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Biomedical subjects

Nobuyuki Hamajima

Publications and source records attributed to Nobuyuki Hamajima.

At least 91 records · Page 5Linked to original sources
PubMed2003

Physical exercise reduces risk of breast cancer in Japanese women.

To evaluate the effects of physical exercise on breast cancer risk, a large-scale case-referent study of 2376 incident breast cancer cases and 18,977 non-cancer referents was conducted using data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). To adjust appropriately for possible confounders, we examined the effects within subgroups of the study population. The multivariable-adjusted odds ratio (OR) was 0.81 (95% confidence interval (CI): 0.69-0.94) for twice a week or more regular exercise. We observed a decreased risk of breast cancer for women who regularly exercised for health twice a week or more, irrespective of menopausal status, and were able to detect greater risk reductions within particular subgroups, including women who were parous, without a family history or non-drinkers. Among premenopausal women, a particularly strong protective effect of physical exercise was observed (OR=0.57, 95%CI: 0.28-1.15) for those women whose body mass index (BMI) was high (BM > or = 25). In contrast, risk reduction was found (OR=0.71, 95%CI: 0.50-1.01) among postmenopausal women whose BMI was medium (BMI: 22-25). Stratification of history of stomach cancer screening to adjust modifying effects of healthy consciousness allows a more precise assessment of the protective effect of exercise twice a week or more, independent of stomach cancer screening history. This study provides evidence that physical exercise, especially exercise twice a week or more, reduces the risk of breast cancer among Japanese women.

Adult↗
PubMed2003

Association of CYP2A6 gene deletion with cigarette smoking status in Japanese adults.

BACKGROUND: Genetic variation of CYP2A6 is shown to alter nicotine metabolism. This study was developed to investigate the genetic influence of the whole deletion-allele of CYP2A6 on active and passive smoking behavior. METHODS: Two hundred and forty Japanese adults, who visited Aichi Cancer Center as outpatients, were genotyped for the wild-type (CYP2A6*1A, CYP2A6*1B) and the whole deletion-type (CYP2A6*4C) polymorphism of CYP2A6. Information about active and passive smoking status was obtained by a self-administered questionnaire. Genetic influence of CYP2A6 polymorphism on smoking behavior was evaluated using the Mantel extension test. RESULTS: The frequency of the deletion allele was 18%. All 8 subjects carrying two deletion alleles had no smoking habit, and the homozygous deletion genotype showed a tendency to correlate with active smoking status after adjustment for sex and age (p = 0.054). However, the proportion of never smokers among heterozygous subjects was almost the same as among subjects carrying no deletion allele (54% and 58%, respectively). Furthermore, CYP2A6 genotypes were correlated neither with the number of cigarettes smoked per day nor with the age at starting smoking (p = 0.364 and 0.880, respectively). Among never smokers, CYP2A6 genotypes were not correlated with exposure to passive smoking at home or in the workplace (p = 0.623 and 0.484, respectively). CONCLUSION: Despite the possible protection against active smoking behavior in subjects homozygous for the deletion allele, the CYP2A6 polymorphism has only a limited impact on public health because no protective effect was found in heterozygous subjects.

Adult↗
PubMed2003

Associations between polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and susceptibility to malignant lymphoma.

BACKGROUND AND OBJECTIVES: Polymorphisms in thymidylate synthase (TS) 28-bp tandem repeats in the promoter region and in cytosolic serine hydroxymethyltransferase (SHMT1 C1420T) have been reported to modulate the risk of adult acute lymphocytic leukemia (ALL). We examined the associations between susceptibility to malignant lymphoma and these polymorphisms. DESIGN AND METHODS: A hospital-based prevalent case-control study was conducted in Aichi Cancer Center. One hundred and eight patients with histologically confirmed lymphoma and 494 control subjects without cancer were evaluated. RESULTS: In a risk estimation of each genotype, those who harbored at least one TS 2 repeat (2R) allele had a 1.6-fold increase in the risk of malignant lymphoma (OR=1.63; 95%CI, 1.05-2.53, p=0.030) when using those without the TS 2R allele as a reference. For the SHMT1 C1420T polymorphism, those harboring at least one T allele showed a 2.2-fold decrease in risk (OR =0.46; 95% CI, 0.23-0.93, p=0.031). Moreover, combined analysis of TS and SHMT1 polymorphisms revealed that the OR for lymphoma in patients with SHMT1 1420 CC and the TS 2R allele, which might be expected to provide the basis for the highest susceptibility, was 2.88 (95% CI, 1.26-6.58, p=0.013). INTERPRETATIONS AND CONCLUSIONS: This study suggests that genetic traits involving low penetrance polymorphisms in folate-metabolizing genes may modulate the risk of malignant lymphoma.

