Biomedical subjects

Keitaro Matsuo

Publications and source records attributed to Keitaro Matsuo.

At least 19 recordsLinked to original sources

PubMed2025

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

East Asian never smokers↗

PubMed2007

Risk factors differ for non-small-cell lung cancers with and without EGFR mutation: assessment of smoking and sex by a case-control study in Japanese.

The present study aimed to assess the impact of smoking and sex for the risk of non-small-cell lung cancer (NSCLC) with or without epidermal growth factor receptor (EGFR) mutation. We conducted a case-control study using 152 patients with EGFR-mutated (EGFRmut) NSCLC, 283 with EGFR-wild-type (EGFRwt) NSCLC and 2175 age- and sex-frequency-matched controls. Smoking was a significant risk factor for EGFRwt NSCLC (odds ratio [OR] for ever-smokers, 4.05; 95% confidence interval [CI], 2.79-5.88) but not for EGFRmut NSCLC (OR, 0.73; CI, 0.46-1.14). Sex did not affect this association. The association was observed consistently with other smoking-related parameters including pack-years. Sex was the sole risk factor for EGFRmut NSCLC (OR for women relative to men, 2.19; CI, 1.41-3.39) and there was no significant interaction between women and smoking. In contrast, sex, smoking and their interaction were significant in EGFRwt NSCLC. The impact of sex on EGFR mutation status was assessed by several indicators of reproductive history among women. Total fertile years showed a significant positive association with EGFRmut NSCLC but not with EGFRwt NSCLC. Other indicators showed similar trends and this result may partly explain the sexual difference in the acquisition of EGFR mutation. In conclusion, our case-control study clearly demonstrated that the impacts of smoking and sex on the risk of EGFRmut NSCLC are different from those for EGFRwt NSCLC. Further epidemiological evaluation is warranted.

Aged↗

PubMed2006

Lymphotoxin-alpha polymorphisms and the risk of endometrial cancer in Japanese subjects.

OBJECTIVE: To test the association of endometrial cancer with the lymphotoxin-alpha (LTalpha) C804A and A252G polymorphisms, a hospital-based incident case-control study was performed in Japanese subjects. METHODS: The cases comprised 110 endometrial cancer patients, and the controls were 220 age-matched cancer-free females. RESULTS: The LTalpha C804A and A252G polymorphisms were in complete linkage disequilibrium. We performed conditional logistic regression analysis adjusted for age, which revealed that the LTalpha 252AG and 804CA variant genotypes were associated with a significantly reduced risk of endometrial cancer (OR=0.51, 95% CI=0.31-0.86, P=0.011). Being homozygous of the LTalpha 252G and 804A alleles was not associated with the risk of endometrial cancer. However, the presence of at least one variant LTalpha allele was associated with a significantly lower risk of endometrial cancer (OR=0.54, 95% CI=0.33-0.87, P=0.012). After adjusting for potential confounders (body mass index, age at menarche, parity, hypertension, diabetes mellitus, family history of endometrial cancer, hormone replacement therapy, smoking status, and alcohol consumption), the risk of endometrial cancer was significantly lower both in carriers of one variant allele and in carriers of either one or two of the variant alleles (OR=0.47, 95% CI=0.26-0.85, P=0.017; OR=0.50, 95% CI=0.28-0.89, P=0.019; respectively). CONCLUSION: The results suggest that these LTalpha polymorphisms play an important role in the tumorigenesis of endometrial cancer.

Alleles↗

PubMed2006

A polymorphism of C-to-T substitution at -31 IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population.

Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with gastric cancer risk, of which IL1B-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the IL1B transcription. The signal transduction target upon interleukin 1 beta (IL1beta) stimulation, the nuclear factor of kappa B (NFkappaB) activation, supports cancer development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NFkappaB functions on cancer development, we sought to determine if Japanese gastric cancer patients were affected by the IL1B -31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in IL1B in both the cases and controls (R (2)=0.94). Neither IL1B-31, -511 nor FAS-670 polymorphisms showed significantly different risks of gastric adenocarcinoma. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with IL1B-31TT (or IL1B-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either IL1B-31TT (or IL1B-511CC) genotype compared with stage I subjects. These observations suggest that IL1B-31TT and IL1B-511CC are associated with disease progression.

