Public Health Center-based Prospective Study Research Articles

Development and Validation of Prediction Models for the 5-year Risk of Type 2 Diabetes in a Japanese Population: Japan Public Health Center-based Prospective (JPHC) Diabetes Study.

This study aimed to develop models to predict the 5-year incidence of type 2 diabetes mellitus (T2DM) in a Japanese population and validate them externally in an independent Japanese population. Data from 10,986 participants (aged 46-75 years) in the development cohort of the Japan Public Health Center-based Prospective Diabetes Study and 11,345 participants (aged 46-75 years) in the validation cohort of the Japan Epidemiology Collaboration on Occupational Health Study were used to develop and validate the risk scores in logistic regression models. We considered non-invasive (sex, body mass index, family history of diabetes mellitus, and diastolic blood pressure) and invasive (glycated hemoglobin [HbA1c] and fasting plasma glucose [FPG]) predictors to predict the 5-year probability of incident diabetes. The area under the receiver operating characteristic curve was 0.643 for the non-invasive risk model, 0.786 for the invasive risk model with HbA1c but not FPG, and 0.845 for the invasive risk model with HbA1c and FPG. The optimism for the performance of all models was small by internal validation. In the internal-external cross-validation, these models tended to show similar discriminative ability across different areas. The discriminative ability of each model was confirmed using external validation datasets. The invasive risk model with only HbA1c was well-calibrated in the validation cohort. Our invasive risk models are expected to discriminate between high- and low-risk individuals with T2DM in a Japanese population.

Dietary Consumption of Antioxidant Vitamins in Relation to Prostate Cancer Risk in Japanese Men: The Japan Public Health Center-based Prospective Study.

Many epidemiological studies have investigated dietary intake of antioxidant vitamins in relation to prostate cancer risk in Western countries, but the results are inconsistent. However, few studies have reported this relationship in Asian countries. We investigated the association between intake of vitamins, including lycopene, α-carotene, β-carotene, vitamin C, vitamin E, with prostate cancer risk in the Japan Public Health Center-based Prospective (JPHC) study. 40,720 men without history of cancer finished the food frequency questionnaire (FFQ) and were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prostate cancer risk were calculated according to the quintiles of energy-adjusted intake of vitamins using Cox models. After an average of 15.2 years (617,599 person-years in total) of follow-up, 1,386 cases of prostate cancer were identified, including 944 localized cases and 340 advanced cases. No associations were observed in consumption of antioxidant vitamins, including α-carotene, β-carotene, vitamin C, and vitamin E, and prostate cancer risk. Although higher lycopene intake was associated with increased risk of prostate cancer (highest vs lowest quintile, HR 1.24; 95% CI, 1.04-1.47; P for trend = 0.01), there was a null association of lycopene intake with risk of prostate cancer detected by subjective symptoms (HR 1.12; 95% CI, 0.79-1.58; P for trend = 0.11). Our study suggested no association between antioxidant intake of vitamins and prostate cancer risk.

Long-term use of anti-cholesterol drugs and cancer risks in a Japanese population

Several studies have investigated the association between the use of anti-cholesterol drugs and cancer risks, of which results have been inconsistent. This study included 67,768 participants from the Japan Public Health Center-based Prospective Study. The data on anti-cholesterol drug use was collected using three questionnaires of the survey conducted every five years. We divided the participants into three groups according to the duration of the anti-cholesterol drug use. Multivariable-adjusted Cox proportional hazard regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). During the 893,009 person-years of follow-up from the 10-year follow-up survey, 8,775 participants (5,387 men and 3,388 women) were newly diagnosed with cancers. The duration of anti-cholesterol drug use was significantly associated with a decreased risk of liver cancer (HR:0.26, 95% CI 0.11–0.64 in > 5 y group) and with an increased risk of pancreatic cancer (HR:1.59, 95% CI 1.03–2.47 in > 5 y group). Moreover, a different trend was observed between men and women in the association with the risk of lung cancer. This study suggested that long-term use of anti-cholesterol drugs may have associations with a decreased incidence of liver cancer and with an increased incidence of pancreatic cancers.

