Biomedical subjects

Kazuko Nishio

Publications and source records attributed to Kazuko Nishio.

17 recordsLinked to original sources

PubMed2006

Grb2-associated binder 1 polymorphism was associated with the risk of Helicobactor pylori infection and gastric atrophy.

BACKGROUND: Various single nucleotide polymorphisms (SNPs) have explained the association between Helicobacter pylori (H. pylori) and gastric atrophy and cancer. This study investigated the associations of Grb2 associated binder 1 (Gab1) polymorphism and the combination of PTPN11 gene encoding src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP2) and Gab1 gene with gastric cancer and gastric atrophy among H. pylori seropositive subjects. METHODS: A single nucleotide polymorphism at intron 2 of Gab1 (JST164345) was examined for 454 Japanese health checkup examinees (126 males and 328 females) aged 35 to 85 without a history of gastric cancer and 202 gastric cancer patients (134 males and 68 females) aged 33 to 94 with pathologically confirmed diagnosis of gastric adenocarcinoma. RESULTS: The decreased OR of the Gab1 A/A for H. pylori seropositivity was 0.25 (95% confidence interval (CI): 0.08-0.71). Among seropositive healthy controls, the OR of the Gab1 G/A+A/A for gastric atrophy was significant (OR=1.95, 95% CI: 1.12 -3.40). Seropositive individuals with PTPN11 G/G and Gab1 G/A+A/A demonstrated the highest risk of gastric atrophy with significance (OR=3.49, 95% CI: 1.54-7.90) relative to PTPN11 G/A+A/A and Gab1 G/G, the lowest risk combination, as a reference. However, the gene-gene interaction between PTPN11 and Gab1 was not observed (OR=1.39, 95% CI: 0.41-4.66). Compared to gastric cancer case, the Gab1 did not influence the step of atrophy/metaplasia-gastric cancer sequence. CONCLUSIONS: This study represents that the Gab1 polymorphism was associated with the low risk of H. pylori infection and the high risk of gastric atrophy among seropositive healthy controls, and that seropositive individuals with PTPN11 G/G and Gab1 G/A+G/G were associated with the greatest risk of gastric atrophy. These findings require confirmation in much larger studies.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Eradication rate of Helicobacter pylori according to genotypes of CYP2C19, IL-1B, and TNF-A.

BACKGROUND: Lansoprazole, amoxicillin, and clarithromycin are commonly used drugs for eradication of Helicobacter pylori (H. pylori). A few studies reported that the eradication rate was influenced by the functional polymorphism of CYP2C19, whose product metabolizes proton pomp inhibitors including lansoprazole. METHODS: This study examined the eradication rate among 67 participants in the polymorphism study who visited Daiko Medical Center, Nagoya University from July 2004 to October 2005. The participants aged 20 to 69 years were classified into three group according to CYP2C19 genotype; rapid metabolizers (RM) with *1*1 genotype, intermediate metabolizers (IM) with *1*2 or *1*3 genotype, and poor metabolizers (PM) with *2*2, *2*3, or *3*3 genotype. For the genotype classification, G681A (681G for *1 and 681A for *2) and G636A (636G for *1 and 636A for *3) were genotyped by PCR with confronting two-pair primers (PCR-CTPP). They were also genotyped for IL-1B T-31C and TNF-A T-1031C by a duplex PCR-CTPP. RESULTS: The eradication rate was 70.0% for RM, 93.9% for IM, and 85.7% for PM. The difference in the rate between RM and IM+PM was statistically significant (p=0.025). The eradication rate was highest for those with IL-1B -31CC; the p value was marginal among the whole subjects (chi2=3.78, p=0.05) and not significant among the RM group (chi2=1.60, p=0.21). The genotypes of TNF-A T-1031C had no associations with the eradication rate. But among the RM group, the odd ratio (OR) of the TNF-A CT for the eradication rate relative to TT was marginally reduced (OR=0.05, 95% confidence interval, 0.002-1.19). CONCLUSIONS: The present study confirmed the low eradication rate for RM. The reproduced finding provides evidence that the CYP2C19 genotype is useful to predict the success of the treatment. For the RM group, alternative regimens expected to be with a higher eradication rate will be recommended, especially to those with the TNF-A -1031C allele.