Adenocarcinoma↗

PubMed2006

Meat, milk, saturated fatty acids, the Pro12Ala and C161T polymorphisms of the PPARgamma gene and colorectal cancer risk in Japanese.

The peroxisome proliferator-activated receptor gamma (PPARgamma) gene plays important roles in energy homeostasis. To examine interactions between consumption of foods and fatty acids and the Pro12Ala and C161T (His447His) polymorphisms for colorectal cancer, we performed two case-control studies in Japanese. In study 1, there were 128 colorectal cancer cases and 238 non-cancer controls, and in study 2 there were 257 cases and 771 (age- and sex-matched) non-cancer controls. Assessment of food and nutrients consumption in study 1 was via a nine-item questionnaire, while in study 2 assessment of consumption was according to a more detailed semiquantitative food frequency questionnaire. Consumption of foods and fatty acids was divided into low, moderate and high groups. The overall frequency of the Ala allele was <4%, and the frequencies of the Pro/Pro + C/C and Pro/Pro + (C/T + T/T) genotypes were 70-73% and 20-26%, respectively. Compared with subjects with low meat intake and the Pro/Pro + C/C genotype, those with high meat consumption and the same genotype had a stronger increased risk in study 1 [OR, 2.88; 95% CI, 1.14-7.30; P for trend = 0.02], but a positive association with processed meat consumption was greatest in those with the Pro/Pro + (C/T + T/T) genotype (P for trend = 0.05) in study 2. Likewise, high consumption of saturated fatty acids and milk appeared to confer marginal increased risk and stronger decreased risk, respectively, in those with the Pro/Pro and Pro/Pro + C/C genotypes (OR, 1.35 and 0.65; 95% CI, 0.93-1.96 and 0.43-1.00; P for trend = 0.10 and 0.06). Further large-scale studies are needed to determine colorectal cancer risk according to relationships between the PPARgamma gene polymorphisms and dietary intakes of meat, processed meat, milk and saturated fatty acids in Japanese with very low frequency of the Ala allele.

Adult↗

PubMed2006

Prognostic significance of T-cell or cytotoxic molecules phenotype in classical Hodgkin's lymphoma: a clinicopathologic study.

PURPOSE: Classical Hodgkin's lymphoma (CHL) is characterized by Hodgkin's and Reed-Sternberg (H-RS) cells, most of which are derived from germinal-center B cells. Nevertheless, one or more markers for T cells and follicular dendritic cells (FDC) may be expressed in a minority of H-RS cells in some CHL patients, although the clinical significance of this remains controversial. The aim of this study was to clarify the association between phenotypic expression and clinical outcome in CHL. PATIENTS AND METHODS: Participants were 324 consecutive CHL patients, comprising 132 patients with nodular sclerosis (NS), 35 patients with NS grade 2 (NS2), and 157 patients with mixed cellularity (MC). We evaluated the presenting features and prognosis of patients on categorization into four phenotypically defined groups: B-cell (CD20+ and/or CD79a+; n = 63), T-cell and/or cytotoxic molecules (CD3+, CD4+, CD8+, CD45RO+, TIA-1+, and/or granzyme B+; n = 27), FDC (CD21+ without B-cell marker; n = 22), and null-cell types (n = 212). Other potential prognostic factors were examined. RESULTS: The T-cell and/or cytotoxic molecules group showed a significantly poorer prognosis than the other three groups (P < .0001). This finding was seen consistently in multivariate analyses. Morphologic subtyping (NS/NS2/MC) and Epstein-Barr virus positivity were not identified as independent prognostic factors. CONCLUSION: The presence of T-cell and/or cytotoxic antigens in H-RS cells may represent a poor prognostic factor in CHL, even if their expression is not regarded as lineage specific. Examination of T-cell and/or cytotoxic molecules phenotype in CHL patients is recommended as a routine pathologic practice.