Sleep duration, its change, and risk of dementia among Japanese: The Japan Public Health Center-based Prospective Study

ObjectivePrevious findings on the association between sleep duration, changes in sleep duration, and long-term dementia risk were mixed. Thus, we aimed to investigate the association between midlife sleep duration, its change, and dementia. MethodsWe recruited 41,731 Japanese (40–71 years) and documented their habitual sleep duration at baseline (1990–1994) and a 5-year follow-up survey. Changes in sleep duration were calculated as differences between baseline and 5-year measurements. We identified dementia using the Long-Term Care Insurance system (2007–2016). Hazard ratios (HRs) and 95% confidence intervals (CIs) of dementia were calculated using the area-stratified Cox model. ResultsDuring 360,389 person-years, 4621 participants exhibited dementia. The multivariable HRs of dementia compared with 7 h of sleep were 1.13 (95% CI: 0.98–1.30) for 3–5 h, 0.93 (0.85–1.02) for 6 h, 1.06 (0.99–1.14) for 8 h, 1.13 (1.01–1.27) for 9 h, and 1.40 (1.21–1.63) for 10–12 h with a J-shaped fashion (p for linear < 0.001 and quadratic < 0.001). For its change, the HRs compared with no change were 1.02 (0.90–1.16) for decreased ≥2 h, 0.95 (0.88–1.03) for decreased 1 h, 1.00 (0.91–1.09) for increased 1 h, and 1.37 (1.20–1.58) for increased ≥2 h. The positive association for decreased sleep duration was observed in individuals with an initial sleep duration of ≤7 h, but not in those with ≥8 h (p for interaction = 0.007). ConclusionsLong and increased sleep duration was associated with a higher risk of dementia.

Relation between a history of glaucoma and subjective happiness: the JPHC-Next study

ObjectiveThis population-based, cross-sectional study was performed to investigate the relationship between a history of glaucoma and subjective happiness.Methods and analysisWe conducted a cross-sectional questionnaire-based survey of 92 397 Japanese men...

Maternal dietary intake of fish and child neurodevelopment at 3 years: a nationwide birth cohort-The Japan Environment and Children's Study.

Results on the association between fish intake during pregnancy and a reduction in neurodevelopmental delays in children have been inconsistent, with some reports finding an association and others finding none. Because neurodevelopmental delays are more pronounced at the age of 3 years, their association needs to be examined at this age. After exclusion and multiple imputation from a dataset comprising 104,057 records from the Japan Environment and Children's Study, logistic regression analysis was conducted in quintiles to evaluate the association between maternal fish intake during pregnancy and child neurodevelopment at age 3 years in 91,909 mother-child pairs. The Food Frequency Questionnaire (FFQ), validated in the Japan Public Health Center-Based Prospective Study for the Next Generation, was used to assess maternal fish intake during pregnancy. The Ages and Stages Questionnaires-3 was used to assess children's neurodevelopment in five domains: communication, gross motor, fine motor, problem-solving, and personal-social. Consistently lower odds were found for the highest vs. lowest quintile for the domains of communication, fine motor, problem-solving, and personal-social but not gross motor skills, with adjusted odd ratios (95% confidence intervals) of 0.89 (0.80-0.998), 0.90 (0.83-0.97), 0.86 (0.80-0.94), 0.87 (0.77-0.98), and 1.04 (0.94-1.16), respectively. The trend for lower odds of symptoms of neurodevelopmental delays across quintiles of higher maternal fish intake were significant for fine motor, problem-solving, and personal-social but not communication or gross motor. Fish consumption during pregnancy may be associated with a reduced risk of neurodevelopmental delay in 3-year-olds, particularly in the fine motor, problem-solving, and personal-social domains. Continued investigation after the age of 3 could further clarify the association.

Validity of self-reported Helicobacter pylori eradication treatment from questionnaire and interview surveys of the JPHC-NEXT study: comparison with prescription history from insurance claims data.

We aimed to evaluate the validity of self-administered questionnaire surveys and face-to-face interview surveys for the detection of Helicobacter pylori eradication therapy. Participants were a cohort, aged 40-74 years, living in three different locations of Japan, who took part in the baseline survey (2011-2012) of the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT). Five years after the baseline survey, a questionnaire and interview survey were independently conducted to determine the history of Helicobacter pylori eradication treatment over the 5-year period. Prescription of Helicobacter pylori eradication medications in national insurance claims data from the baseline survey to the 5-year survey was used as a reference standard. In total, 15,760 questionnaire surveys and 8,006 interview surveys were included in the analysis. There were 3,471 respondents to the questionnaire and 2,398 respondents to the interview who reported having received Helicobacter pylori eradication treatment within the past five years. Comparison of the questionnaire survey to national insurance claims data showed a sensitivity of 95.1% (2213/2328), specificity of 90.6% (12174/13432), positive predictive value of 63.8% (2213/3471), negative predictive value of 99.1% (12174/12289), and Cohen's Kappa value of 0.71. Respective values of the interview survey were 94.4% (1694/1795), 88.7% (5507/6211), 70.6% (1694/2398), 98.2% (5507/5608), and 0.74. Both the questionnaire and the interview showed high sensitivity, high specificity, and good agreement with the insurance claim prescriptions data. Some participants may have received eradication treatment without going through the public insurance claim database, resulting in a low positive predictive value.