Adult↗
PubMed2003

[Genetic polymorphisms related to interleukin-1 beta production and disease risk].

PURPOSE: Interleukin (IL)-1A C-889T, IL-1B C-511T, IL-1B C-31T, IL-1B C3954T, and IL-1RN 86-bp VNTR (variable number of tandem repeats) are polymorphisms potentially influencing IL-1 beta production. This review summarizes 1) the biological roles of IL-1 beta, 2) allele frequencies of the polymorphisms, and 3) the reported associations between these polymorphisms and disease risk. METHODS: Papers were obtained from PubMed with keywords "IL-1, polymorphism", as well as from the references in each paper. The most relevant papers were then selected. In this review, a narrative approach was adopted. RESULTS: IL-1 beta is a multifunctional proinflammatory cytokine, whose signal is transduced through IL-1 receptor I (IL-1RI) on the cell surface. Binding levels are influenced by the IL-1 receptor antagonist (IL-1Ra), IL-1RII (decoy receptor with no signal transduction), soluble IL-1RI, and soluble IL-1RII. IL-1B encoding IL-1 beta is located on chromosome 2q14, along with IL-1A encoding IL-1 alpha and IL-1RN encoding IL-1Ra. The minor alleles, IL-1A-889T, IL-1B 3954T, and IL-1RN 2R, are rarer in Japanese than in Caucasians, while IL-1B-511T and IL-1B-31C are more frequent. These polymorphisms have been reported to have potential associations with the risk of diseases, such as stomach cancer, breast cancer, inflammatory bowel, Alzheimer's, and osteoporosis. DISCUSSION: Although there are many inconsistent findings on associations with the polymorphisms, IL-1B C-511T and the tightly linked T-31C may be useful for predicting the risk of diseases with an inflammation basis among Japanese.

Genetic Predisposition to Disease↗
PubMed2003

Development of a food frequency questionnaire in Koreans.

We describe the development of a data-based food frequency questionnaire (FFQ) to determine the relationship between dietary intakes and diseases among Koreans. A total of 224 individuals were recruited to participate in a three-day dietary record survey. In all, 596 food items were consumed. The intakes of 20 nutrients including energy, protein, fat, carbohydrate, vitamins, minerals, and crude fibre were calculated for each food item by multiplying the weight of food consumed by its nutrient content. Some foods, consumed less than five times in a total of three days, were deleted from the preliminary food item list. The number of foods accounting for up to 90 cumulative percentage contribution to nutrient intake was 314. One hundred and seventy seven foods that accounted for up to 0.90 cumulative multiple regression coefficients and 90 cumulative percentage contribution were then selected. By grouping foods, 94 food items were finally included in the questionnaire: Grains and their products (15 food items), potatoes and starch (4), seeds (1), soybean, soybean products and other beans (4), vegetables (22), mushrooms (2), fruits (13), meats (7), eggs (1), fish (7), shellfish (4), other fish (2), seaweed (2), milk and dairy products (4), and beverages (6). Intake frequencies were classified into eight categories. Portion size was determined from food consumption reports in the three-day records. The mean percentage coverage of the 20 nutrient intakes by the developed FFQ was 82.4%. This questionnaire may be useful for ranking diet-related risk factors in Koreans.

Databases as Topic↗
PubMed2003

Calibration of a food frequency questionnaire in Koreans.