Adolescent↗

PubMed2006

Effect of dietary antioxidants and risk of oral, pharyngeal and laryngeal squamous cell carcinoma according to smoking and drinking habits.

Several intervention trials and prospective studies have reported that beta-carotene supplementation is not associated with a decreased risk of several cancers among smokers and drinkers, and that it may even have adverse effects in these groups. The relationship between dietary antioxidant intake and the risk of head and neck squamous cell carcinoma (HNSCC) has been examined intensively, but little is known about the effects of antioxidants on HNSCC with respect to smoking and drinking habits. Here, we conducted a case-control study of 385 histologically confirmed cases of HNSCC (193 oral, 132 pharyngeal and 60 laryngeal), excluding nasal and paranasal cancer, and 1925 age-matched and sex-matched cancer-free outpatient controls using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center, Japan. The intake of nutrients and food groups was assessed with a food frequency questionnaire, and multivariate-adjusted odds ratios for cancer were estimated for smoking and drinking habits using logistic models. The results showed an overall inverse association between the intake of dietary antioxidants, including carotene, and vitamins C and E, and risk of HNSCC. The protective effect of these antioxidants was seen in both men and women. High consumption of antioxidants was associated with a decreased risk of HNSCC among smokers, drinkers and those with both smoking and drinking habits. These findings suggest that dietary antioxidant intake prevents HNSCC in smokers and drinkers.

Adult↗

PubMed2006

Allogeneic hematopoietic stem cell transplantation as part of postremission therapy improves survival for adult patients with high-risk acute lymphoblastic leukemia: a metaanalysis.

BACKGROUND: The prognosis for adult patients with acute lymphoblastic leukemia (ALL) remains unsatisfactory primarily because of the high incidence of recurrence. Therefore, optimal postremission therapy is a matter of vital concern. In particular, the clinical efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) should be clarified. METHODS: Rigorous criteria were used to select 7 studies of adult ALL that prospectively assessed overall survival (OS) using natural randomization based on donor availability combined with intention-to-treat analyses. The authors then performed a metaanalysis to evaluate the role of allogeneic HSCT. RESULTS: Seven studies that included 1274 patients were selected. A metaanalysis demonstrated that patients in the donor groups had significantly better survival than patients in the no-donor groups (hazard ratio [HR], 1.29; 95% confidence interval [95% CI], 1.02-1.63 [P = .037]). When only high-risk patients were included in the analysis, the superiority of the survival advantage was even greater (HR, 1.42; 95% CI, 1.06-1.90 [P = .019]). A meta-regression analysis revealed that compliance with allogeneic HSCT showed a significant and positive correlation with survival (coefficient, 0.022; P < .01), suggesting that the greater the proportion of patients who actually received allogeneic HSCT, the better the survival of the donor group. No beneficial effects of autologous HSCT were observed. CONCLUSIONS: The current findings demonstrated that allogeneic HSCT improves the outcome of adult patients with high-risk ALL. Although these analyses were based on abstracted data, the results indicated that allogeneic HSCT should be considered for such patients if a suitable donor is available.

Adult↗

PubMed2006

Relationship between epidermal growth factor receptor gene mutations and the severity of adverse events by gefitinib in patients with advanced non-small cell lung cancer.

