Transporter Associated With Antigen Processing (TAP) 1 Gene Polymorphisms and Risks of Urothelial Cell Carcinoma Among the Japanese Population.

Urothelial cell carcinoma is one of the costliest types of cancer because of its recurrence, lengthy course of therapy, and tendency to lead to further complications. Gene polymorphisms are one of many factors that are thought to cause the carcinogenesis of urothelial cell carcinoma. Two single-nucleotide polymorphisms (SNPs) of the transporter associated with antigen processing (TAP) 1 gene and their relationship with the risks of urothelial cell carcinoma in the Japanese population were examined in this study by using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) for genotyping and statistical analysis. The adjusted odd ratios with 95% confidence interval (CI) of the mutant types (A/G+G/G) in females for the I333V and D637G polymorphisms are 2.28 (1.11-4.66) and 2.50 (1.21-5.17), respectively. The findings showed that females with the (A/G+G/G) genotype are more likely to develop urothelial cell carcinoma than those with the A/A genotype. Any correlation between smoking and gene polymorphism was absent. Results indicate that TAP1 gene polymorphisms and the risk of urothelial cell carcinoma are related in females.

Epidemiological Study of Metastatic Brain Tumors in Miyazaki Prefecture: A Regional 10-year Survey in Southern Japan.

Advances in cancer treatment have improved the survival of patients with cancer, with a concomitant increase in the proportion of patients with metastatic brain tumors (MBTs). In this study, we used cancer registries established in Japan after 2016 and available patient data by organ in order to conduct an accurate epidemiological study. To the best of our knowledge, this is the first study to report on the detailed epidemiological data on MBT at the prefectural level in Japan using the Miyazaki Brain Tumor Database and Miyazaki Cancer Registry. This study included 425 new cases of MBTs diagnosed in Miyazaki Prefecture from 2007 to 2016. As per our findings, the most frequent primary tumor in Miyazaki Prefecture was found to be in the lung (49.4%), followed by colon/rectum/anus (9.4%) and breast (8.5%). Among patients with MBTs, 59.1% were males, a number closely similar to that of Japan, as shown in the Japanese Brain Tumor Registry (55.5%). The median age at diagnosis was 68 and 63 years in Miyazaki Prefecture and Japan, respectively. Although more patients were symptomatic in Miyazaki Prefecture than in Japan (88.5% vs. 15.5%), fewer patients opted for surgery (33.6% vs. 61.9%), probably because of their advanced age at diagnosis. As per the findings of this study, the annual incidence rate of new MBTs (i.e., ratio of the number of new cancer registrations to that of new MBT patients in Miyazaki Prefecture) was at 0.41%. The number of tumor sites in MBTs was independent of the total number of cancers per organ. Considering the expansion of cancer registries worldwide, including those on brain tumors, further epidemiological analysis of MBTs is deemed warranted.

The Relationship Between CTLA-4 (-318 C/T) Polymorphism and Urothelial Cancer Carcinogenesis in Japanese Patients.

Background Urothelial cancer is one of the most common types of urinary system cancer and there are several factors that can influence its growth. One of the most prominent factors among these is genetics. The Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) gene is suspected to be a susceptibility gene in urothelial carcinoma. The aim of this study is to investigate polymorphism in the CTLA-4 gene (CTLA-4 -318 C/T) and whether it is associated with urothelial cancer. Methods The study population consisted of 253 cases and 272 controls. In this case-control study, DNA was extracted from peripheral blood cells, and the CTLA-4 -318C/T genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism. Results C/T (adjusted OR (aOR) 3.37; 95%CI: 1.98-5.74) genotype, C/T + T/T (aOR 3.25; 95%CI: 1.96-5.39) genotype, and T allele (aOR 2.94 95%CI: 1.87-4.62) all indicated they are significant risk factors for urothelial cancer, with the effects of polymorphism being higher in the nonsmoker group than in the smoker group. Furthermore, the association between polymorphism and urothelial cancer carcinogenesis was similar among men and women. Conclusions This is the first study examining the association between CTLA-4 -318C/T polymorphism and urothelial carcinoma in Japanese patients. A significant association between CTLA-4 -318C/T polymorphism and urothelial cancer among Japanese patients was detected in this study. This supports the development of research on polymorphisms in urothelial cancer and is an important root of immunoreactions in cancer. We believe this study will be beneficial to clarify the relationship between CTLA-4 polymorphism and urothelial cancer.