Validity of the intake of sugars, amino acids, and fatty acids estimated using a self-administered food frequency questionnaire in middle-aged and elderly Japanese: the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT) Protocol Area.

The Japanese database of food composition was revised in 2020, during which both the number of food items and the number of food items measured for sugars, amino acids, and fatty acids were increased. We evaluated the validity of estimated intakes of sugars, amino acids and fatty acids using a long-food frequency questionnaire (FFQ) among middle-aged and elderly Japanese. From 2012 to 2013, 240 men and women aged 40-74 years from five areas in the JPHC-NEXT protocol were asked to respond to the long-FFQ and provide a 12-day weighed food record (WFR) as reference. The long-FFQ, which included 172 food and beverage items and 11 seasonings, was compared with a 3-day WFR, completed during each distinct season, and validity was assessed using Spearman's correlation coefficients. Percentage differences based on the long-FFQ with the 12-day WFR in men and women varied from -83.9% to 419.6%, and from -75.8% to 623.1% for sugars, -17.5% to 2.8% and -5.8% to 19.6% for amino acids, and -58.5% to 78.8% and -43.4% to 129.3% for fatty acids, respectively. Median values of correlation coefficients for the long-FFQ in men and women were 0.52 and 0.42 for sugars, 0.38 and 0.37 for amino acids, and 0.42 and 0.42 for fatty acids, respectively. The long-FFQ provided reasonable validity in estimating the intakes of sugars, amino acids, and fatty acids in middle-aged and elderly Japanese. Although caution is warranted for some nutrients, these results may be used in future epidemiological studies.

The effect of age on the relationship between body mass index and risks of incident stroke subtypes: The JPHC study

ObjectiveThe associations between body mass index (BMI) and stroke subtypes, particularly intracerebral hemorrhage, have not been consistent. Such inconsistencies may be due to differences in the age at which BMI was obtained. We examined the possible age modifications in the association between BMI and stroke risk. Materials and MethodsWe followed 88,754 participants, aged 40–69 years at baseline (1990-1994), of the Japan Public Health Center-based prospective (JPHC) study for stroke incidence. BMI was obtained using self-reported body weight and height, which were categorized using the following cut-off points: 18.5, 21, 23, 25, 27.5, and 30 kg/m2. Time-dependent Cox proportional hazards models that updated BMI and covariates using 5- and 10-year questionnaire responses were used to estimate hazard ratios and 95 % confidence intervals. The analyses were stratified by age group (40–59 and ≥60 years) and the age of the individuals was updated. ResultsDuring the median follow-up period of 19 years, we documented 4,690 strokes, including 2,781 ischemic strokes and 1,358 intracerebral hemorrhages. After adjusting for sex, age, smoking, alcohol consumption, leisure-time physical activity, history of hypertension, dyslipidemia, and diabetes mellitus, we observed a positive linear association between BMI and ischemic stroke (linear trend, p < 0.001) in both age groups (interaction p>0.05). In contrast, a curvilinear association between BMI and intracerebral hemorrhage was observed in both the middle (curvilinear trend, p=0.017) and the older group (curvilinear trend, p=0.098) (interaction p>0.05). ConclusionBMI and stroke associations did not vary significantly with age, although the association may differ according to subtype.