Journal Article↗

PubMed2006

Alternative genotyping method of GSTT1 null/present polymorphism.

Glutathione S-transferase (GST) theta is an enzyme to detoxify xenobiotic compounds. The gene GSTT1 has a null/present polymorphism in one of the targets for cancer susceptibility research. The polymorphism is classified into two types: present type with at least one present allele (heterozygote and homozygote) and null type without a present allele. Although one report showed a method to distinguish the heterozygote from the present homozygote, its use has been limited possibly owing to the difficulty of successful genotyping of long DNA sequences (1460 base pairs). This article reports an alternative method utilizing typical PCR primers specific to the null allele (566 base pairs) and the present allele (458 base pairs). All samples of the GSTT1 null genotype processed by the present PCR method (n = 331), were correctly classified as the null genotype by a conventional method, and the samples of heterozygous (n = 364) or present homozygous (n = 108) genotype as the present genotype; this indicates that it is appropriate for future research to utilize three genotypes of the GSTT1 null/present polymorphism.

Disease↗

PubMed2005

Prospective study of alcohol consumption and breast cancer risk in Japanese women.

Epidemiologic evidence is lacking for the association between alcohol consumption and the risk of breast cancer in Japanese women. We addressed this association in a prospective cohort study with an average follow-up of 7.6 years. At baseline (1988-1990), cohort participants completed a self-administered questionnaire that included alcohol use, reproductive history and hormone use. The women were followed up for breast cancer incidence through December 31, 1997. Cox proportional hazards models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer incidence and any association with alcohol consumption. During a follow-up of 271,412 person-years, we identified 151 women with breast cancer, of whom 45 were current drinkers and 11 drank > or =15 g of alcohol/day. After adjustment for age and other potential risk factors for breast cancer, the RR for current drinkers was 1.27 (95% CI 0.87-1.84) compared to nondrinkers. Average alcohol intake of <15 g/day did not significantly increase the risk for breast cancer. However, risk was significantly increased for women who consumed > or =15 g/day of alcohol (RR = 2.93, 95% CI 1.55-5.54). Age at starting drinking and frequency of consumption per week were not significantly associated with breast cancer risk. Our cohort study demonstrated that Japanese women who consume at least a moderate amount of alcohol have an increased risk of breast cancer.

Adult↗

PubMed2005

Use of duplex PCR-CTPP methods for CYP2E1RsaI/IL-2 T-330G and IL-1B C-31T/TNF-A T-1031C polymorphisms.

BACKGROUND: Two duplex polymerase chain reaction (PCR) with confronting two-pair primer (PCR-CTPP) methods were designed for cytochrome P450 (CYP) 2E1 RsaI and interleukin (IL-2) T-330G, and for IL-1B C-31T and tumor necrosis factor-alpha (TNF-A) T-1031C. The four polymorphisms are considered to be functional, and the three cytokines reportedly inhibit CYP2E1 expression. Many studies have reported associations between the above polymorphisms and risk of diseases including cancers and inflammatory diseases. AIM: The main objective of this study was to examine the applicability of the established PCR conditions to a real situation. PARTICIPANTS: Participants were female examinees aged from 35 to 85 years who attended health checks run by a local government in Japan. RESULTS: The allele frequencies among 325 female health check examinees were 0.804 for CYP2E1 c1 allele, 0.668 for IL-2-330T allele, 0.554 for IL-1B-31T allele, and 0.822 for TNF-A-1031T allele. p-Values from a Hardy-Weinberg equilibrium test were 0.658, 0.955, 0.062, and 0.806, respectively. DISCUSSION: Clear DNA bands observed with electrophoresis allowed us to genotype the four polymorphisms. The genotype frequencies were within the Hardy-Weinberg equilibrium test proportions, though the p-value for IL-1B C-31T was marginal. CONCLUSIONS: Both duplex PCR-CTPP methods may be useful tools for studies on the association between these polymorphisms and disease risk.

