Study profile on baseline survey of Daiko Study in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study).

The Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) is a long-term cohort study to investigate the interactions among genotypes, lifestyles, and lifestyle-related diseases, especially cancer. This article reports the outline of the baseline survey of the Daiko Study, one site of the J-MICC Study. That survey was conducted between June 9, 2008 and May 31, 2010 at the Daiko Medical Center of Nagoya University in Nagoya, Japan. Subjects were registered residents of Nagoya City aged 35 to 69 years who had not participated in other J-MICC sites. Recruitment was mainly announced through leaflets distributed in mailboxes citywide, personal communications, and regional information, such as posters in public or commercial facilities. Participants provided blood plasma, serum, buffy coat, urine, and data on health check-ups. They also completed a self-reported questionnaire on lifestyle, disease history, family history, and for women, reproductive history. As of the end of September 2010, 4 out of 5172 registered participants had withdrawn from the study, leaving data from 5168 participants (1467 males and 3701 females) available for analysis. Mean age +/- standard deviation (SD) was 52.5 +/- 10.3 years. Current smokers accounted for 24.1% (n=354) of males and 6.9% (n=256) of females. Current drinkers included 74.9% (n=1099) of males and 45.9% (n=1699) of females. Lifestyle data and specimens were successfully collected to examine any associations among disease biomarkers, lifestyles, and genotypes.

Correlation of pathological grade and tumor stage of urothelial carcinomas with CD109 expression.

Bladder cancer is one of the most common malignant diseases. Since a high-rate of recurrence is a serious problem for early stage urothelial carcinomas, new strategies for the management of recurrent urothelial carcinomas have been explored. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein and is expressed in various cancer tissues, mainly squamous cell carcinomas. CD109 negatively controls transforming growth factor (TGF)-ß/Smad signaling in vitro. In this study, we analyzed the clinical significance of CD109 expression in bladder cancer using immunohistochemistry. Of 156 urothelial carcinoma tissues, 69.9% were positive for CD109, whereas CD109 was not expressed in seven normal bladder epithelia. CD109 expression was significantly higher in non-muscle-invasive (pTa+pT1) or low-grade (G1+G2) tumors than in muscle-invasive (pT2-4) or high-grade (G3) tumors, and was associated with cancer-specific survival. Simultaneous immunostaining of CD109 and phosphorylated Smad2 showed an inverse immunoreactivity relationship between the two, suggesting that CD109 inhibits TGF-ß/Smad signaling in tumor tissues. Interestingly, CD109 was found to be highly expressed in the basal layer of non-invasive urothelial carcinomas, and the expression pattern was similar to that of CD44, a marker of cancer stem cells. These findings suggest that CD109 is involved in bladder tumorigenesis and is a potential target for cancer immunotherapy.

Association of calcium urolithiasis with urokinase P141L and 3'-UTR C>T polymorphisms in a Japanese population.

This was a case-control study to analyze the associations between calcium urolithiasis and the urokinase polymorphisms, P141L (rs2227564) and 3'-UTR C>T (rs4065), in a Japanese population. Cases consisted of 232 patients with urinary calcium stones (174 men and 58 women) who presented to a general hospital between April 2009 and June 2011. Among these cases, 115 (49.6 %) patients had calcium oxalate stones alone, and 113 (48.7 %) patients had calcium oxalate stones mixed with calcium phosphate stones. Controls consisted of 454 subjects who had a routine health check-up in the same prefecture. The two polymorphisms were genotyped via polymerase chain reaction with confronting two-pair primers. In the control group, the genotype frequencies of P141L were 0.573 for PP, 0.375 for PL, and 0.052 for LL, and those of 3'-UTR C>T were 0.835 for CC, 0.165 for CT, and TT was not identified. Neither of the polymorphisms was significantly associated with urolithiasis. The age- and sex-adjusted odds ratios of urolithiasis were 0.96 [95 % confidence interval (CI), 0.66-1.41] for PL and 1.22 (0.58-2.57) for LL as compared with PP genotype of P141L, and 1.01 (0.62-1.64) for CT as compared with CC genotype of 3'-UTR C>T. When compared with the PP genotype of P141L, the frequency of PL was significantly lower in female cases with a family history of urolithiasis than in females without such family history (p = 0.028). P141L and 3'-UTR polymorphisms of the urokinase gene are not associated with urolithiasis in a Japanese population.

A C to T polymorphism of urokinase plasminogen activator (P141L) is associated with Helicobacter pylori infection.

Urokinase plasminogen activator (uPA) plays an important role in tumor invasion and certain inflammatory diseases. However, few studies have paid attention to how the uPA is associated with Helicobacter pylori infection and gastric atrophy. This study investigated associations of a C-to-T polymorphism of uPA (P141L, rs2227564) in exon 6 in 454 Japanese health checkup examinees (126 males and 328 females) aged 35 to 85 without a history of cancer. The uPA was genotyped by polymerase chain reaction with two-pair primers. The genotype distribution was in Hardy-Weinberg equilibrium (p=0.52) and the frequency of the T allele was 0.239. The risk of H. pylori sero-positivity was significantly reduced with the T/T genotype; the odds ratio (OR) relative to the C/C genotype was 0.34 (95% confidence interval [CI]: 0.14 to 0.86). Of the sero-negative subjects, 21 with atrophy were infected with H. pylori but lost their sero-positivity. After reclassifying them together with the sero-positive subjects, the corresponding OR was 0.40 (95% CI: 0.16 to 1.00), confirming that the T/T genotype decreased the risk of H. pylori infection. This gene polymorphism was not associated with the risk of gastric atrophy. In conclusion, this study indicated a possibility that the uPA minor homozygous genotype was associated with a reduction of H. pylori infection risk. Further studies are required to confirm these findings.