三重野 牧子

The predominant histological subtype of breast mucinous carcinoma in older women is type B (hypercellular type), and, in younger women, it is type A (hypocellular type). The characteristics of mucinous carcinomas of the same histological subtype may differ between older and younger women. This study aims to systematically clarify the pathological/immunohistochemical features of mucinous carcinomas. A total of 21 surgical cases of mucinous carcinoma (type A/B: 9/12 cases) in the older group (≥65 years) and 16 cases (type A/B: 14/2 cases) in the younger group (≤55 years) (n = 37) were included. Gross cystic disease fluid protein-15 (GCDFP-15) and eight other markers were used for immunostaining. The GCDFP-15-positive rate in the older group was high regardless of the histological subtype (type A, 77.8%; type B, 91.7%). The GCDFP-15 positivity in the older group was significantly higher than that in the younger group (p < 0.001 for Allred score). Among type A, GCDFP-15 positivity was significantly higher in the older group than in the younger group (p = 0.042 for the Allred score and p = 0.007 for the positivity rate). The present results suggest that GCDFP-15 expression characterizes mucinous carcinomas in older women.

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.

The transporter associated with antigen processing 2 (TAP2) gene is involved in the immunological response to tuberculosis (TB) infection. Variations in the TAP2 gene have been associated with TB infection in small population studies in India, Columbia, and Korea. We investigated the association of TAP2 polymorphisms with TB susceptibility in an elderly Japanese population. We analyzed samples from consecutive autopsy cases (n = 1850) registered in the Japanese Geriatric SNP Research database. TB was diagnosed pathologically by TB granuloma on autopsy samples. There were 289 cases and 1529 controls. Twenty-four single nucleotide variations (SNVs), including four missense variations in the TAP2 region, were genotyped using the Illumina Infinium Human Exome BeadChip array. Of the 24 SNVs in the TAP2 gene, rs4148871, rs4148876 (R651C), and rs2857103 showed statistically significant associations with TB susceptibility, and rs4148871 and rs2857103 also showed significant genotypic associations in a dominant allele model adjusted for age, sex, and smoking. Haplotype analysis showed that TAP2 allele *0103 conferred an increased TB risk (OR = 1.48, p = 0.0008), while the TAP2 *0201 allele was protective against TB (OR = 0.73, p = 0.0007). Our results suggest that TAP2 polymorphisms influence TB susceptibility in a Japanese population.

BACKGROUND: Many genetic and environmental factors are involved in the etiology of nicotine dependence. Although several candidate gene variations have been reported by candidate gene studies or genome-wide association studies (GWASs) to be associated with smoking behavior and the vulnerability to nicotine dependence, such studies have been mostly conducted with subjects with European ancestry. However, genetic factors have rarely been investigated for the Japanese population as GWASs. To elucidate genetic factors involved in nicotine dependence in Japanese, the present study comprehensively explored genetic contributors to nicotine dependence by using whole-genome genotyping arrays with more than 200,000 markers in Japanese subjects. RESULTS: The subjects for the GWAS and replication study were 148 and 374 patients, respectively. A two-stage GWAS was conducted using the Fagerström Test for Nicotine Dependence (FTND), Tobacco Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as indices of nicotine dependence. For the additional association analyses, patients who underwent major abdominal surgery, patients with methamphetamine dependence/psychosis, and healthy subjects with schizotypal personality trait data were recruited. Autopsy specimens with various diseases were also evaluated. After the study of associations between more than 200,000 marker single-nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with FTND, with a p value of 0.0005921 in the two-stage GWAS. This possible association was replicated for the remaining 374 samples. This SNP was also associated with postoperative pain, the initiation of methamphetamine use, schizotypal personality traits, and susceptibility to goiter. CONCLUSIONS: Although the p value did not reach a conventional genome-wide level of significance in our two-stage GWAS, we obtained significant results in the subsequent analyses that suggest that the rs2653349 SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence and possibly pain, schizotypal personality traits, and goiter in the Japanese population.

&lt;b&gt;目的&lt;/b&gt; 国民生活基礎調査の世帯数と患者調査の推計患者数について，東日本大震災によって調査対象から除外された地域の補完を行った。&lt;br/&gt;&lt;b&gt;方法&lt;/b&gt; 国民生活基礎調査において，東日本大震災によって調査対象から除外された2011年の岩手県・宮城県・福島県と2012年の福島県の世帯数について，前後の大規模調査年の情報を用いて線型内挿法で補完した。2011年における宮城県と福島県の推計患者数について，同年の患者調査（宮城県の石巻・気仙沼医療圏と福島県が調査対象から除外）と2012年の福島県患者調査，2011年と2012年の医療施設調査と病院報告を用いて補完した。&lt;br/&gt;&lt;b&gt;結果&lt;/b&gt; 全国の世帯数（各年 6 月時点）における補完値は2011年で48,732千世帯，2012年で48,874千世帯であった。世帯構造別の世帯数において，2011年と2012年の調査値が前後の年次

&lt;b&gt;目的&lt;/b&gt; 国民生活基礎調査の世帯数と患者調査の推計患者数について，東日本大震災によって調査対象から除外された地域の補完を行った。&lt;br/&gt;&lt;b&gt;方法&lt;/b&gt; 国民生活基礎調査において，東日本大震災によって調査対象から除外された2011年の岩手県・宮城県・福島県と2012年の福島県の世帯数について，前後の大規模調査年の情報を用いて線型内挿法で補完した。2011年における宮城県と福島県の推計患者数について，同年の患者調査（宮城県の石巻・気仙沼医療圏と福島県が調査対象から除外）と2012年の福島県患者調査，2011年と2012年の医療施設調査と病院報告を用いて補完した。&lt;br/&gt;&lt;b&gt;結果&lt;/b&gt; 全国の世帯数（各年 6 月時点）における補完値は2011年で48,732千世帯，2012年で48,874千世帯であった。世帯構造別の世帯数において，2011年と2012年の調査値が前後の年次

&lt;b&gt;目的&lt;/b&gt; 国民生活基礎調査の世帯数と患者調査の推計患者数について，東日本大震災によって調査対象から除外された地域の補完を行った。&lt;br/&gt;&lt;b&gt;方法&lt;/b&gt; 国民生活基礎調査において，東日本大震災によって調査対象から除外された2011年の岩手県・宮城県・福島県と2012年の福島県の世帯数について，前後の大規模調査年の情報を用いて線型内挿法で補完した。2011年における宮城県と福島県の推計患者数について，同年の患者調査（宮城県の石巻・気仙沼医療圏と福島県が調査対象から除外）と2012年の福島県患者調査，2011年と2012年の医療施設調査と病院報告を用いて補完した。&lt;br/&gt;&lt;b&gt;結果&lt;/b&gt; 全国の世帯数（各年 6 月時点）における補完値は2011年で48,732千世帯，2012年で48,874千世帯であった。世帯構造別の世帯数において，2011年と2012年の調査値が前後の年次