Adult↗

PubMed2005

Possible interactions of the endothelial constitutive nitric oxide synthase genotype with alcohol drinking and walking time for high serum uric acid levels among Japanese.

A variable number of tandem repeat polymorphism located in intron 4 of the gene for endothelial constitutive nitric oxide synthase (ecNOS) is reported to be significantly associated with the nitric oxide level, which influences serum uric acid (SUA). To cast light on any association between the polymorphism and hyperuricemia, as well as gene-environment interactions, a cross-sectional study was conducted for 703 health checkup examinees (213 men and 490 women). The age-adjusted odds ratio (aOR) of hyperuricemia (> or =7 mg/dL) for ecNOS 4/4, 4/5, or 5/6 genotypes (non-5/5 group) as compared with the 5/5 genotype was 2.41 (95% confidence interval [CI], 1.09-5.30) in men. The aORs for drinking alcohol relative to never drinking were found to be 8.93 (95% CI, 1.02-78.16) among men with non-5/5 genotypes and 1.76 (95% CI, 0.59-5.26) for their 5/5 counterparts. Moreover, the aORs for heavy drinking (> or =50 mL/d) were 23.16 (95% CI, 2.14-250.35) and 2.48 (95% CI, 0.75-8.15), respectively. The interaction between the genotype and current drinking was 3.10 (95% CI, 0.45-21.41). The aORs for more than 30 minutes of daily walking relative to 30 minutes or less of daily walking were found to be 1.54 (95% CI, 0.40-5.95) among men with non-5/5 genotypes and 0.31 (95% CI, 0.12-0.81) for their 5/5 counterparts. The interaction between the genotype and more than 30 minutes of daily walking was 4.92 (95% CI, 0.95-25.64). This study indicated that the ecNOS variable number of tandem repeat polymorphism influences the SUA level in men. Although the interactions were not significant, alcohol intake may be more influential among men with non-5/5 genotypes and walking may be more effective among men with the 5/5 genotype. These findings would be informative for men with high SUA levels.

Adult↗

PubMed2005

Impact of menstrual and reproductive factors on breast cancer risk in Japan: results of the JACC study.

The incidence of breast cancer among Japanese women, a traditionally low-risk population, has increased substantially. To evaluate the association of reproductive factors with breast cancer risk, we examined 38,159 Japanese women, aged 40-79 years, who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study. During an average 7.6 years of follow-up, we documented 151 incidents of breast cancers. Cox proportional hazards modeling was employed to estimate relative risks (RR) and 95% confidence intervals (CI). There was a significant decline in the risk of breast cancer with increasing parity among parous women (trend P=0.01). Women with four or more parities had a 69% lower risk than uniparous women, a reduced risk was also evident among menopausal women. Breast cancer risk tended to rise with increasing age at first delivery (trend P=0.05), the association being very apparent among menopausal women (trend P=0.02). Compared to the women who had their first delivery before age 25, those who delayed this event until after age 34 had an RR of 2.12 (95% CI: 0.72-6.21) and 3.33 (1.07-10.3) among the overall subjects and the menopausal, respectively. There was no apparent association of breast cancer risk with age at menarche or menopause. Our study concerning reproductive risk factors suggests that breast cancer in Japan is similar to that in Western countries, and that reproductive factors, particularly the number of parity and age at first delivery, might be important in the etiology of breast cancer among Japanese women.

Adult↗

PubMed2005

Dietary intakes of fat and fatty acids and risk of breast cancer: a prospective study in Japan.

To examine the possible association of dietary fat and fatty acids with breast cancer risk in a population with a low total fat intake and a high consumption of fish, we analyzed data from the Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 26 291 women aged 40-79 years completed a questionnaire on dietary and other factors. Intakes of fat or fatty acids were estimated by using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow-up of 7.6 years, 129 breast cancer cases were documented. We found no clear association of total fat intake with breast cancer risk; the multivariate-adjusted RR across quartiles were 1.00, 1.29, 0.95, and 0.80 (95% confidence interval [CI] 0.46-1.38). A significant decrease in the risk was detected for the highest quartile of intake compared with the lowest for fish fat and long-chain n-3 fatty acids; the RR were 0.56 (95% CI 0.33-0.94) and 0.50 (0.30-0.85), respectively. A decreasing trend in risk was also suggested with an increasing intake of saturated fatty acids (trend P = 0.066). Among postmenopausal women at baseline, the highest quartile of vegetable fat intake was associated with a 2.08-fold increase in risk (95% CI 1.05-4.13). This prospective study did not support any increase in the risk of breast cancer associated with total or saturated fat intake, but it suggested the protective effects of the long-chain n-3 fatty acids that are abundant in fish.