The Relationship Between PD-1(rs2227981) and PD-L1(rs2890658) Polymorphisms and Urothelial Cell Carcinoma.

Background Urothelial cell carcinoma, which is believed to develop from the urothelium (transitional epithelium), is the most common aggressive tumor and accounts for the ten most prevalent cancers in the world. The risk factors for urothelial cell carcinoma are aging, smoking, gender, and genetic alternations. Programmed cell death1 (PD-1) has been widely described as a negative regulator of T-cells by sending inhibitory signals to the T-cell. Through PD-1 binding with PD-L1 (ligand for PD-1), an inhibitory signal is propagated to the T cell. The polymorphisms of PD-1 and PD-L1 lead to an efficient T-cell response and affect an anti-tumor reaction. The polymorphisms of PD-1 and PD-L1 could also affect the carcinogenesis of human cancer, including urothelial cell carcinoma. Therefore, in this study, we evaluated the relation between PD-1(rs2227981) and PD-L1(rs2890658) polymorphisms and the carcinogenesis of urothelial cell carcinoma. Materials and methods This study was conducted using 211 healthy controls and 256 cases of urothelial cell carcinoma among the Japanese population. The DNA samples were extracted from the peripheral white blood cells of each subject. The genotype was detected by using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results C/T (Adjusted OR 1.55, 95% CI:1.02-2.35) and C/T+T/T (OR 1.46, 95% CI:1.01-2.12) genotypes of PD-1 rs2227981 were significant and risk factors for urothelial cancer. Male with A/A genotype in PD-L1 and CT genotype in PD-1 has a significant higher risk factor compared with other genotypes (Adjusted OR 1.83, 95% CI:1.05-3.21). Conclusions and discussion We found that C/T(PD-1) and "A/A (PD-L1) and C/T(PD-1)" were predominant in urothelial cell carcinoma cases. This indicates that C/T(PD-1) and "A/A (PD-L1) and C/T(PD-1)" genotypes could increase susceptibility to urothelial cell carcinoma. However, since our findings indicated that the effects of PD-1 and PD-L1 polymorphisms included discrepancies, additional research will be needed to evaluate the relationship between human cancer and PD-1 and PD-L1 polymorphisms. This is the first study that seeks to find the relation between PD-1(rs2227981) and PD-L1(rs2890658) polymorphisms concerning urothelial cell carcinoma among the Japanese population.

PER3 polymorphisms and their association with prostate cancer risk in Japanese men.

INTRODUCTION: Prostate cancer (PCa) is one of the most common cancers affecting men globally. Although PER3 has been suggested as a risk factor for cancer development, there are few reports elucidating the relationship between PER3 and PCa. We investigated the association between PER3 polymorphisms (rs2640908 and VNTR) and susceptibility to PCa in the Japanese population. METHODS: Eighty three patients with PCa and 122 controls participated in this study. We analyzed rs2640908 and VNTR polymorphisms by using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: Compared to the C/C genotype with the rs2640908 polymorphism, the T/T (OR: 0.35, 95% CI: 0.15-0.81, P = 0.02) and C/T + T/T (OR: 0.46, 95% CI: 0.24-0.88, P = 0.02) genotypes had a significantly lower risk of PCa. TT (OR: 0.29, 95% CI: 0.10-0.77, P = 0.02) and CT + TT (OR: 0.47, 95% CI: 0.23-0.97, P = 0.04) also had significant protection against PCa in the smoker group. Significantly, we observed an association between smoking and rs2640908 polymorphism in this study. However, no association between the VNTR polymorphisms and PCa was detected. CONCLUSIONS: Our results suggest that PER3 rs2640908 polymorphisms influence an individual's susceptibility to PCa.

PER1 rs3027188 Polymorphism and its Association with the Risk of Colorectal Cancer in the Japanese Population.

