (GWASs) have identified a series of cardiometabolic disease-associated variants that can collectively explain a small proportion of the variability. Intriguingly, the susceptibility variants imputed from GWASs usually do not reside in the coding regions, suggesting a crucial role of the noncoding elements of the genome. In recent years, emerging evidence suggests that noncoding RNA (ncRNA) is functional for physiology and pathophysiology of human diseases. These include microRNAs and long noncoding RNAs (lncRNAs) that are now implicated in human diseases. The ncRNAs can interact with each other and with proteins, to interfere gene expressions, leading to the development of many human disorders. Although evidence suggests the functional role of lncRNAs in cardiometabolic traits, the molecular mechanisms of gene regulation underlying cardiometabolic diseases remain to be better defined. Here, we summarize the recent discoveries of lncRNA variations in the context of cardiometabolic diseases.

Polymerase proofreading-associated polyposis, caused by germline variants in the exonuclease domains of POLD1 and POLE, is a dominantly inherited rare condition characterized by oligo-adenomatous polyposis and increased risk of colorectal cancer, endometrial cancer and brain tumours. We report the first Japanese case of polymerase proofreading-associated polyposis carrying a POLD1 variant. The proband was a Japanese woman who had undergone resections of early colorectal carcinomas repeatedly and a hysterectomy with bilateral oophorectomy for endometrial cancer, all of which were diagnosed within 2 years after the first colectomy at 49 year old. Colonoscopic examinations demonstrated at least 14 non-cancerous polypoid lesions, some of which were histologically confirmed to be adenoma. Multigene panel sequencing identified a missense variant in POLD1 (c.1433G>A). Although her relatives did not undergo genetic testing, her father and paternal grandfather died of brain tumours at 53 and ~30 years of age, respectively.

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