Adult↗

PubMed2005

Cigarette smoking and the risk of ovarian cancer in the Japanese population: findings from the Japanese Collaborate Cohort study.

AIM: The many studies into the relation between cigarette smoking and the risk of ovarian cancer have produced inconsistent results. Here we investigated this relation using data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, initiated in 1988. METHODS: A self-administered questionnaire on smoking habits and other risk factors for cancer was completed by 34 639 Japanese women. After 7.6 years of follow up, 39 cases of ovarian cancer were available for analyses. Cox proportional-hazards models were used to compute relative risks (RR) and to adjust for confounders. RESULTS: Relative to those who had never smoked, the RR of ovarian cancer were 1.63 (95% confidence interval [CI] = 0.21-12.50) for former smokers and 2.27 (95% CI = 0.85-6.08) for current smokers. Among current smokers, the RR were 1.48 (95% CI = 0.20-10.92), 5.56 (95% CI = 1.68-19.06), and 1.86 (95% CI = 0.25-14.30) among women who smoked <10, 10-19, and at least 20 pack-years ([number of cigarettes smoked per day/20] x number of years subject has smoked), respectively, relative to those who had never smoked. A test for trend was statistically significant (P = 0.044). CONCLUSIONS: These data indicate that cigarette smoking increases the risk of developing ovarian cancer in the Japanese population.

Aged↗

PubMed2005

Relationship between body mass index and the risk of ovarian cancer in the Japanese population: findings from the Japanese Collaborate Cohort (JACC) study.

AIM: The incidence of ovarian cancer in Japan has increased since the 1970s. The many studies that have assessed the relationship between body mass index (BMI) and the risk of ovarian cancer have produced contradictory results. Here we investigated this relation using data from the Japan Collaborative Cohort Study for the Evaluation of Cancer Risk, which was initiated in 1988. METHODS: A self-administered questionnaire on dietary habits and other risk factors for cancer was completed by 36,456 Japanese women. After 7.6 years of follow up, 38 cases of ovarian cancer were available for analysis. Cox proportional-hazards models were used to compute relative risks and to adjust for confounders. RESULTS: Compared to women with BMI of 18.5-24.9 kg/m2, the relative risk of ovarian cancer was 2.24 (95% CI = 1.10-4.21) for BMI of 25.0-29.9 and 1.78 (95% CI = 0.24-13.34) for BMI of > or = 30 kg/m2. A test for trend revealed that this finding was statistically significant (P = 0.014). CONCLUSION: The results of this study suggest that being overweight is independently associated with a higher risk of developing ovarian cancer in the Japanese population.

Adult↗

PubMed2004

Genotype announcement in a genetic polymorphism study for health checkup examinees at Nagoya University Hospital.

On June 9, 2003, we started free genetic tests of eight polymorphisms for health checkup examinees who attended a basic course at Nagoya University Hospital. They were informed of their genotypes within four weeks after blood donation for research purposes. The genotypes were those of alcohol dehydrogenase 2 (ADH2) Arg47His, aldehyde dehydrogenase 2 (ALDH2) Glu487Lys, NAD(P)H: quinone oxidoreductase (NQO1) C609T, glutathione S transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), interleukin-1B (IL-1B) C-31T, and tumor necrosis factor A (TNF-A) T-1031C, angiotensin-converting enzyme (ACE) Ins/Del. In the first three months, 227 (89.4%) out of 254 examinees participated in the free tests, having been informed of the research aims, after which they consented to our use of research data. To date, there have been no complaints from the participants, indicating that the announcement of polymorphism genotypes may be accepted differently from that of hereditary disease genotypes.