Colorectal cancer(CRC)accounted for the largest number of new cases of cancer in 2018. CRC is caused by a multifactorial disease process including disruption of the circadian rhythm. Period 1(PER1),as one of the circadian genes,has a role in the cell cycle as well as influence on the cancer process. In this research,we investigate the association of PER1(rs3027188) polymorphism and susceptibility to CRC in conjunction with gender and smoking status. This research was a case-control study in the Japanese population which included 121 CRC patients and 197 noncancerous clinical controls. Genomic deoxyribonucleic acid(DNA)was extracted from peripheral blood lymphocytes. The analysis to detect single-nucleotide polymorphisms( SNPs)in PER1(rs3027188)used polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Overall,there was no significant association between PER1(rs3027188)and CRC. When stratified by gender and smoking status,the results indicated that,compared with the C/C genotype,the G/G genotype among females was significantly less common in the cancer cases than in the controls(adjusted ORs: 0.19[95%CI: 0.04-0.95]). A significant association was found between the G allele of PER1(rs3027188)and reduced risk of CRC in females,while smoking had no association with PER1(rs3027188)in CRC.

The correlation between PER3 rs2640908 polymorphism and colorectal Cancer in the Japanese population

Background: Colorectal cancer (CRC) is one of the most common cancers in Japan. Many factors influence this cancer, one of which is circadian rhythm disruption. Our research investigated the correlation between singlenucleotide polymorphisms (SNPs) in the Period 3 (PER3) (rs2640908), which is one of the circadian genes, and colorectal cancer in the Japanese population. Methods: The study participants consisted of 121 cases and 197 controls. DNA was extracted from participants' peripheral blood cells, and polymerase chain reaction­restriction fragment length polymorphism analysis (PCRRFLP) was performed to detect genotypes of PER3. Results: Participants with T/T genotype were at lower risk of developing colorectal cancer than participants with C/C genotype (adjusted ORs = 0.32 (95% CI: 0.15­0.63)). When stratified by gender and smoking status, T/T genotype were associated with a decreased susceptibility to cancer in males only (adjusted ORs: 0.23 (95% CI: 0.09­0.59)), T/T genotype were also associated with a decreased susceptibility to cancer among both smokers and non-smokers. Conclusions: A significant association was found between the T allele of PER3 polymorphism and a reduced risk of colorectal cancer, especially in males. Smoking status showed no association with the relationship between PER3 genotype and CRC carcinogenesis (AU)

Media exposure, interactive health literacy, and adolescents' susceptibility to future smoking.

BACKGROUND: Few studies have investigated interactive health literacy (IHL)'s relationship with adolescents' smoking-related behavior. This study investigated IHL's association with adolescents' susceptibility to future smoking. MATERIALS AND METHODS: We conducted a school-based cross-sectional study of Japanese students enrolled in public junior high school, grades 7-9 (n=1937), who completed a self-report questionnaire. Variables were grade, gender, media exposure [television (TV), internet, and magazines], IHL (interest in learning about health, understanding what they hear about health, trying to follow what is taught about health), and susceptibility to future smoking. RESULTS: Significant findings were: [1] media exposure was positively associated with adolescents' susceptibility to future smoking (TV: p<0.01, internet: p<0.01, magazines: p<0.01); [2] IHL was negatively associated with adolescents' susceptibility to future smoking (interest in learning about health: p<0.001; understanding what they hear about health: p<0.05; trying to follow what is taught about health: p<0.001). IHL's influence on susceptibility to future smoking was found to be marginally stronger than that of media exposure. CONCLUSION: School health-education programs that promote adolescents' IHL may effectively reduce adolescents' susceptibility to future smoking.

XPC intron11 C/A polymorphism as a risk factor for prostate cancer.