The current trend of changes in nutrient intakes may have some relationship with the increase in the occurrence of degenerative diseases in the Korean population. To date, a calibrated food frequency questionnaire (FFQ) has not been developed that can be further used for large-scale epidemiological research in Koreans aged 40 and older. This study was undertaken to develop and calibrate an FFQ in Koreans. A total of 144 Koreans aged 40 years and above participated in the first phase, which was conducted using the three-day dietary record method. One hundred and thirty-eight of those who completed the first phase were then interviewed to test FFQ against dietary records as a reference. The mean absolute nutrient intakes estimated by the dietary records were statistically compared with those estimated by the FFQ using paired t-tests. The mean values from the FFQ differed at most by 14% from those of the dietary records for all nutrients with the exception of vitamin A. Spearman rank-order correlation coefficients and cross-classification were also calculated. The energy-adjusted and corrected correlations for attenuation varied from 0.36 to 0.82. The degree of good agreement by cross-classification between the dietary records and the FFQ ranged from 67% to 90%. The newly developed FFQ can be used as a dietary assessment tool to measure usual nutritional status of Koreans aged 40 years and older. Furthermore, this study demonstrates that the FFQ also provides a more labour-efficient tool that is easier to use than any of the commonly used methods for large-scale epidemiological studies of the relationships between nutrition and diseases in Koreans.

Adult↗
PubMed2003

[A new genotyping method, PCR-CTPP].

The polymerase chain reaction with confronting two-pair primers (PCR-CTPP) is an inexpensive genotyping method, which is applicable for most single nucleotide polymorphisms(SNPs). In this method, allele-specific DNA products are amplified by applying appropriately designed two-pair primers (four primers) into a conventional PCR tube, followed by agarose gel electrophoresis. Duplex or triplex PCR-CTPP is also possible in a single tube, which reduces time and costs. An example of multiplex PCR-CTPP is described for NQO1 C609, GSTM1, and GSTT1. This convenient genotyping tool may be useful in health checkup to detect high risk individuals for some diseases, and to prevent such individuals from developing the diseases.

Alleles↗
PubMed2003

Detection of myelodysplastic syndrome/ acute myeloid leukemia evolving from aplastic anemia in children, treated with recombinant human G-CSF.

BACKGROUNDS AND OBJECTIVES: Recombinant human granulocyte colony-stimulating factor (G-CSF) has clear benefits in patients with severe neutropenia. However, recent reports of myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) developing after treatment with immunosuppressants and G-CSF has raised concern over the use of this agent in patients with aplastic anemia. DESIGN AND METHODS: We undertook a multi-institutional, non-randomized study of 112 children given a diagnosis of aplastic anemia, and then treated with different immunosuppressants with or without G-CSF. In each case, bone marrow specimens were tested at study entry and every 6 months for 3 years to detect t-MDS/AML, defined by stringent morphological and molecular/cytogenetic criteria. Incidence rates were calculated by the person-years statistical method. RESULTS: As of December 2001, all eligible patients had been followed for a median of 3 years, and the G-CSF (+) group had received a median total G-CSF dose of 30,100 micrograms altogether, administered over a median of 4 months. Only one case of MDS developed among the G-CSF (+) patients (n=81), compared with three in the group receiving other agents (n=31). This isolated case was not associated with monosomy 7, the cytogenetic abnormality most often linked to G-CSF treatment. Incidence rates of MDS in the two groups were not significantly different (3.8 vs. 22.4 per 1,000 patient-years at risk, p=0.125). There were no cases of overt AML in either cohort. INTERPRETATION AND CONCLUSIONS: G-CSF therapy did not increase the risk of t-MDS/AML development in children with aplastic anemia over a median follow-up of 3.7 years

Acute Disease↗
PubMed2003

Persistent Helicobacter pylori infection and genetic polymorphisms of the host.

