Motoki Iwasaki

University of Alberta, Edmonton, Alberta, Canada

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Publications (234)978.24 Total impact

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    ABSTRACT: Reactive oxygen species (ROS) is a term used to describe a number of reactive molecules and free radicals derived from molecular oxygen [1]. ROS are produced in normal biological processes in cells by means of either enzymatic or nonenzymatic mechanisms and play beneficial and adverse roles in an organism [2]. Oxidative stress, an imbalance toward the pro-oxidative state, is caused by the presence of free radicals or radical-generating agents in concentrations that overwhelm natural radical-blocking or radical-scavenging mechanisms [1]. Under oxidative stress conditions, excessive ROS can damage DNA, cellular proteins, and lipids, leading to fatal lesions in cells that contribute to carcinogenesis [3].The ROS include superoxide, hydrogen peroxide, hydroxyl radical, hydroxyl ion, and nitric oxide [1]. Helicobacter pylori infection was regarded as a human gastric carcinogen by the International Agency for Research on Cancer, and the ROS level was higher in H. pylori-positive than in H. p ...
    European Journal of Epidemiology 04/2015; DOI:10.1007/s10654-015-0025-6 · 5.15 Impact Factor
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    ABSTRACT: Background and Purpose: We examined the association between green tea consumption and mortality due to all causes, cancer, heart disease, cerebrovascular disease, respiratory disease, injuries and other causes of death in a large-scale population-based cohort study in Japan. Methods We studied 90,914 Japanese (aged between 40 and 69 years) recruited between 1990 and 1994. After 18.7 years of follow-up, 12,874 deaths were reported. The association between green tea consumption and risk of all causes and major causes of mortality was assessed using the Cox proportional hazards regression model with adjustment for potential confounders. Results Hazard ratios for all-cause mortality among men who consumed green tea compared with those who drank less than 1 cup per day were 0.96 (0.89 to 1.03) for 1 to 2 cups per day, 0.88 (0.82 to 0.95) for 3 to 4 cups per day, and 0.87 (0.81 to 0.94) for more than 5 cups per day (p for trend <0.001). Corresponding hazard ratios for women were 0.90 (0.81 to 1.00), 0.87 (0.79 to 0.96), and 0.83 (0.75 to 0.91) (p for trend <0.001). Green tea was inversely associated with mortality from heart disease in both men and women, and mortality from cerebrovascular disease and respiratory disease in men. No association was found between green tea and total cancer mortality. Conclusion This prospective study suggests that the consumption of green tea may reduce the risk of all-cause mortality and the three leading causes of death in Japan.
    Annals of Epidemiology 03/2015; 25(7). DOI:10.1016/j.annepidem.2015.03.007 · 2.15 Impact Factor
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    ABSTRACT: To date, the association between diabetes mellitus (DM) and gastric cancer has been controversial, including the underlying mechanism. We investigated the association between plasma diabetic biomarkers (insulin, C-peptide, and blood glucose) and gastric cancer risk. In addition, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were calculated. A total of 36,745 subjects aged 40–69 years in the Japan Public Health Center–based prospective study (JPHC) who returned the baseline questionnaire and provided blood samples were followed from 1990 to 2004. In the present analysis, 477 cases and 477 matched controls were used. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for developing gastric cancer were calculated using conditional logistic regression models. Plasma insulin was positively associated with increased risk of gastric cancer; compared to tertile 1, ORs were 1.69 (95% CI = 1.11–2.59) and 2.01 (1.19–3.38) for tertiles 2 and 3, respectively (p for trend = 0.009). In men, C-peptide was also positively associated with a significant risk; corresponding ORs were 1.42 (0.85–2.38) and 1.91 (1.03–3.54), respectively (p for trend = 0.04). These findings were confirmed for blood samples from the fasting group (≥8 h after a meal). Higher HOMA-IR was also associated with increased risk, whereas no association was observed for blood glucose. Our findings suggest that Japanese population with higher insulin and C-peptide levels derived from insulin resistance have an elevated risk of gastric cancer. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 03/2015; 136(6). DOI:10.1002/ijc.29098 · 5.01 Impact Factor