PURPOSE: Recent reports have demonstrated that mutation of epidermal growth factor receptor (EGFR) gene is predictive factor for tumor responsiveness to gefitinib suggesting the importance of EGFR status for the treatment of the patients with non-small cell lung cancer (NSCLC). However, the relationship between EGFR mutation and adverse events of gefitinib is still unknown. The aim of this study was to evaluate its correlation. PATIENTS AND METHODS: Twenty-six tumor samples from Japanese NSCLC patients who received gefitinib in Okayama University Hospital between November 2000 and October 2004 were examined exons 18-21 of EGFR using direct sequence method. We retrospectively reviewed the clinical records and compared EGFR mutation status with adverse events during gefitinib treatment. RESULTS: Of all 26 patients, EGFR mutation (exon 19 in-frame deletion, 6; exon 21 L858R, 5), were detected in 11 patients (42.3%). The principal adverse event was skin rash (89%), diarrhea (39%), and liver injury (39%). Grade 3 or more adverse events were not common. EGFR mutation status was correlated with neither its frequency nor severity of adverse events during gefitinib treatment including skin rash, diarrhea, liver injury, and interstitial lung disease. As expected, objective response rate of those with EGFR mutations was significantly higher than those without EGFR mutations (78% versus 21%, P<0.001). CONCLUSION: Our study did not demonstrate the presence of close relationships between EGFR mutation status and adverse events during gefitinib treatment.

Adenocarcinoma↗

PubMed2006

Mutational and epigenetic evidence for independent pathways for lung adenocarcinomas arising in smokers and never smokers.

Genetic and epigenetic alterations are considered to play important roles in lung cancer. Recent studies showed that EGFR and K-RAS mutations exhibited a mutually exclusive pattern in adenocarcinoma of the lung, suggesting the presence of two independent oncogenic pathways. However, it is unknown how epigenetic alterations were involved in lung carcinogenesis mediated by EGFR or K-RAS mutation. In this study, we examined the relationship between genetic and epigenetic alterations in 164 cases of lung adenocarcinoma. Somatic mutations were determined by direct sequence of EGFR exons 18 to 21 and K-RAS codons 12 and 13. Methylation status of p16(INK4a), RASSF1A, APC, RARbeta, and CDH13, frequently methylated in lung cancer, was determined by methylation-specific PCR and the degree of methylation was defined as the methylation index. Multivariate analysis adjusted for age, sex, and smoking dose showed that the probability of having EGFR mutation was significantly lower among those with p16(INK4a) and CDH13 methylation than in those without [p16(INK4a): odds ratio (OR), 0.07; 95% confidence interval (95% CI), 0.02-0.33; CDH13: OR, 0.34; 95% CI, 0.15-0.77] and the methylation index was significantly lower in EGFR mutant cases than in wild type (OR, 0.70; 95% CI, 0.52-0.95). By contrast, K-RAS mutation was significantly higher in p16(INK4a) methylated cases than in unmethylated cases (OR, 4.93; 95% CI, 1.54-15.7) and the methylation index was higher in K-RAS mutant cases than in wild type with marginal significance (OR, 1.46; 95% CI, 0.95-2.25). Our results indicate the differences in the evolvement of epigenetic alterations between the EGFR- and K-RAS-mediated tumorigenesis and suggest the specific interaction of genetic and epigenetic changes in tumorigenesis of lung cancer.

Adenocarcinoma↗

PubMed2006

A past history of gastric ulcers and Helicobacter pylori infection increase the risk of gastric malignant lymphoma.