Helicobacter pylori (HP) infection elevates the risk of gastric diseases including peptic ulcer and gastric cancer. The infection induces inflammatory cytokines, which could work both for and against lifetime infection in the human stomach. Genetic polymorphisms of the cytokines and other related ligands, receptors, and enzymes may influence persistent HP infection. This paper summarizes studies done on the associations between anti-HP antibody seropositivity and polymorphism genotypes. To date, the associations with the polymorphisms of fucosyl transferase 2 (FUT2 or secretor gene), FUT3 (Lewis gene), interleukin 1A (IL-1A), IL-1B, IL-1RN, IL-8, IL-10, myeloperoxidase (MPO), and tumor necrosis factor A (TNF-A) and TNF-B have been reported. Polymorphisms of other related genes, CD14, CXC chemokine receptor 2 (CXCR2), IL-1RI, nuclear factor KB2 (NF-KB2), and Toll-like receptor 4 (TLR4), have the potential to influence persistent infection. Unpublished results from our datasets are reported here for all these polymorphisms except TLR4. Gene-environment interactions between these genotypes and smoking are reviewed. An effect on OR due to the involvement of unexposed subjects is demonstrated to elucidate a disadvantage in the studies done in areas where the majority of the population is not exposed to HP.

Alleles↗
PubMed2002

No associations of p73 G4C14-to-A4T14 at exon 2 and p53 Arg72Pro polymorphisms with the risk of digestive tract cancers in Japanese.

A case-control study was conducted to examine the possible association between digestive tract cancers and p73 G4C14-to-A4T14 at exon 2 and p53 Arg72Pro polymorphisms in Japanese. Cases were 102 esophageal cancer patients, 144 stomach cancer patients, and 147 colorectal cancer patients, and controls were 241 non-cancer outpatients. The genotype frequencies among controls were 55.3% for p73 GG at position 4, 40.4% for GA, and 4.3% for AA, and 37.7% for p53 ArgArg, 44.4% for ArgPro, and 18.0% for ProPro. No significant differences in the genotype frequencies were observed between the controls and each case group or cases as a whole.

Adult↗
PubMed2002

The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors.

To improve the clinical outcome of allogeneic hematopoietic stem cell transplantation from an unrelated donor, the identification of human leukocyte antigen (HLA) alleles responsible for immunologic events such as graft-versus-host disease (GVHD), engraftment failure, and graft-versus-leukemia effect is essential. Genomic typing of HLA-A, -B, -C, -DRB1, and -DQB1 was retrospectively performed in 1298 donor-patient pairs in cases where marrow was donated from serologically HLA-A, -B, and -DR compatible donors. Single disparities of the HLA-A, -B, -C, or -DRB1 allele were independent risk factors for acute GVHD, and the synergistic effect of the HLA-C allele mismatch with other HLA allele mismatches on acute GVHD was remarkable. HLA-A and/or HLA-B allele mismatch was found to be a significant factor for the occurrence of chronic GVHD. HLA class I (A, B, and/or C) allele mismatch caused a significantly higher incidence of engraftment failure than HLA match. Significant association of HLA-C allele mismatch with leukemia relapse was not observed. As the result of these events, HLA-A and/or HLA-B allele mismatch reduced overall survival remarkably in both standard-risk and high-risk leukemia cases, whereas the HLA-C mismatch or HLA-class II (DRB1 and/or DQB1) mismatch did not. Furthermore, multiple mismatch of the HLA locus was found to reduce survival in leukemia cases. Thus, the role of the HLA class I allele in unrelated bone marrow transplantation was elucidated. Notably, HLA-C alleles had a different mode from HLA-A or -B alleles for acute GVHD and survival.

Adult↗
PubMed2002

A49T, V89L and TA repeat polymorphisms of steroid 5alpha-reductase type II and breast cancer risk in Japanese women.