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    ABSTRACT: Background: Despite the rising consumption of coffee worldwide, few prospective cohort studies assessed the association of coffee intake with mortality including total and major causes of death. Objective: We aimed to investigate the association between habitual coffee drinking and mortality from all causes, cancer, heart disease, cerebrovascular disease, respiratory disease, injuries, and other causes of death in a large-scale, population-based cohort study in Japan. Design: We studied 90,914 Japanese persons aged between 40 and 69 y without a history of cancer, cerebrovascular disease, or ischemic heart disease at the time of the baseline study. Subjects were followed up for an average of 18.7 y, during which 12,874 total deaths were reported. The association between coffee intake and risk of total and cause-specific mortality was assessed by using a Cox proportional hazards regression model with adjustment for potential confounders. Results: We showed an inverse association between coffee intake and total mortality in both men and women. HRs (95% CIs) for total death in subjects who consumed coffee compared with those who never drank coffee were 0.91 (0.86–0.95) for <1 cup/d, 0.85 (0.81–0.90) for 1–2 cups/d, 0.76 (0.70–0.83) for 3–4 cups/d, and 0.85 (0.75–0.98) for >5 cups/d (P-trend < 0.001). Coffee was inversely associated with mortality from heart disease, cerebrovascular disease, and respiratory disease. Conclusion: With this prospective study, we suggest that the habitual intake of coffee is associated with lower risk of total mortality and 3 leading causes of death in Japan.
    American Journal of Clinical Nutrition 03/2015; 101(5). DOI:10.3945/ajcn.114.104273 · 6.92 Impact Factor
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    ABSTRACT: Although various factors thought to be correlated with anxiety in cancer patients, relative importance of each factors were unknown. We tested our hypothesis that personality traits and coping styles explain anxiety in lung cancer patients to a greater extent than other factors. A total of 1334 consecutively recruited lung cancer patients were selected, and data on cancer-related variables, demographic characteristics, health behaviors, physical symptoms and psychological factors consisting of personality traits and coping styles were obtained. The participants were divided into groups with or without a significant anxiety using the Hospital Anxiety and Depression Scale-Anxiety, and a binary logistic regression analysis was used to identify factors correlated with significant anxiety using a multivariate model. Among the recruited patients, 440 (33.0%) had significant anxiety. The binary logistic regression analysis revealed a coefficient of determination (overall R(2)) of 39.0%, and the explanation for psychological factors was much higher (30.7%) than those for cancer-related variables (1.1%), demographic characteristics (2.1%), health behaviors (0.8%) and physical symptoms (4.3%). Four specific factors remained significant in a multivariate model. A neurotic personality trait, a coping style of helplessness/hopelessness, and a female sex were positively correlated with significant anxiety, while a coping style of fatalism was negatively correlated. Our hypothesis was supported, and anxiety was strongly linked with personality trait and coping style. As a clinical implication, the use of screening instruments to identify these factors and intervention for psychological crisis may be needed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Japanese Journal of Clinical Oncology 03/2015; 45(5). DOI:10.1093/jjco/hyv024 · 1.75 Impact Factor
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    ABSTRACT: Previous studies of Japanese migrants have suggested that the increase in colorectal cancer rates occurring after migration is slower among Japanese Brazilians than among Japanese Americans. We hypothesized that this difference may partly reflect differences in vegetable and fruit intake between the populations. Using data from validation studies of food frequency questionnaires being used in comparative case-control studies of colorectal adenoma in Tokyo, São Paulo, and Hawaii, plasma carotenoid, retinol, tocopherol, and coenzyme Q10 levels were measured by high-performance liquid chromatography, and 25-hydroxy vitamin D levels were estimated by enzyme-linked immunosorbent assay. Plasma levels were compared by analysis of covariance between 142 Japanese in Tokyo, 79 Japanese Brazilians in São Paulo, and 78 Japanese Americans in Hawaii. Overall, we found significantly lower plasma carotenoid levels, except for lycopene levels, and retinol levels in Japanese Americans compared with Japanese in Tokyo and Japanese Brazilians. The plasma total carotenoid level was highest in Japanese Brazilians. Compared with the mean level among Japanese Brazilians (1741.2 ng/ml), P for difference was 0.03 among Japanese in Tokyo (1514.4 ng/ml) and less than 0.01 for Japanese Americans (1257.7 ng/ml). Plasma lycopene and tocopherol levels did not substantially differ between the three populations. We also found significantly lower plasma levels of 25-hydroxy vitamin D and total coenzyme Q10 in Japanese in Tokyo than in Japanese Americans and Japanese Brazilians. Higher levels of plasma carotenoids among Japanese Brazilians than among Japanese in Tokyo and Hawaii may have contributed to the slower pace of the increase in colorectal cancer rates observed in that population after migration.