Helicobacter pylori (H. pylori) is a causative agent for peptic ulcers as well as some types of gastric lymphoma; however, the relationship between a peptic ulcer history in combination with H. pylori infection and the risk of gastric lymphoma has not been fully evaluated. To examine this point, we conducted a case-control study with 645 patients histologically diagnosed as having malignant lymphomas and 3225 non-cancer controls. Plasma H. pylori IgG status was assessed for subgroups for which blood samples were available (116 cases and 114 controls). An association with a history of gastric, but not duodenal ulcers was found for gastric lymphoma [odds ratio (OR) = 5.41, 95% confidence interval (CI): 3.12-9.39]. In the examination according to histological subtype, the OR was high for both gastric mucous-associated lymphoid tissue (MALT) lymphoma (OR = 5.54, 95% CI: 2.56-12.01) and diffuse large B-cell lymphoma (DLBCL) (OR = 7.23, 95% CI: 2.62-19.90). In the analysis of H. pylori antibody, the risk of total gastric lymphoma was associated with H. pylori infection (OR = 5.34, 95% CI: 1.42-20.05). A high prevalence of H. pylori infection was also found for both gastric MALT lymphoma (8 out of 10: 80.0%) and DLBCL (8 out of 9: 88.9%). Further, in subgroup analysis of subjects with H. pylori infection, gastric ulcer history, but not duodenal ulcer history was associated with the risk of gastric lymphoma (OR = 4.15, 95% CI: 1.02-16.89). In conclusion, we found a positive association with a past history of gastric ulcer and H. pylori infection for gastric lymphoma, while duodenal ulcer history was no association. These results suggested the risk of gastric lymphoma increased by interaction between H. pylori infection and gastric ulcer history. Further studies are warranted.

Adolescent↗

PubMed2006

Clustered incidence of acute promyelocytic leukemia during gefitinib treatment for non-small-cell lung cancer: experience at a single institution.

Although gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been shown a significant activity for recurrent non-small-cell lung cancer (NSCLC), its long-term adverse effect with its continuous usage has hitherto not been clearly elucidated. Subjects were 108 consecutive NSCLC cases who were treated with gefitinib between November 2001 and December 2004 at our single institution. A crude incidence rate ratio was calculated by ratio of crude incidence rate in our subject to population-based incident rate of all leukemia (ICD: C91-95) in the same region. The 95% confidence intervals (CIs) were calculated based upon a Poisson distribution. Three cases of acute promyelocytic leukemia (APL) occurred during gefitinib treatment, and these patients' past treatment histories are presented herein. No other malignancy was identified. All of the cases were diagnosed at the stage of mild-to-moderate cytopenia, especially thrombocytopenia, without disseminated intravascular coagulation. All presented a normal karyotype with positive PML-RARalpha in RT-PCR, indicating submicroscopic translocation. They responded well to APL treatments, including all-trans-retinoic acid. The crude incident rate ratio was 639.9 (95% confidence interval: 131.6-1,878.9, P < 0.0001) when the APL incidence in this cohort was compared to all leukemia cases in the general population in the same district in Japan. Thus we had three cases of secondary APL patients within the gefitinib-treated NSCLC cohort. Although we cannot exclude an effect of past exposure of other cytotoxic agents and radiotherapy as a cause of APL, APL inducibility of gefitinib should be clarified in the further study.

Adult↗

PubMed2006

Smoking increases the treatment failure for Helicobacter pylori eradication.

PURPOSE: Treatment failure for Helicobacter pylori (H. pylori) eradication is encountered in approximately 10-20% of patients, and many studies have pointed to a link with smoking. To investigate the effects of smoking on eradication outcome, we performed a meta-analysis. METHODS: A PubMed search was performed to retrieve articles published up to August 2005. Pooled odds ratio (OR) and differences rate for H. pylori eradication failure in smokers compared with nonsmokers were used as summary statistics. Meta-regression was used for examining the source of heterogeneity. RESULTS: Twenty-two published studies (5538 patients), which provided information on eradication failure according to smoking status, were included in the analysis. The summary OR for eradication failure among smokers relative to nonsmokers was 1.95 (95% confidence interval [CI]: 1.55-2.45; P <.01). It corresponds with the differences in eradication rates between smokers and nonsmokers (8.4% [95% CI: 3.3-13.5%, P <.01]). Meta-regression analysis demonstrated that a high proportion of nonulcer dyspepsia patients in studies revealed a higher failure rate among smokers, compared with a low proportion of nonulcer dyspepsia. CONCLUSIONS: Our meta-analysis demonstrated that smoking increases the treatment failure rate for H. pylori eradication.