OBJECTIVES: DNA repair genes play an important role in protection against environmental and endogenous DNA damage, and constitute the first line of defense against cancer. Xeroderma pigmentosum complementation group C (XPC) is involved in the damage recognition step during nucleotide excision repair. The relationship between XPC intron11 C/A polymorphism and cancer risk has not been widely studied. Hence, this study evaluated the relationship between the XPC intron11 C/A polymorphism and prostate cancer risk. MATERIALS AND METHODS: This hospital-based cohort consisted of 152 patients with prostate cancer and 142 male controls. The XPC intron11 C/A genotype was determined using the PCR-RFLP method. Medical, occupational, and cigarette-smoking history was obtained from each participant using questionnaires. RESULTS: Logistic regression analysis revealed that compared to controls, the frequencies of the A/A and C/A genotypes were significantly higher than those of the C/C genotype in cancer patients (OR = 2.03, 95% confidence interval (CI) 1.03-3.98 and OR = 1.91, 95% CI 1.13-3.24, respectively). We also found that the frequency of the A/A genotype was significantly higher in cancer cases than in controls among non-smokers (OR = 7.7, 95% CI 1.38-42.88, compared to the C/C genotype). CONCLUSION: We found that the XPC intron11 C/A polymorphism was associated with an increased risk of prostate cancer. Among non-smokers, the A/A genotype was significantly more prevalent in prostate cancer patients than in controls.

The genotype of the transporter associated with antigen processing gene affects susceptibility to colorectal cancer in Japanese.

OBJECTIVE: Although colorectal cancer (CRC) is one of the most frequent malignancies in Japan, the associated genetic factors remain to be elucidated. Functional loss of the transporter associated with antigen processing (TAP) 1 gene induces carcinogenesis. We investigated whether single nucleotide polymorphisms (SNPs) in the TAP1 gene (rs735883) are associated with susceptibility to CRC in a Japanese population. METHODS: The study participants were 143 cases and 243 clinical controls. After extracting DNA from their peripheral blood cells, genotyping was conducted by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Participants with a mutated allele had an increased risk for CRC. The adjusted odds ratios for the C/T, T/T, and the mutation type (C/T + T/T) compared to that of wild type (C/C) were 2.27 [95 % confidence interval (CI), 1.43-3.67], 1.95 (95 % CI, 0.88-4.30), and 2.22 (95 % CI, 1.42-3.55), respectively. Furthermore, a significant trend in the rate of cases was observed with an increasing number of mutated alleles (P for trend = 0.0068). CONCLUSIONS: The genotype of the TAP1 gene is associated with susceptibility to CRC.

Increased plasma caveolin-1 levels are associated with progression of prostate cancer among Japanese men.

AIM: Up-regulation of caveolin-1 (CAV1) is associated with aggressive prostate cancer. Among Caucasian and African-American patients, plasma CAV1 levels are elevated in patients with castration-resistant prostate cancer (CRPC), but not in those with hormone-sensitive prostate cancer (non-CRPC), which implies that CAV1 could be a therapeutic target for CRPC. Here, we evaluated associations between plasma CAV1 levels and these types of cancer in Japanese men, and CAV1 expression in PC3 (CRPC) and LNCaP (non-CRPC) cell lines. MATERIALS AND METHODS: Plasma samples were obtained from 58 patients with prostate cancer: 36 with CRPC and 22 with non-CRPC. Enzyme-linked immuno sorbent assay (ELISA) kits were used to determine CAV1 plasma levels; qRT-PCR and western blots were used to evaluate the expression of CAV1 mRNA and protein in cell lines. RESULTS: Plasma CAV1 levels in patients with CRPC were greatly higher than in those with non-CRPC (1.46±1.37 ng/ml in CRPC; 0.56±0.32 ng/ml in non-CRPC, p<0.004). Western blot and real-time qRT-PCR showed CAV1 protein and mRNA in PC3 cells to be significantly overexpressed compared to its expression in LNCaP cells (p<0.0001). CONCLUSION: Our results showed a relationship between CAV1 expression and prostate cancer progression, and support the possibility of CAV1 as a therapeutic target for CRPC.

Functional polymorphism in the CAV1 T29107A gene and its association with prostate cancer risk among Japanese men.