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 03/2015; 24(2):155-61. DOI:10.1097/CEJ.0000000000000136 · 2.76 Impact Factor
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    Motoki Iwasaki
    Journal of Epidemiology 02/2015; 25(2):89-90. DOI:10.2188/jea.JE20140269 · 2.86 Impact Factor
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    ABSTRACT: Background: While several studies have provided support for a positive association between meat intake and colorectal neoplasia, the role of heterocyclic amines (HCA), which is hypothesized to underline this relation, has been less consistent. We evaluated the association of HCA intake with colorectal adenoma (CRA) risk in a case-control study in a middle-aged Japanese population. Methods: Study subjects were 738 patients with adenoma and 697 controls who underwent total colonoscopy between 2004 and 2005 and responded to a self-administered lifestyle and dietary questionnaires. HCA exposure concentration was estimated from meat and fish intake based on an HCA database which was validated against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) values measured in human hair. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for the association between HCA and CRA risk after adjusting for potential confounders. Results: High intake of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and total HCA was associated with an increased risk of CRA in women but not in men. The multivariate-adjusted OR for the highest versus lowest quartile in women was 2.10 (95% CI 1.20-3.67, Ptrend=0.01) for MeIQ and 1.73 (95% CI 0.99-3.01, Ptrend=0.03) for total HCA. No clear association with PhIP or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) estimates and no effect modification by NAT2 acetylation genotype was observed. Conclusions: This study suggests that high MeIQ and total HCA estimates are positively associated with CRA risk. Impact: The findings add to evidence that HCA may play a role in colorectal carcinogenesis in humans. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 01/2015; DOI:10.1158/1055-9965.EPI-14-1051 · 4.32 Impact Factor
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    ABSTRACT: Dietary fiber may reduce the risk of prostate cancer, possibly by increasing circulating concentrations of sex hormone-binding globulin and improving insulin sensitivity. However, results from previous epidemiologic studies of fiber intake and prostate cancer are inconsistent, and to our knowledge, no study has comprehensively evaluated the effects of soluble and insoluble fiber on prostate cancer in Asia. The objective was to examine the association between fiber intake and prostate cancer in Japanese men. We conducted a population-based prospective study in 43,435 Japanese men aged 45-74 y. Participants responded to a validated questionnaire, which included 138 food items. Follow-up was from 1995 through 2009. HRs and 95% CIs of incidence were calculated according to quartiles of fiber intake. During the 11.6-y follow-up, of the 825 men newly diagnosed with prostate cancer, 213 had advanced-stage cancer, 582 had organ-localized disease, and 30 had an undetermined stage of disease. Among them, 217 cases were detected by subjective symptoms. Total fiber was not associated with total or advanced prostate cancer, with respective multivariable HRs for the highest and lowest quartiles of 1.00 (95% CI: 0.77, 1.29; P-trend = 0.97) and 0.67 (95% CI: 0.42, 1.07; P-trend = 0.30). Total fiber and insoluble fiber intake were associated with a decreased risk of advanced cancers detected by subjective symptoms, with multivariate HRs (95% CIs) across increasing quartiles of 1.00, 0.58, 0.62, and 0.44 (0.21, 0.92; P-trend = 0.05) for total fiber and 1.00, 0.60, 0.52, and 0.46 (0.22, 0.93; P-trend = 0.04) for insoluble fiber. Soluble fiber intake showed no association with prostate cancer. Dietary fiber is inversely associated with advanced prostate cancer detected by subjective symptoms even among populations with relatively low intake, such as Japanese. These results suggest that a very low intake of dietary fiber is associated with an increased risk of prostate cancer. © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 01/2015; 101(1):118-25. DOI:10.3945/ajcn.114.089581 · 6.92 Impact Factor