Anti-Bacterial Agents↗

PubMed2006

Advances in our understanding of postoperative adjuvant chemotherapy in resectable non-small-cell lung cancer.

PURPOSE OF REVIEW: After publication in 1995 of a meta-analysis of adjuvant chemotherapy in the treatment of NSCLC, a number of randomized trials investigated adjuvant chemotherapy using more active chemotherapeutic regimens and larger numbers of accrued patients per trial. This review will focus on recent clinical trials for adjuvant chemotherapy, and will help to interpret the applicability of these results to daily clinical practice. RECENT FINDINGS: Four large-scale randomized trials that used platinum-based chemotherapy have reported positive results during the last 3 years. These trials included cisplatin-based chemotherapy [the International Adjuvant Lung Cancer (IALT) trial], cisplatin plus vinorelbine [the National Cancer Institute of Canada (NCIC) BR10 trial], and carboplatin plus paclitaxel [the Cancer and Leukemia Group B (CALGB) 9633 trial]. More recently, another adjuvant trial [Adjuvant Navelbine International Trialist Association (ANITA)] was reported, which has added greatly to our understanding of the potential role of adjuvant treatment. Regarding adjuvant UFT (tegafur and uracil) chemotherapy, an individual patient data-based meta-analysis demonstrated its significant effect on survival in selected patients with completely resected non-small-cell lung cancer. SUMMARY: Recent trials indicate a survival benefit of postoperative adjuvant chemotherapy. These findings are anticipated to change the clinical management of patients with completely resectable non-small-cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with risk of lymphoid malignancies.

It has been speculated that the use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors (statins) is associated with the risk of malignant diseases. Considering their immunosuppressive activities, malignant diseases that are associated with an immunosuppressive status seem feasible to examine the association. We therefore examined the association between statin use and development of lymphoid malignancies in a case-control study. Cases were 221 consecutive incident cases with histopathologically proven lymphoid malignancies (lymphoma and myeloma), hospitalized in the Department of Hematology of Toranomon Hospital (Tokyo, Japan) between 1995 and 2001. Two independent control groups, comprising 442 and 437 inpatients without malignancies from the Departments of Orthopedics and Otorhinolaryngology of the same hospital, were selected to test for consistency of association. Controls were matched individually with cases for age, sex and year of admission. Subject information, including statin use, was abstracted from medical records at the time of hospitalization. Strength of association was evaluated as an adjusted odds ratios (aOR) using a conditional logistic regression model. A higher frequency of statin use was found among patients with lymphoid malignancies in comparison with both orthopedic (aOR 2.11, 95% CI 1.20-3.69, P = 0.009) and otorhinolaryngology patients (aOR 2.59, 95% CI 1.45-4.65, P = 0.001), the significance being maintained when the two control groups were combined (aOR 2.24, 95% CI 1.37-3.66, P = 0.001). In conclusion, we observed an elevated risk of lymphoid malignancy with statin use among Japanese patients. Further evaluations in different populations are required to draw conclusions as to the carcinogenicity of lymphoid malignancies with statin use.

Aged↗

PubMed2006

Transient respiratory disturbance by granulocyte-colony-stimulating factor administration in healthy donors of allogeneic peripheral blood progenitor cell transplantation.

