Background: High-sensitivity C-reactive protein (hs-CRP) is a commonly used inflammatory marker. The association between hs-CRP and cancer is less consistent than that between hs-CRP and cardiovascular diseases. This study explored the association between hs-CRP and cancer, using a large database of Korean health examination records.
Methods: A total of 80 781 Koreans who visited the health promotion center of a general hospital were included. There were 729 cases of cancer of any primary site during a 3-year period. Subjects with a known cancer or a condition capable of affecting hs-CRP were excluded.
Results: Serum hs-CRP was significantly higher in cancer cases (2.9 mg/L) than in non-cases (1.4 mg/L; P < 0.0001). With the lowest hs-CRP category (<1 mg/L) as reference, the crude odds ratios (ORs) for cancer were 1.36 (95% confidence interval [CI] = 1.16–1.62) for the second highest category (1–3 mg/L) and 2.49 (95% CI = 2.02–3.07) for the highest category (>3 mg/L), and the adjusted ORs for cancer were 1.16 (95% CI = 0.95–1.42) for the second highest category and 1.94 (95% CI = 1.51–2.51) for the highest category. After excluding cancer cases detected within 1 year after the check-up, the associations remained, although the reduced number of cancer cases (n = 88) attenuated the significance of the associations.
Conclusions: Serum hs-CRP was positively associated with the risk of cancer, although causality cannot be inferred in this cross-sectional study. The results support the hypothesis that chronic inflammation plays a role in cancer.

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Background: It has been reported that fruit intake protects against cardiovascular disease (CVD). However, most of the relevant studies were conducted in Western countries, and only a few investigated Japanese populations. The present cohort study assessed the effect of citrus fruit intake on the incidence of CVD and its subtypes in a Japanese population.
Methods: A baseline examination consisting of physical and blood examinations and a self-administered questionnaire was conducted during the period from April 1992 through July 1995. Dietary habits were assessed using a food frequency questionnaire that was divided into 5 categories. Citrus fruit was examined separately due to its frequent consumption by the general Japanese population. Using the Cox proportional hazards model, data from 10 623 participants (4147 men, 6476 women) who had no history of CVD or carcinoma were analyzed to assess the association between frequency of citrus fruit intake and CVD incidence.
Results: Frequent intake of citrus fruit was associated with a lower incidence of CVD: the hazard ratio for almost daily intake versus infrequent intake of citrus fruit was 0.57 (95% confidence interval: 0.33–1.01, P for trend = 0.04) in men and 0.51 (0.29–0.88, P for trend = 0.02) in women. Frequent intake of citrus fruit was also associated with lower incidences of both all stroke and cerebral infarction, but not hemorrhagic stroke or myocardial infarction.
Conclusions: Frequent intake of citrus fruit may reduce the incidence of CVD, especially cerebral infarction, in men and women.

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Background: Few studies have examined whether declines over time in hand-grip strength (HGS) and fast walking speed (FWS) differ by sex and age among non-Western community-dwelling older adults. This study aimed to quantify changes in HGS and FWS over the 6-year period from 1994 to 2000 and examine whether these changes differed by sex and baseline age among older individuals in a Japanese community.
Methods: We conducted a community-based prospective cohort study. The participants were 513 nondisabled men and women aged 67 to 91 years at the 1994 survey. Independent variables regarding time since baseline, in addition to various time-dependent and time-independent covariates, were obtained in 1994, 1996, 1998, and 2000. The outcome variables were HGS and FWS assessed at each survey. All data on independent and dependent variables that were collected at each survey were simultaneously analyzed using a linear mixed-effects model.
Results: The linear mixed-effects model revealed significant declines in both HGS (−0.70 kg/year, P < 0.001) and FWS (−0.027 m/sec/year, P < 0.001) among nondisabled older participants who had analyzable data in any survey during the 6-year period. Sex was significantly associated with the rate of decline in HGS (P < 0.001), but not FWS (P = 0.211).
Conclusions: In this analysis of nondisabled older Japanese, a mixed-effects model confirmed a significant effect of aging on declines in HGS and FWS and showed that men had a significantly steeper decline in HGS than did women during a 6-year period.

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Background: Although knee pain is common in older persons and can cause ambulatory limitation, its impact on self-reliance has rarely been examined in Japan, particularly in a community setting. The aim of this 3-year cohort study was to investigate the association of knee pain with dependence in activities of daily living (ADL) and mortality in community-dwelling older Japanese adults.
Methods: In 2005, presence of knee pain was assessed by a home visit survey of 1391 older adults aged 65 years or older (participation proportion = 97.3%). A total of 1265 participants who were ADL-independent at baseline were followed for 3 years, and information on outcomes, namely death and dependence in ADL, was collected.
Results: Participants who always had knee pain were more likely to become dependent in ADL than those who reported no knee pain (multivariate-adjusted OR, 1.98; 95% CI, 1.03–3.83); however, always having knee pain was not associated with mortality or a composite outcome of ADL dependence and death. Further analyses of each component of ADL dependence revealed that knee pain was associated with a need for assistance at home (long-term care eligibility, bathing, dressing, and transferring), but not with institutionalization.
Conclusions: The participants were highly representative of the target population and the rate of follow-up was almost perfect (99.4%). The results suggest that knee pain is associated with future dependence in ADL, particularly a need for assistance at home.