BACKGROUND: Breast cancer is hormone related, as are cancers of the endometrium, ovary, and prostate. Several studies have suggested that higher extracellular levels of androgens are associated with breast cancer risk, while biological evidence indicates that androgens are protective. The codon 49 alanine to threonine substitution (A49T), codon 89 valine to leucine substitution (V89L) and TA repeat polymorphisms of the steroid 5alpha-reductase type II (SRD5A2) gene are considered functional with respect to enzyme activity converting testosterone into dihydrotestosterone. To test the hypothesis that these three polymorphisms are associated with risk of breast cancer, a case-control study was conducted with patients of Aichi Cancer Center Hospital. METHODS: The cases were 237 patients histologically diagnosed with breast cancer, and the controls were 185 noncancer outpatients. DNA from peripheral blood was genotyped by PCR methods. RESULTS: The threonine allele of A49T was not found in our subjects. Compared with the V/V genotype of V89L, the L/L genotype was associated with a decreased risk (crude odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.36-1.05). This was also the case for the TA(9/9) genotype, with an OR of 0.58 (95% CI = 0.13-2.63) relative to TA(0/0). Among women with the TA(0/0) genotype, however, the OR for the L/L genotype was 0.46 (95% CI = 0.24-0.88) compared with the V/V genotype, and those with the V/V and TA(0/0) genotypes had the highest risk. The haplotype with the L and TA(9) repeat alleles was not found. CONCLUSION: This study is the first to our knowledge focusing on Japanese women, suggesting that SRD5A2 polymorphisms might have an association with breast cancer risk. Further large-sample studies will be required to confirm the association and to assess any interactions with environmental factors.

Adult↗
PubMed2002

Height, weight, menstrual and reproductive factors and risk of gastric cancer among Japanese postmenopausal women: analysis by subsite and histologic subtype.

To clarify whether reproductive factors have an impact on gastric cancer in Japanese females, a case-control study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. The study subjects included 365 postmenopausal women with gastric cancer and 1,825 age-class frequency-matched noncancer outpatients presenting at Aichi Cancer Center in 1988-1998. Cases were further divided with regard to the anatomic subsite (upper third, middle third, lower third) and histologic subtypes (differentiated, nondifferentiated) and the association was evaluated using odds ratios (ORs) estimated by the logistic regression model, adjusting for potential confounding factors. A high body weight and corresponding body mass index at age 20 moderately increased the risk of gastric cancer, especially for middle third and nondifferentiated cancers. Risk fluctuation with early or late age at menarche and menopause and total duration of fertility was not consistent. Individuals with a high age at first parity tended to show decreased risk of cancer, irrespective of their subsite or histologic subtype. The ORs were decreased with a short average period of breastfeeding, especially for upper third and nondifferentiated cancers. From these results, however, it appears that height, weight, menstrual and reproductive factors have less impact on gastric cancer than environmental factors such as smoking and dietary habits or family history of gastric cancer.

Adult↗
PubMed2002

Lack of consistency in the associations of Helicobacter pylori seropositivity with Se and Le polymorphisms among Japanese.

BACKGROUND: In our previous study, a marked association between Helicobacter pylori seropositivity and functional polymorphisms of the secretor and Lewis genes (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.14-0.70 for se/se genotype relative to Se/Se genotype; and OR, 10.3; 95% CI, 3.16-33.8 for high-risk group defined by the combination of Se and Le relative to low-risk group) had been observed for 239 non-cancer Japanese outpatients of the gastroenterology clinic (OGC) undergoing gastroscopy at Aichi Cancer Center Hospital. METHODS: The present study was a confirmatory study to examine the association for 679 first-visit outpatients (FVO) of all clinics at the same cancer hospital and for 465 health checkup examinees (HCE) in the same city. RESULTS: The associations between H. pylori seropositivity and the Se and Le genotypes were nonsignificant or even in the opposite direction among the FVO (OR, 1.52; 95% CI, 1.00-2.32 for se/se genotype relative to Se/Se genotype; and OR, 0.77; 95% CI, 0.43-1.40 for the high-risk group defined similarly to the previous study), and among the HCE (OR, 1.25; 95% CI, 0.75-2.07; and OR, 1.07; 95% CI, 0.50-2.26, respectively). The discrepancy between the previous and present results was not explained by the difference in the distributions of age, sex, smoking, and H. pylori seroprevalence. CONCLUSION: Even in the same ethnic group, different sources of subjects may demonstrate inconsistent findings due to an unidentified effect modification. Inconsistent findings have rarely been reported by the same research group, but they are very important to understand the whole picture of the association under study.

Adolescent↗
PubMed2002

NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism and the risk of eight cancers for Japanese.