BACKGROUND: Allogeneic peripheral blood progenitor cell (PBPC) transplantation requires granulocyte-colony-stimulating factor (G-CSF) administration to mobilize PBPCs in healthy donors. The effects of G-CSF on pulmonary functions, however, have not been clearly elucidated in PBPC donors. STUDY DESIGN AND METHODS: Respiratory status by measurements of arterial blood gas was prospectively evaluated serially in 25 healthy donors (9 men, 16 women; age, 18-61 years) administered a dose of 10 microg per kg for 5 days. RESULTS: White blood cell (WBC) counts increased in all the subjects after G-CSF administration; means on Days 0, 3, and 5 were 6 x 10(9), 33.4 x 10(9), and 33.6 x 10(9) per L, respectively. The mean PaO(2) values on the respective days were 93.1, 85.8, and 81.8 mmHg, and these changes were significant (p < 0.0001), remaining significant after adjustment for the WBC count. Levels of both PaCO(2) and AaDO(2) were significantly higher after G-CSF administration than those before G-CSF administration (p < 0.0001 and p = 0.0004, respectively). SaO(2) was significantly decreased after G-CSF administration (p = 0.0002). Age was identified as a significant predictive factor for the increase of AaDO(2) and PaO(2) decline. These observations clearly indicate that the gas exchange was significantly affected during G-CSF administration in healthy PBPC donors. CONCLUSION: Considering an increasing use of PBPC mobilization by G-CSF, careful monitoring of the respiratory status is important to ensure safety of PBPC donors, especially elderly donors.

Adolescent↗

PubMed2006

Gene-environment interaction involved in oral carcinogenesis: molecular epidemiological study for metabolic and DNA repair gene polymorphisms.

BACKGROUND: Exposure to environmental carcinogens leads to oral squamous cell carcinoma (OSCC); however, the impact of genetic variations in carcinogen metabolisms and DNA repair on OSCC risk considering environmental exposures has not been clearly elucidated. METHODS: We conducted a case-control study with 122 cases and 241 controls. The risk of OSCC was evaluated in 10 genetic polymorphisms of nine genes, such as CYP1A1, CYP2E1, GSTM1, GSTT1, XPA, XPC, XPC, XPF and ERCC1. Gene-environment interaction was also evaluated. RESULTS: We found that CYP2E1 and XPA polymorphisms significantly affected the OSCC risk. Gene-environment interactions with smoking were significant for CYP2E1 and ERCC1 polymorphisms. Odds ratios for gene-environment interaction were 7.98 (P = 0.036), 9.67 (P = 0.017) and 8.49 (P = 0.031) for CYP2E1RsaI, DraI and ERCC1 polymorphisms, respectively. No interaction was observed with heavy drinking and any polymorphisms. CONCLUSION: CYP2E1, XPA and ERCC1 polymorphisms may affect the risk of OSCC.

Alcohol Drinking↗

PubMed2006

Alcohol dehydrogenase 2 His47Arg polymorphism influences drinking habit independently of aldehyde dehydrogenase 2 Glu487Lys polymorphism: analysis of 2,299 Japanese subjects.

Although the functional effect of alcohol dehydrogenase 2 (ADH2) His(47)Arg polymorphism has been elucidated, its effect on habitual drinking remains unknown. Here, we conducted a cross-sectional study in 2,299 nonalcoholic Japanese subjects (989 men and 1,310 women). Drinking status, ethanol consumption, and physical reaction to one glass of beer were examined with regard to ADH2 and aldehyde dehydrogenase 2 (ALDH2) polymorphism. Strength of associations were assessed by age-, sex-, smoking status-, and genotype-adjusted odds ratios and their 95% confidence intervals. ADH2 His/Arg and Arg/Arg genotypes showed higher risk for habitual drinking. Among men, ALDH2 genotype- and confounder-adjusted odds ratios (95% confidence intervals) were 1.30 (0.89-1.89) and 3.16 (1.03-9.70), and this trend was significant (P = 0.024). A similar trend was observed among women. The combination genotypes of two polymorphisms revealed the clear effect of the ADH2 Arg allele among those with ALDH2 Glu/Lys in both sexes (P(trend) = 0.007 for men and 0.024 for women). Physical reactions, such as flushing and palpitation, were significantly less common in those with Arg/Arg compared with other ADH2 genotypes, and this was marked when combined with ALDH2 Glu/Lys. Heavy drinker status was also strongly associated with ADH2 Arg alleles. In conclusion, this study showed the strong effect of ADH2 His(47)Arg polymorphism on habitual drinking regardless of ALDH2 genotype.

Adult↗