AIM: To evaluate the relationship between the Caveolin-1 (CAV1) T29107A (rs7804372) polymorphism and the risk of prostate cancer among Japanese populations, and the associations between CAV1 polymorphisms and clinicopathological characteristics, including Gleason grade and prostate-specific antigen (PSA) grade. MATERIALS AND METHODS: We recruited 134 patients with prostate cancer and 86 healthy controls matched for age and smoking status. The CAV1 T29107A polymorphism status was determined by polymerase chain reaction and restriction fragment-length polymorphism analysis. RESULTS: Genotype distributions (p=0.0045) and allelic frequencies (p=0.0018) differed between prostate cancer and control groups in terms of the CAV1 T29107A polymorphism (Pearson's χ(2) test). Logistic regression analysis of case and control outcomes showed an odds ratio of 0.35 (95% Condifence interval=0.13-0.91, p=0.033) between the TT and AA polymorphisms, indicating a reduced risk of prostate cancer to be associated with the AA polymorphism. Subset analysis revealed no significant associations between this polymorphism and clinicopathological characteristics of prostate cancer. CONCLUSION: The results of this study demonstrated a relationship between the CAV1 T29107A variant and risk of prostate cancer. This polymorphism thus, merits further investigation as a potential genomic marker for the early detection of prostate cancer. Our results support the hypothesis that the CAV1 T29107A (rs7804372) polymorphism may influence susceptibility to prostate cancer; however, prostate cancer progression was not associated with this polymorphism in a Japanese population.

ADRB3 polymorphism associated with BMI gain in Japanese men.

OBJECTIVE: The aim of this study was to evaluate the association between the Trp64Arg polymorphism in the beta3-adrenergic receptor gene (ADRB3: rs4994) and BMI and serological and anthropometric data in healthy Japanese. METHODS: Healthy Japanese recruited in a large-scale integrated manufacturing facility in Japan (N = 1355; age: 37.25 ± 9.43; BMI: 22.86 ± 3.46) were eligible for analysis. The anthropometric data and serological data were measured during a comprehensive health check, and a self-reporting questionnaire was used to assess lifestyle habits (current exercise, smoking status, alcohol intake, and working style) and weight at age 20. Genotyping for the ADRB3 polymorphism was performed by PCR-RFLP method. RESULTS: Among 1355 participants, the genotype frequencies of the Trp/Trp, Trp/Arg, and Arg/Arg variants were 920 (67.9%), 394 (29.1%), and 41 (3.05%), respectively. In the multivariate analysis, a multiple linear regression model in men for the adjustment of age, drinking habits, smoking habits, exercise habits, working status and serological measurements statistically showed an overall weak significance between annual BMI gain from age 20 and age, LDL or ADRB3 polymorphism. CONCLUSIONS: The level of LDL, age, and ADRB3 polymorphism (Arg/Arg genotype) were statistically associated with annual BMI gain in Japanese men.

Genetic polymorphisms and oral cancer.

Oral cancer, a disease associated with major morbidity and mortality, represents a significant worldwide health problem. It is clear that the major etiological factors for oral cancer are tobacco and alcohol exposure. It has been shown that metabolic activation is associated with cancer susceptibility. Various carcinogens and carcinogenic precursors, such as benzopyrene and nitrosamine, have been identified in tobacco smoke, and those are activated or detoxified by two types of metabolic enzymes, phase I and phase II. There are some polymorphisms for these enzyme genes, the functions of which are modified by the types of polymorphisms. On the other hand, there are some genes besides these enzyme genes related to cancer susceptibility. In this review, we discuss the relationships between polymorphisms concerned with oral cancer. Although there are many reports on the polymorphisms related to oral cancer, the results of these reports are controversial. Further studies are needed to evaluate the interactions between carcinogens and the genetic polymorphisms.

DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population.