Alcohol Dehydrogenase↗

PubMed2004

Associations between disease risk and eight polymorphisms adopted for genotype announcements at Nagoya University Hospital.

Genetic polymorphisms have the potential to predict disease susceptibility. This may be especially useful among individuals with a high-risk lifestyle, so that the genotyping could be adopted for disease prevention through modifications toward a lower-risk lifestyle. We started a program of free genotype announcements in a polymorphism study among health checkup examinees at the Nagoya University Hospital on June 9, 2003. Since such announcements remain controversial for fear of unexpected harmful effects and counseling system, the accumulated evidence on the association between disease risk and genotypes announcements in our study was reviewed in this article. The genotypes used were those of alcohol dehydrogenase 2 (ADH2) Arg47His, aldelhyde dehydlrogenase 2 (ALDH2) Glu487Lys, NAD(P)H: quinone oxidoreductase (NQO1) C609T, glutathlione S transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), interleukin-1B (IL-1B) C-31T, and tumor necrosis factor A (TNF-A) T-1031C, angiotensin converting enzyme (ACE) Ins/Del. Since showed a potential for widespread use in health checkups, the information on the above polymorphisms seems worth documenting. Although there have been no complaints from the participants to date, careful treatments are requested.

Alcohol Dehydrogenase↗

PubMedDate not supplied

Precise definition of anonymization in genetic polymorphism studies.

Anonymization is an essential tool to protect privacy of participants in epidemiological studies. This paper classifies types of anonymization in genetic polymorphism studies, providing precise definitions. They are: 1) unlinkable anonymization at enrollment without a participant list; 2) unlinkable anonymization before genotyping with a participant list; 3) linkable anonymization; 4) unlinkable anonymization for outsiders; and 5) linkable anonymization for outsiders. The classification in view of accessibility to a table including genotype data with directly identifiable data such as names is important; if such tables exist, staff may obtain genotype information about participants. The first three modes are defined here as anonymization unaccessible to genotype data with directly identifiable information for research staff. Anonymization with a key code held by participants is possible with any of the above anonymization modes, by which participants can access to their own genotypes through telephone or internet. A guideline issued on March 29, 2001 with collaboration of three Ministries in Japan defines "anonymization in a linkable fashion" and "anonymization in an unlinkable fashion", "for the purpose of preventing the personal information from being divulged externally in violation of law, the present guidelines or a research protocol", but the contents are not clear in practice. The proposed definitions will be useful when we describe and discuss the preferable mode of anonymization for a given polymorphism study.

Anonymous Testing↗

PubMedDate not supplied

Helicobacter pylori eradication as a preventive tool against gastric cancer.

Helicobacter pylori (H. pylori), which increases the risk of gastric diseases, including digestive ulcers and gastric cancer, is highly prevalent in Asian countries. There is no doubt that eradication of the bacterium is effective as a treatment of digestive ulcer, but eradication aiming to reduce the gastric cancer risk is still controversial. Observational studies in Japan demonstrated that the eradication decreased the gastric cancer risk among 132 stomach cancer patients undergoing endoscopical resection (65 treated with omeprazol and antibiotics and 67 untreated). In Columbia, 976 participants were randomized into eight groups in a three-treatment factorial design including H. pylori eradication, resulting in significant regression in the H. pylori eradication group. A recent randomized study in China also showed a significant reduction of gastric cancer risk among those without any gastric atrophy, intestinal metaplasia, and dysplasia. Efficacy of eradication may vary in extent among countries with different incidence rates of gastric cancer. Since the lifetime cumulative risk (0 to 84 years old) of gastric cancer in Japan is reported to be 12.7% for males and 4.8% for females (Inoue and Tominaga, 2003), the corresponding values for H. pylori infected Japanese can be estimated at 21.2% in males and 8.0% in females under the assumptions that the relative risk for infected relative to uninfected is 5 and the proportion of those infected is 0.5. Both the fact that not all individuals are infected among those exposed and the knowledge that only a small percentage of individuals infected with the bacterium develop gastric cancer, indicate the importance of gene-environment interactions. Studies on such interactions should provide useful information for anti-H. pylori preventive strategies.