P140: Midlife diet and risk of dementia/mild cognitive impairment

The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake was assessed on two occasions: in the years 1995 and 2000 (aged 45-64 in 1995). In 2014-2015, approximately 1300 participants from Saku district in Nagano prefecture completed a mental health screening including later life depression and cognitive decline (i.e., mild cognitive impairment (MCI) and dementia). We used logistic regression analyses to calculate odds ratios (ORs) for MCI and dementia. Based on this survey, we found the following characteristics of midlife diet, which may be useful information to prevent cognitive decline/dementia.1.High-density lipoprotein cholesterol (HDL-C) and later cognitive decline (Svensson et al. Transl Psychiatry, 2019): Midlife high-density lipoprotein cholesterol (HDL-C) is a measure which could help identify individuals at reduced risk of developing age-related cognitive decline. Compared to the lowest HDL-C quartile, the highest HDL-C quartile was significantly inversely associated with MCI. High HDL-C (quartiles 2-4) was inversely associated with dementia compared to low HDL-C (quartile 1).2.Dietary fish and n-3 polyunsaturated fatty acid (PUFA) and later cognitive decline (Nozaki et al. J Alzheimers Dis, 2021): Higher intake of fish, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in midlife significantly reduced risks of dementia.3.Intake of soy and the isoflavone and later cognitive decline (Svensson et al. J Alzheimers Dis, 2021): Compared to the lowest dietary quartile of energy-adjusted isoflavone genistein intake, the highest quartile was significantly associated with late-life cognitive impairment.4.Cancer/diabetes and later cognitive decline (Sadahiro et al. Psychiatry Clin Neurosci, 2019): Comorbid cancer and diabetes from midlife may increase the risk of MCI or dementia in later life. In addition to the increased dementia risk associated with diabetes on the basis of insulin resistance, cancer and cancer therapies may also interfere with cognitive function via insulin resistance.

Body mass index trajectories and mortality risk in Japan using a population-based prospective cohort study: the Japan Public Health Center-based Prospective Study.

Recent studies have found that long-term changes in weight during adulthood are associated with a high risk of mortality. The objective of this study was to characterize body mass index (BMI) trajectories during adulthood and to examine the association between BMI trajectories and risk of death in the Japanese population. The data were extracted from Japan Public Health Center-based Prospective Study-a population-based prospective cohort study in Japan with participants aged 40-69 years followed over 20 years. The participants were categorized into multiple BMI trajectory groups using the latent class growth model. The Cox proportional-hazards model was conducted using all-cause mortality and cause-specific mortality as outcomes and the identified BMI trajectory groups as a predictor. In total, 65 520 participants were included in the analysis. Six BMI trajectory groups were identified: underweight stable (Group 1), low-to-high normal (Group 2), high-to-low normal (Group 3), normal to overweight (Group 4), overweight to normal (Group 5) and normal to obese (Group 6). Our Cox models showed a higher hazard (risk) of all-cause mortality among participants in the BMI-declining groups [Group 3, adjusted hazard ratio (aHR): 1.10, 95% CI: 1.05-1.16; Group 5, aHR: 1.16, 95% CI: 1.08-1.26], underweight stable group (Group 1, aHR: 1.27, 95% CI: 1.21-1.33) and normal to obese group (Group 6, aHR: 1.22, 95% CI: 1.13-1.33) than Group 2 (low-to-high normal BMI trajectory). Stable underweight and weight loss were associated with a high risk of mortality, both of which were uniquely observed in a Japanese population.

Body mass index, weight change in midlife, and dementia incidence: the Japan Public Health Center-based Prospective Study.

Insufficient evidence exists on the sex-specific associations of body mass index (BMI) and weight change through midlife with dementia incidence, especially in Asian populations. For 37,414 Japanese residents aged 40 to 59 years, BMIs at baseline (year 1990 or 1993) and 10-year follow-ups were obtained. Weight changes between baseline and 10-year follow-ups were determined. Disabling dementia incidence from 2006 to 2016 was ascertained using long-term care insurance (LTCI) certifications. Hazard ratios (HRs) were computed. Increased dementia risk was observed with obesity at baseline and with underweight at 10-year follow-ups. Weight loss after baseline was at greater risk than weight gain. No sex difference was observed. In both sexes, obesity in midlife increased the risk of developing dementia with increasing impacts of weight loss after midlife. A healthy body weight throughout adulthood is beneficial for dementia prevention. Obesity in midlife is a risk factor for incident dementia.Weight loss is a bigger risk factor than weight gain in later midlife.Association of BMI and weight change in midlife with dementia does not vary by sex.

Impact of Cardiovascular Disease on the Death Certificate Diagnosis of Heart Failure, Ischemic Heart Disease, and Cerebrovascular Disease　- The Japan Public Health Center-Based Prospective Study.