BACKGROUND: Bladder cancer is the most common urologic malignancy in the USA. Tobacco smoking generates oxidative DNA damage and induces bladder cancer. Base excision repair (BER) is a very important mechanism for repairing oxidative DNA damage. There are many enzymes involved in BER. Human oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing 1 (XRCC1) are enzyme genes of BER. Actually, the hOGG1 codon 326 polymorphism was associated with the risk of lung oesophagus and stomach cancer. On the other hand, among several XRCC1 gene polymorphisms, codon 399 polymorphism was reported to reduce the risk of bladder cancer and raise the risk of lung cancer. METHODS: We examined the association between the genetic polymorphisms of hOGG1 codon 326 and XRCC1 codon 399 and bladder cancer risk. In this study, we recruited 251 bladder cancer cases and 251 healthy controls to evaluate the effect of hOGG1 codon 326 and XRCC1 codon 399 polymorphisms on bladder cancer. We detected genotypes by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The frequencies of the hOGG1 codon 326 genotypes Cys/Cys was significantly higher in the cases than in the controls. Adjusted odds ratio (OR) was 1.85 (95% CI: 1.12-3.03; p = 0.02) compared with Ser/Ser, and was 2.05 (95% CI: 1.36-3.08; p = 0.01) compared with Ser/Ser + Ser/Cys. In addition, when evaluated with smoking status, the adjusted OR (Cys/Cys versus Ser/Ser + Ser/Cys) ran up to 2.78 (95% CI: 1.39-5.60; p < 0.01) among non-smokers. For the XRCC1 polymorphism, the Gln/Gln of XRCC1 codon 399 genotype was statistically higher in the controls than in the cases though compared with Alg/Alg + Alg/Gln. The adjusted OR was 0.45 (95% CI: 0.21-0.99; p = 0.05), and was lifted up to 0.37 (95% CI: 0.14-0.98; p = 0.05) among smokers. CONCLUSION: It is indicated that the hOGG1 codon 326 and XRCC1 codon 399 polymorphisms are risk factors of bladder cancer.

Association between the TP53 codon72 polymorphism and oral cancer risk and prognosis.

The TP53 codon72 polymorphism has recently been extensively studied to determine the risk factor for carcinogenesis. However, there are few reports about the relationship between the TP53 codon72 polymorphism and oral cancer risk or post treatment prognosis. We evaluated the genotypic distribution of the TP53 codon72 polymorphism in 100 oral cancer cases and 271 non-cancer controls. There were no significant differences in the frequencies of the three genotypes (Arg/Arg, Arg/Pro, Pro/Pro) of the TP53 codon72 polymorphism between oral cancer cases and controls. However, stratifying by smoking status, we found that the adjusted odds ratio for non-smokers with the Pro/Pro genotype was significantly increased (adjusted OR=2.70, 95% confidence interval=1.07-6.82). We also found that the cases with the Pro/Pro genotype tended to have a shorter post-treatment survival compared with those with the Arg/Pro genotype (p=0.06). Our results suggest the Pro/Pro genotype of the TP53 codon72 polymorphism increases oral cancer risk in non-smokers and worsens their prognosis.

[Investigation of the condition of asbestos in large-scale buildings in Kitakyushu].

Recently, asbestos-related diseases have become serious all over the world. We investigated the condition of asbestos in large-scale buildings. The survey was performed in 2006 in Kitakyushu with self-administered questionnaires which were sent to managers of 250 buildings. We received 150 answers. Eighteen buildings out of 150 used chrysotile or crocidolite, and 6 buildings out of 18 took measures to deal with the situation. The number of buildings where asbestos was used increases with the age of the buildings. The older the buildings are, the more buildings used asbestos, probably reflecting the extent of legal regulations and recognition of the harmfulness of asbestos. Twenty-one buildings out of 150 gave education on asbestos, 9 buildings out of 21 buildings used asbestos, and half the buildings didn't give education on asbestos. These results suggest that the measures against and education on asbestos are insufficient in large-scale buildings.

[Relationship of changes in radius bone mineral density during seven years in working women around thirty years old with lifestyle, body measurement data and laboratory data].

OBJECTIVES: A longitudinal study was conducted to investigate the relationships of the change in radius bone mineral density for seven years with lifestyle, body measurement data and laboratory data. METHODS: The subjects of this study were 191 female employees working in an LSI manufacturing factory in Japan. Bone mineral density was measured on the radius of their nondominant side using DXA (dual energy X-ray absorptiometry) in 1995 and 2002. Other medical examinations were performed at the same time. Multiple regression analysis was also performed with the change in radius bone mineral density as the dependent variable. RESULTS: As a result of the multiple regression analysis, a significant positive correlation was observed between the change in body mass index (BMI) and the change in bone mineral density among the subjects aged 30 years and over and those under 30 years. A significant positive correlation was observed between daily milk intake and the change in bone mineral density among those aged under 30 years. A significant negative correlation was observed between daily alcohol intake and the change in bone mineral density among those aged under 30 years, and also between parity and the change in bone mineral density among those aged 30 years and over. CONCLUSIONS: BMI, parity, daily milk intake and daily alcohol intake are considered as significant factors that contribute to a change in bone mineral density. It is necessary that the recommended timing for medical examination be set according to age, and that a well-balanced guidance be provided from young adulthood.