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    ABSTRACT: Background: Evidence suggests that estrogen plays a preventive role in primary liver cancer development, and it might be thought that isoflavones, which are structurally similar to estrogens and bind to estrogen receptors, are associated with the risk of liver cancer. We investigated this suspected association by measuring plasma concentrations of isoflavones in a nested case-control study of a population-based prospective cohort in Japan. Methods: From 18,628 target participants aged 40 to 69 years who returned the baseline questionnaire and provided blood samples, we selected those with either hepatitis B or hepatitis C virus infection at baseline (n=1,544). Among these, 90 (28 women and 62 men) were newly diagnosed with primary liver cancer from 1993 through 2006; they were matched with 175 controls (54 women and 121 men). Plasma concentrations of isoflavones (genistein, daidzein, glycitein, and equol) were measured using triple quadrupole tandem liquid chromatography-mass spectrometry. The odds ratios of liver cancer development based on plasma concentrations were estimated with a conditional logistic regression model. Results: Basically, distributions of plasma isoflavone concentrations did not differ between the cases and controls. No statistically significant associations of genistein, daidzein, glycitein, and equol with primary liver cancer risk were found in either women or men. Conclusions: In middle-aged Japanese women and men with hepatitis virus infection, plasma isoflavones were unassociated with the occurrence of primary liver cancer. Impact: The role of isoflavones in liver carcinogenesis merits further study using both biomarkers and data on dietary intake of isoflavones. Copyright © 2014, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 12/2014; DOI:10.1158/1055-9965.EPI-14-1118 · 4.32 Impact Factor
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    ABSTRACT: The aim of the study was to investigate trends in cancer prognosis by examining the relationship between period of diagnosis and probability of death from cancer in a population-based cohort. Within a cohort of Japanese men and women aged 40-69 years and free of prior diagnosis of cancer and cardiovascular disease at baseline, data from 4403 patients diagnosed with cancer between 1990 and 2006 and followed up until 2012 were analyzed using survival regression models to assess the presence of an effect of the period of diagnosis (before 1998 versus after 1998) on the risk of dying from cancer. We noted a significant decrease in risk of dying from cancer among individuals diagnosed after 1998 with lung cancer (hazard ratio [HR]=0.676 [0.571-0.800]) or colorectal cancer (HR=0.801 [0.661-0.970]). A decrease in the estimated five-year probability of death from cancer was also noted between the first (before 1998) and the second (after 1998) period of diagnosis for lung and colorectal cancers (e.g., 85.4% vs. 73.3% for lung cancer and 44.6% vs. 37.7% for colorectal cancer, respectively, for stage III in men aged 60 at diagnosis). This study presented the first scientific evidence of improvement in prognosis for lung and colorectal cancer patients in a population-based cohort in Japan. Our results suggest that recent advances in cancer treatment could have influenced cancer survival differently among lung, colorectal and gastric cancers. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Cancer Epidemiology 12/2014; 39(1). DOI:10.1016/j.canep.2014.11.008 · 2.56 Impact Factor
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    ABSTRACT: The association between alcohol consumption, genetic polymorphisms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), and gastric cancer risk is not completely understood. We investigated the association between genetic polymorphisms ADH1B (rs1229984), ADH1C (rs698), and ALDH2 (rs671), alcohol consumption, and the risk of gastric cancer among Japanese subjects in a population-based, nested, case-control study (1990-2004). Among 36 745 subjects who answered the baseline questionnaire and provided blood samples, 457 new gastric cancer cases matched to 457 controls were used in the analysis. The odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using logistic regression models. No association was observed between alcohol consumption, ADH1B (rs1229984), ADH1C (rs698), and ALDH2 (rs671) polymorphisms, and gastric cancer risk. However, considering gene-environmental interaction, ADH1C G allele carriers who drink ≥150 g/week of ethanol had a 2.5-fold increased risk of gastric cancer (OR = 2.54, 95% CI = 1.05-6.17) relative to AA genotype carriers who drink 0 to <150 g/week (P for interaction = 0.02). ALDH2 A allele carriers who drink ≥150 g/week also had an associated increased risk (OR = 2.08, 95% CI = 1.05-4.12) relative to GG genotype carriers who drink 0 to < 150 g/week (P for interaction = 0.08). To find the relation between alcohol consumption and gastric cancer risk, it is important to consider both alcohol consumption level and ADH1C and ALDH2 polymorphisms. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Carcinogenesis 12/2014; 36(2). DOI:10.1093/carcin/bgu244 · 5.27 Impact Factor