Anti-Bacterial Agents↗

PubMedDate not supplied

GSTT1 and GSTM1 deletions, NQO1 C609T polymorphism and risk of chronic myelogenous leukemia in Japanese.

We conducted a prevalent case-control study with 51 chronic myelogenous leukemia (CML) cases and 476 controls to investigate the associations between glutathione S-transferase T1 (GSTT1), glutathione S-transferase M1 (GSTM1) deletions, and the NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism with risk of chronic myelocytic leukemia in Japanese. For the GSTT1 deletion, when the GSTT1 positive genotype was defined as the reference, the OR for the GSTT1 deletion genotype was 1.32 (95%CI; 0.74-2.36). For the GSTM1 deletion, when the GSTM1 positive genotype was defined as the reference, the OR for the GSTM1 deletion genotype was 0.95 (95%CI; 0.53-1.69). For NQO1 C609T polymorphism, when the NQO1 609CC genotype was defined as the reference, the ORs for the CT genotype, TT genotype, and CT and TT genotypes combined together were 2.37 (95%CI, 1.21-4.67, P=0.012), 1.44 (0.55-3.74, P=0.012) and 2.12 (1.10-4.08, P=0.025), respectively. The present study revealed that the risk of CML was modulated little by GSTT1 and GSTM1 deletions, but a statistically significant association between NQO1 C609T polymorphism and CML was observed for Japanese. Incidence case-control studies with a larger statistical power are now required to confirm our findings.

Adolescent↗

PubMedDate not supplied

Multiplex PCR with confronting two-pair primers for CYP1A1 Ile462Val, GSTM1, GSTT1, and NQO1 C609T.

Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) is an effective genotyping method for single nucleotide polymorphisms (SNPs) in aspects of reducing time and costs for analysis. So far we have established PCR-CTPP conditions for tens of SNPs, including a triplex genotyping (Kawase et al., 2003). In the present study we report a quadruplex PCR-CTPP to genotype simultaneously four functional polymorphisms of carcinogen-metabolizing enzymes, CYP1A1 Ile462Val, GSTM1 null, GSTT1 null and NQO1 C609T, which were reported that they have significant associations with smoking-related cancers. We applied this method for 475 health check-up examinees to demonstrate the performance. Among the subjects, the genotype frequency of CYP1A1 Ile462Val was 56.8% for Ile/Ile, 38.1% for Ile/Val and 5.1% for Val/Val. The null type frequencies of GSTM1 and GSTT1 were 52.8% and 49.9%, respectively. And the genotype frequency of NQO1 C609T was 41.9% for C/C, 41.3% for C/T and 16.8% for T/T. Their distributions were similar to those reported for Japanese by other studies. To the best of our awareness, this is the first paper that reports the success in quadruplex PCR-CTPP. The applied polymorphisms are useful ones, which would be adopted not only for research purposes, but also for risk assessment of individuals exposed to carcinogenic substances. This convenient genotyping would be applied for cancer prevention especially in Asian Pacific regions, where expensive genotyping methods are hardly available.

Cytochrome P-450 CYP1A1↗

PubMedDate not supplied

The ACE gene polymorphism is associated with the incidence of gastric cancer among H. pylori seropositive subjects with atrophic gastritis.

Studies of the angiotensin converting enzyme (ACE) I/D polymorphism have provided evidence that the D/D genotype is associated with gastric tumor progression and numbers of lymph node metastases, but not with the overall risk of gastric cancer. The highest levels of circulating and tissue ACE activity were found in carriers of the D/D genotype. Here, we further investigated the association using 454 Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The ACE polymorphism was not found to be linked with H. pylori seropositivity or gastric atrophy. However, among H. pylori seropositive subjects with atrophy, those with the I/D genotype had an increased risk of gastric cancer (OR=1.59; 95% CI, 1.02-2.48). We also established that the polymorphism did not lower the age at diagnosis of gastric cancer. Confirmation of the association between ACE polymorphisms and development of gastric cancer requires much larger studies, and the biological role also needs to be fully elucidated.

Adenocarcinoma↗