Type I interferon production by tertiary lymphoid tissue developing in response to 2,6,10,14-tetramethyl-pentadecane (pristane).

Lymphoid neogenesis is associated with antibody-mediated autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. Although systemic lupus erythematosus is the prototypical B-cell-mediated autoimmune disease, the role of lymphoid neogenesis in its pathogenesis is unknown. Intraperitoneal injection of 2,6,10,14-tetramethyl-pentadecane (TMPD, pristane) or mineral oil causes lipogranuloma formation in mice, but only TMPD-treated mice develop lupus. We report that lipogranulomas are a form of lymphoid neogenesis. Immunoperoxidase staining of lipogranulomas revealed B cells, CD4(+) T cells, and dendritic cells and in some cases organization into T- and B-cell zones. Lipogranulomas also expressed the lymphoid chemokines CCL21, CCL19, CXCL13, CXCL12, and CCL22. Expression of the type I interferon (IFN-I)-inducible genes Mx1, IRF7, IP-10, and ISG-15 was greatly increased in TMPD- versus mineral oil-induced lipogranulomas. Dendritic cells from TMPD lipogranulomas underwent activation/maturation with high CD86 and interleukin-12 expression. Magnetic bead depletion of dendritic cells markedly diminished IFN-inducible gene (Mx1) expression. We conclude that TMPD-induced lupus is associated with the formation of ectopic lymphoid tissue containing activated dendritic cells producing IFN-I and interleukin-12. In view of the increased IFN-I production in systemic lupus erythematosus, these studies suggest that IFN-I from ectopic lymphoid tissue could play a role in the pathogenesis of experimental lupus in mice.

[Consciousness survey regarding genetic diagnosis of glutathione S-transferase M1 (GSTM1) and aldehyde dehydrogenase 2 (ALDH2) polymorphism].

A Consciousness survey regarding genetic diagnosis of GSTM1 and ALDH2 was performed to evaluate the potential use of such a diagnosis in supporting those wanting to stop smoking and decrease alcohol intake. A questionnaire was given to 1,654 employees (male: 1,225, female: 429) who worked at an LSI manufacturing factory, and 1,434/1,654 (86.7%) responded to the survey. The number of respondents who replied that they "wanted to know the results of the genetic diagnosis of GSTM1 and ALDH2" were 731/1,401 (52.2%) and 812/1,434 (56.6%), respectively while the numbers of respondents who replied that they "did not want to know the results" were 138/1,401 (9.9%) and 103/1,434 (7.2%), respectively. The main reasons given for wanting to know the results of the genetic diagnosis of their enzymes reflected the respondents' awareness of their genetic susceptibility. These reasons included a desire to know the effects of tobacco smoke, to prevent diseases in the future, to know the effects of passive smoking or to know their tolerance for alcohol. On the other hand, the main reason for not wanting to know the genetic results that the respondents had no intention of stopping smoking and heavy drinking, or that they would be unable to stop even if they knew the results of the genetic diagnosis. Multiple regression analysis showed that the number of respondents who "wanted to know the results of the genetic diagnosis" was significantly higher among those respondents who are current smokers (male: OR = 1.66 95%CI 1.29-2.14, female: OR = 2.33 95%CI 1.37-3.98), those who understood the relationship between smoking and lung cancer (male: OR = 1.81 95%CI 1.25-2.63, female: OR = 2.77 95%CI 1.42-5.40) and those who with a high CAGE test score (male: OR = 1.96 95%CI 1.42-2.68, female: OR = 2.52 95%CI 1.07-5.94). The results of this survey suggest that genetic diagnosis of GSTM1 and ALDH2 polymorphism may be useful in supporting those who want to stop smoking and decrease their alcohol intake.