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    ABSTRACT: Non-participants to psychosocial studies have been shown to have higher mortality, and mortality differs between partial and complete responders to psychosocial questionnaires. Yet, there is very little information available directly linking survey response status with completing suicide. The study population consisted of the participants of the Japanese Public Health Center-based prospective study. Ninety-nine thousand four hundred thirty-nine subjects who returned the 10-year follow-up questionnaire and 31 754 individuals who did not return the questionnaire were included in our analyses. The risk of dying by suicide according to response status was estimated by Cox regression models. There were 358 suicides during 1 128 831 person-years of follow-up (mean follow-up time: 8.6 years). Of those who returned the questionnaire, 53.9% were full responders, 42.8% were partial non-responders, and 3.3% were complete non-responders. The risk of suicide was increased for both complete non-responders [hazard ratio (HR) = 1.84, 95% confidence interval (CI), 0.51, 6.64] and partial non-responders (HR = 1.36, 95% CI, 0.999, 1.84) to the questionnaire as a whole. The adjusting variables explained around 40% of the risk for complete non-responders whereas they did not explain the increased risk of suicide for partial non-responders. The risk of dying by suicide was significantly increased for partial non-responders to the subscale on coping (HR = 1.36, 95% CI, 1.01, 1.85) and for complete non-responders to questions on sleep (HR = 2.07, 95% CI, 1.03, 4.16). Partial and complete non-responders have increased suicide risk compared with full responders. More than one non-responder category should therefore be considered when interpreting data pertaining to psychosocial questionnaires in longitudinal studies. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
    The European Journal of Public Health 12/2014; DOI:10.1093/eurpub/cku209 · 2.46 Impact Factor
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    ABSTRACT: Coffee is a commonly consumed beverage which contains several potential anticarcinogenic and chemopreventive compounds, and has been hypothesized to have protective effects in colorectal neoplasia. However, the limited available data on coffee consumption in relation to colorectal adenoma (CRA), a precursor lesion to most colorectal cancers, remain largely inconsistent. In this study, we evaluated the association of coffee intake with the risk of CRA in a middle-aged Japanese population. Study subjects were selected from examinees who underwent total colonoscopy as part of a cancer screening program and responded to self-administered dietary and lifestyle questionnaires. A total of 738 patients with adenoma and 697 controls were included in the study. Coffee intake was assessed with a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) of CRA, with adjustment for potential confounding factors. High coffee consumption was associated with a reduced risk of CRA, with a multivariate-adjusted OR for the highest versus lowest quartile of coffee intake of 0.67 (95% CI=0.48–0.93; Ptrend=0.02). The inverse association of coffee intake was limited to proximal (OR=0.64; 95%CI= 0.44–0.95; Ptrend=0.04) and distal colon adenoma (OR=0.62; 95%CI=0.39–0.99; Ptrend=0.06), and appeared to be more evident with small (OR=0.68; 95%CI=0.49–0.96; Ptrend=0.04) and single adenomas (OR=0.65; 95%CI=0.44–0.95; Ptrend=0.02). Green tea intake was not found to be associated with CRA risk. This study provides support for the protective effect of coffee drinking on colon adenomas, a precursor of colon cancer. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 12/2014; 137(2). DOI:10.1002/ijc.29390 · 5.01 Impact Factor
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    ABSTRACT: The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P<5 × 10(-8)) in 16,823 cases and 18,211 controls of European ancestry. This study reveals a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.4 × 10(-9)), providing additional insight into the aetiology of CRC and highlighting the value of association mapping in diverse populations.