BACKGROUND: NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T was reportedly associated with leukemia, lung cancer, colorectal cancer, and urological malignancies. This study was conducted to screen possible cancer sites associated with this polymorphism by a prevalent case-control design. METHODS: The cases were 102 patients with esophageal cancer, 143 with stomach cancer, 74 with colon cancer, 72 with rectal cancer, 192 with lung cancer, 237 with breast cancer, 56 with prostate cancer, and 108 with malignant lymphoma. Controls consisted of outpatients from two sources: 241 noncancer outpatients who underwent gastroscopy and 399 first-visit outpatients, expected to include about 20% with cancer. Genotyping was conducted by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). RESULTS: The TT genotype with null enzyme activity was found in 19.9% of the 241 noncancer gastroscopy examinees, 16.5% of the 399 first-visit outpatients, 12.7% of the esophageal cancer patients, 16.8% of the stomach cancer patients, 13.5% of the colon cancer patients, 9.7% of the rectal cancer patients, 17.7% of the lung cancer patients, 14.3% of the breast cancer patients, 16.1% of the prostate cancer patients, and 15.7% of the malignant lymphoma patients. The odds ratios (ORs) of the genotypes were not significant for any cancers combined or for any site of cancer, except for lung cancer (OR, 0.66; 95% confidence interval [CI], 0.46-0.96 for CT relative to CC). The OR of current smoking for cancers of the esophagus and lung combined was different between the CC genotype (OR, 2.06; 95% CI, 1.06-3.98) and TT genotype (OR, 5.11; 95% CI, 1.37-19.05), although the difference was not significant. CONCLUSION: This study suggests that the CC genotype of the NQO1 C609T polymorphism is associated with the risk of lung cancer, and that the TT genotype increases the risk of smoking for cancers of the esophagus and lung.

Adenocarcinoma↗
PubMed2002

Competitive amplification and unspecific amplification in polymerase chain reaction with confronting two-pair primers.

Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) is an inexpensive, time-saving genotyping method that is applicable for most single nucleotide polymorphisms. To date, we have applied PCR-CTPP successfully for the genotyping of more than 30 polymorphisms. This paper demonstrates the differences in DNA amplification among different annealing temperatures of PCR-CTPP with given melting temperatures for four primers. The NQO1 C609T (Pro187Ser) polymorphism was used as an example. Two sets of four primers were applied for PCR-CTPP; the first set with different melting temperatures (Tms), and the second with similar Tms. The comparisons with one-pair primer PCR (allele-specific PCR) revealed that PCR-CTPP amplified DNA more specifically than allele-specific PCR. The primers with different Tms caused competitive DNA amplification for heterozygous genotype. Four primers with similar Tms amplified both alleles unspecifically at a lower annealing temperature, while the same DNA samples were correctly genotyped under an optimal annealing temperature. These findings are unique for PCR-CTPP, and important characteristics when the primers and annealing temperatures in PCR-CTPP are designed. The knowledge of these characteristics will extend the applicability of PCR-CTPP for polymorphism genotyping.

DNA Primers↗
PubMed2002

Efficacy of granulocyte colony-stimulating factor in the treatment of acute myelogenous leukaemia: a multicentre randomized study.

To investigate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in patients with acute myelogenous leukaemia, a multicentre randomized study was performed. From October 1993 to September 1996, 270 patients with newly diagnosed acute myelogenous leukaemia were randomized to G-CSF or control groups after remission induction therapy. The G-CSF group received G-CSF (Filgrastim) from 48 h after the completing chemotherapy until the absolute neutrophil count exceeded 1.5 x 10(9)/l. The control group did not receive G-CSF unless severe infection occurred. There were 245 evaluable patients (120 and 125 in the G-CSF and control groups respectively). The complete remission rate was similar in the G-CSF and control groups (80.8% versus 76.8%), as was the 5-year probability of disease-free survival (34.5% versus 33.6%) and overall survival (42.7% versus 35.6%). Neutrophil recovery was significantly faster in the G-CSF group than in the control group (12 d versus 18 d, P = 0.0001). The median duration of febrile neutropenia was significantly shorter in the G-CSF group than in the control group (3 d versus 4 d, P = 0.0001). In conclusion, prophylactic administration of G-CSF after remission induction therapy for acute myelogenous leukaemia is safe and useful even in patients without infection on completing chemotherapy.

Adolescent↗