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Background: School-based screening and prevention programs for adiposity generally target school children in grades 4 and 6 (age 9–11 years). The aims of this study were to evaluate the validity of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) in identifying abdominal adiposity in fifth-grade Japanese school children and to determine optimal cut-off values for anthropometric measures.
Methods: The target population was fifth-grade school children enrolled in 2 schools in Shizuoka, Japan between 2008 and 2010; 422 of the 466 children participated in the present study. Abdominal adiposity was defined as percent trunk fat in the 95th percentile or higher, as determined by dual-energy x-ray absorptiometry (DXA). We analyzed the validity of BMI, WC, and WHtR using receiver operating characteristic (ROC) curve analysis. The Youden index was used to determine cut-off values of BMI, WC, and WHtR that identify excess abdominal fat.
Results: Optimal cut-off values to identify abdominal adiposity were 20.8 kg/m² (BMI), 76.5 cm (WC), and 0.519 (WHtR) for boys, and 19.6 kg/m² (BMI), 73.0 cm (WC), and 0.499 (WHtR) for girls. Areas under the ROC curve were 0.983 (BMI), 0.987 (WC), and 0.981 (WHtR) for boys, and 0.981 (BMI), 0986 (WC), and 0.992 (WHtR) for girls.
Conclusions: BMI, WC, and WHtR successfully identified a high proportion of children with excess abdominal fat as measured by DXA, demonstrating that these measures are useful indices for school screening.

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Background: Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) are 3 types of skin cancer that have distinct biologic characteristics and prognoses. We evaluated phenotypic differences in the risk of these cancers in US women.
Methods: We conducted a prospective study of 113 139 female nurses from 1984 to 2002. Over the 18 years of follow-up, there were 375 cases of melanoma, 495 cases of SCC, and 9423 cases of BCC.
Results: Women with melanoma were more likely to have a family history of melanoma (melanoma: RR 1.94, 95% confidence interval [CI] 1.36–2.76; SCC: RR 0.82, 95% CI 0.58–1.37; BCC: RR 1.49, 95% CI 1.38–1.62) and 6 or more moles on the left arm (melanoma: RR 3.66, 95% CI 2.15–6.24; SCC: RR 1.53, 95% CI 0.83–2.79; BCC: RR 1.48, 95% CI 1.28–1.72). Polytomous logistic regression analysis showed that age at diagnosis (P < 0.0001), family history of melanoma (P = 0.016), and number of moles on the left arm (P = 0.007) were significantly different across the 3 cancers.
Conclusions: This prospective observational study demonstrated that known phenotypic factors for skin cancer have a differential impact on the risk of melanoma, SCC, and BCC.

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Background: Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers.
Methods: The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison.
Results: About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9).
Conclusions: This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.

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Background: Good medical care results in long survival for patients with Parkinson’s disease (PD). However, little is known about the burden of PD comorbidity and mortality in Japan. This is the first study to examine comorbid diseases of PD decedents and extrapolate PD death rates from multiple-cause coding mortality data for the total population of Japan.
Methods: Data for 4589 certified deaths due to PD as the underlying cause of death (ICD-10 code: G20) were obtained from the 2008 Japanese vital statistics. Of those, comorbidities listed in the death certificates of 477 randomly selected decedents were analyzed. All diseases or conditions mentioned on death certificates were counted and ranked in descending order of frequency. The death rates (per 100 000 population) from PD were calculated using Japanese National Vital Statistics. The estimated rate of deaths with PD was extrapolated using US death data from a multiple-cause coding system, as no such system is available in Japan, with adjustment for the difference in disease structure between countries.
Results: Average age at death was 80.9 years. The top 5 comorbid diseases ranked as contributory causes of death were cerebrovascular diseases (4.0%), dementia (3.8%), diabetes mellitus (3.6%), malignant neoplasm (2.5%), and heart diseases (2.3%). Overall, the death rates from and with PD were 3.6 and 5.8, respectively.
Conclusions: Analysis restricted to data from the underlying-cause coding system underestimated the national burden of PD comorbidity and mortality. Use of death certificates and multiple-cause mortality data complement the existing system.

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Background: Neonatal anthropometric charts of the distribution of measurements, mainly birth weight, taken at different gestational ages are widely used by obstetricians and pediatricians. However, the relationship between delivery mode and neonatal anthropometric data has not been investigated in Japan or other countries.
Methods: The subjects were selected from the registration database of the Japan Society of Obstetrics and Gynecology (2003–2005). Tenth centile, median, and 90th centile of birth weight by sex, birth order, and delivery mode were observed by gestational age from 22 to 42 weeks among eligible singleton births.
Results: After excluding 248 outliers and 5243 births that did not satisfy the inclusion criteria, 144 980 births were included in the analysis. The distribution of 10th centile curves was skewed toward lower birth weights during the preterm period among both first live births and second and later live births delivered by cesarean section. More than 40% of both male and female live births were delivered by cesarean section at 37 weeks or earlier.
Conclusions: The large proportion of cesarean sections influenced the skewness of the birth weight distribution in the preterm period.

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Background: Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene–environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005.
Methods: We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay.
Results: The study group comprised 2124 men and 2395 women with a mean age of 55.8 ± 8.9 years (range, 35–69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency ≥0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P < 0.001).
Conclusions: This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene–environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.

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