    Nature Communications 10/2014; 5(19 Supplement):4613. DOI:10.1158/1538-7445.AM2014-LB-282 · 10.74 Impact Factor
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    ABSTRACT: Background: In many developed countries, socioeconomic status is associated with cancer incidence and survival. However, research in Japan is sparse. We examined the association between neighborhood deprivation based on the Japanese Deprivation Index and the risk of incidence, mortality and survival from total and major cancers in the Japan Public Health Center-based Prospective Study. Methods: 86,112 participants were followed through the end of 2009. A total of 10,416 incident cases and 5,510 deaths from cancer were identified among 1,348,437 person-years of follow-up (mean follow-up: 15.7 years). The Japanese deprivation index was used to access neighborhood deprivation. Hazard ratios and 95% confidence intervals were calculated by Cox regression analysis. Results: We found no associations between neighborhood deprivation index and the incidence of total and major cancers. In some cancer risks or deaths, however, we found positive or inverse associations with a higher deprivation index, such as a decreased risk of colorectal cancer incidence and an increased risk of liver cancer incidence and deaths in women. Conclusion: Although some positive or inverse associations were detected for specific sites, the neighborhood deprivation index has no substantial overall association with the risk of incidence, mortality and survival from cancer in the Japanese population.
    PLoS ONE 09/2014; 9(9):e106729. DOI:10.1371/journal.pone.0106729 · 3.53 Impact Factor
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    ABSTRACT: Objective There have been very few population-based prospective studies that have investigated the risks of deaths by suicide and other externally caused injuries (ECIs) among cancer patients in an Asian population. This study investigated whether the risk of death by both suicide and ECIs increases during the first year following the initial diagnosis of cancer.Methods Data were analyzed from a population-based cohort of Japanese residents between 1990 and 2010, collected during the Japan Public Health Center-based Prospective Study. Poisson regression models were used to calculate adjusted risk ratios (RRs) for both suicide and ECI deaths. To adjust for unmeasured confounding factors, case-crossover analyses were conducted for all patients with cancer who died by suicide and ECIs.ResultsA population-based cohort of 102,843 Japanese residents was established. During the follow-up period, there were 34 suicides and 48 ECI deaths among patients with cancer, as compared with 527 suicides and 707 ECI deaths among those who did not have cancer. Analyses revealed that those who were newly diagnosed with cancer were at a greatly increased risk of death by suicide and ECIs within the first year after their diagnosis (suicide RR = 23.9, 95% CI: 13.8–41.6; ECI RR = 18.8, 95% CI: 11.4–31.0). Furthermore, the case-crossover analyses generally confirmed the results of the Poisson regressions.Conclusions The risks of suicide and ECI deaths within the first year after a cancer diagnosis were higher than those among cancer-free populations. A diagnosis of cancer is a critical experience that may increase the risk of fatal outcomes. Copyright © 2014 John Wiley & Sons, Ltd.
    Psycho-Oncology 09/2014; 23(9). DOI:10.1002/pon.3529 · 4.04 Impact Factor
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    ABSTRACT: In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,8 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4950 at q32. (in intron 2 of the ZC3H11A gene; P = 8.82 × 0 −9), rs0474352 at 5q4.3 (near the ARRDC3 gene; P = .67 × 0 −9) and rs2290203 at 5q26. (in intron 4 of the PRC1 gene; P = 4.25 × 0 −8). We replicated these associations in 6,003 cases and 4,335 controls of European ancestry (P = 0.030, 0.004 and 0.00, respectively). Data from the ENCODE Project suggest that variants rs4950 and rs0474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer. Breast cancer is one of the most common malignancies among women worldwide. Genetic factors have a substantial role in breast cancer etiology 1,2 . Thus far, genome-wide association studies (GWAS) have identified approximately 75 genetic loci associated with breast cancer risk 2–5 . With the exception of the studies we have conducted among East Asian women 6–9 and one study conducted among women of African ancestry 10 , all other published GWAS have been conducted among women of European ancestry. Genetic risk variants identified thus far from GWAS explain only about 10% of familial risk for breast cancer in East Asian women 3 . Given the dif-ferences in genetic architecture and environmental exposures for women of European and East Asian ancestry, additional GWAS need to be conducted among East Asian women to study the genetic basis of breast cancer risk. The current study was conducted as part of the Asia Breast Cancer Consortium (ABCC) to search for additional susceptibility loci for breast cancer. Included in this study are data obtained from 22,780 breast cancer cases and 24,181 controls who were recruited in 14 studies conducted in multiple Asian countries (Supplementary Table 1). The discovery stage (stage 1) included 2 GWAS in which 5,285 Chinese women (SBCGS-1) and 4,777 Korean women (SeBCS1) were scanned primarily using Affymetrix Genome-Wide Human SNP Array 6.0, which consists of 906,602 SNPs. After applying quality control filters described previously 6,9,11 , 5,152 Chinese women (2,867 cases and 2,285 controls; 677,157 SNPs) and 4,298 Korean women (2,246 cases and 2,052 controls; 555,117 SNPs) remained in the cur-rent analysis. Imputation was conducted for each study following the MACH algorithm 12 using HapMap 2 release 22 CHB (Han Chinese in Beijing, China) and JPT (Japanese in Tokyo, Japan) data (2,416,663 SNPs) as the reference. Only SNPs with a high imputation quality score (RSQR ≥ 0.50) were analyzed for associations with breast can-cer risk. In the analyses of data from Chinese and Korean women, a total of 1,930,412 and 1,907,146 SNPs, respectively, were included. A meta-analysis of these GWAS data was conducted using a fixed-effects, inverse variance meta-analysis with the METAL program 13 . There was little evidence of inflation in the association test statis-tics for the studies included in stage 1 (genomic inflation factors (λ): λ = 1.0426 for SBCGS-1, λ = 1.0431 for SeBCS1 and λ = 1.0499 for both studies combined; Supplementary Fig. 1). When scaled to a study of 1,000 cases and 1,000 controls, λ 1,000 values were 1.02, 1.02 and 1.01, respectively. To select SNPs for stage 2 replication, we used the following criteria: (i) association P < 0.05 in the stage 1 meta-analysis results; (ii) the
    Nature Genetics 07/2014; DOI:10.1038/ng.3041 · 29.65 Impact Factor
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    Japanese Journal of Clinical Oncology 06/2014; 44(7):641-650. DOI:10.1093/jjco/hyu061 · 1.75 Impact Factor
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    ABSTRACT: No large population-based prospective study has investigated the risks of suicide and death by other externally caused injuries (ECIs) among stroke patients. The purpose of this study was to examine whether stroke increases the risks of suicide and ECI deaths.

Publication Stats

4k Citations
978.24 Total Impact Points

Institutions

  • 2015
    • University of Alberta
      Edmonton, Alberta, Canada
  • 2003–2015
    • National Cancer Center, Japan
      • Research Center for Cancer Prevention and Screening
      Edo, Tōkyō, Japan
  • 2012
    • Osaka City University
      • Department of Public Health
      Ōsaka, Ōsaka, Japan
    • Tokyo University of Agriculture
      • Department of Nutrition
      Edo, Tōkyō, Japan
  • 2011–2012
    • Vanderbilt University
      • Division of Epidemiology
      Nashville, MI, United States
  • 2010
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 2007
    • Tokyo University and Graduate School of Social Welfare
      Edo, Tōkyō, Japan
    • Miyazaki University
      • Department of Obstetrics and Gynecology
      Миядзаки, Miyazaki, Japan
  • 2006
    • Nagoya City University
      Nagoya, Aichi, Japan
  • 2003–2004
    • National Cancer Research Institute
      Londinium, England, United Kingdom
  • 2002
    • Gunma University
      • Department of Public Health
      Maebashi, Gunma Prefecture, Japan