There is considerable interest in the trending discrepancy between ischemic heart disease (IHD) and heart failure (HF) in vital statistics. Clinically, acute myocardial infarction (AMI) and stroke are closely associated with HF, but their contribution to HF as the underlying cause of death (UCD) is unclear.Methods and Results: In 1990 and 1992-1993, we enrolled a total of 140,420 residents of Japanese nationality (aged 40-69 years) from 11 public health center areas. We prospectively examined the occurrence of cardiovascular disease (CVD), including AMI, sudden cardiac death within 1 h (SCD), and stroke, and analyzed the 14,375 participants without a history of CVD at baseline who died during the 20-year follow-up. A time-dependent Cox proportional hazards model was used to estimate hazard ratios and the population attributable fraction (PAF) of AMI, AMI+SCD, stroke, and CVD for deaths due to HF, IHD, and cerebrovascular disease as the UCD, adjusted for individuals' lifestyles and comorbid conditions. The PAF of AMI for HF deaths was 2.4% (95% confidence interval [CI] 1.7-2.9%), which increased to 12.0% (95% CI 11.6-12.2%) for AMI+SCD. The PAF of CVD-attributed HF deaths was estimated to be 17.6% (95% CI 15.9-18.9%). HF as the UCD was partly explained by CVD. The data imply that most HF deaths reported in vital statistics may be associated with underlying causes other than CVD.

Reproductive factors in the risk of bladder cancer and upper urinary tract cancer: The Japan Public Health Center-based Prospective Study.

Reproductive factors are hypothesized to play a role in the incidence of bladder cancer (BC) and upper urinary tract cancer (together, urothelial cancer (UC)). However, evidence regarding these associations is limited, particularly in Asian populations. We analyzed data from 55,882 females aged 40-69 years, and performed Cox proportional hazards regression analyses with three types of adjustment, namely age; reproductive factor of interest and covariates in addition to age (conventional model); and other reproductive factors in addition to the multivariable adjusted model (reproductive model). During an average of 20.2 years of follow-up, 194 UC cases (145 BC cases and 49 UUTC cases) were identified. Early age at natural menopause (<44 years, compared to 49-51 years) increased BC risk in the reproductive model (HR=2.09 (95% CI=1.04-4.20)). An association between UC/BC and age at menopause, including both natural and surgical/induced, was significant in the reproductive model [HR=1.74 (95% CI=1.09-2.77), and HR=1.94 (95% CI=1.15-3.28), respectively]. Early age at natural menopause was suggested to increase UC risk in the reproductive model (HR=1.78 (95% CI=0.93-3.42)). Our findings suggest a significant association between age at menopause and incidence of UC/BC among Asian populations. This study aids understanding the role of reproductive factors in UC/BC incidence. In Japanese populations, age at menopause is suggested to be associated with UC/BC incidence, especially regarding early natural menopause.

Dietary Fish and n-3 Polyunsaturated Fatty Acid Consumption, and Renal Cell Carcinoma Risk in Japan: The Japan Public Health Center-Based Prospective Study.

Previous epidemiologic studies found inconsistent associations between fish consumption and renal cell carcinoma (RCC). Although the consumption of n-3 polyunsaturated fatty acids (PUFA) was reported to protect against the development of some types of cancer, little is known regarding its association with RCC. We investigated the association between fish and n-3 PUFA consumption and RCC risk using the Japan Public Health Center-based Prospective Study. We examined data from 84,063 eligible Japanese participants aged 45 to 74 years who responded to a validated food frequency questionnaire for Cohort I in 1995 and Cohort II in 1998. The participants were followed-up until 2013. HRs and 95% confidence intervals (CI) were estimated using a multivariable-adjusted Cox proportional hazard model, and the exposure level was categorized into quartiles. Among the 1,272,298 person-years of follow-up, 262 cases of newly diagnosed RCC were identified. The multivariate-adjusted HRs for the highest vs. lowest quartile of fish, including shellfish, were (HR = 1.43; 95% CI, 0.98-2.07) and the individual marine n-3 PUFAs were (HR = 1.56; 95% CI, 1.07-2.28; Ptrend = 0.09) for eicosapentenoic acid, (HR = 1.81; 95% CI, 1.27-2.59; Ptrend = 0.01) for docosapentaenoic acid, and (HR = 1.56; 95% CI, 1.07-2.27; Ptrend = 0.09) for docosahexaenoic acid. RCC were further categorized on the basis of diagnosis methods and cancer stage, and the positive correlation did not change substantially. We demonstrated that high consumption of n-3 PUFA is associated with RCC risk. The positive association between n-3 PUFA and RCC risk was observed in Japanese who consume higher amounts of fish than Western populations.

Midlife intake of the isoflavone genistein and soy, and the risk of late-life cognitive impairment: the JPHC Saku Mental Health Study.

The number of people with cognitive impairment, including dementia, in the world is steadily increasing. Although the consumption of isoflavones and soy is associated with a reduced risk of cardiovascular disease, it might also be associated with cognitive impairment. The low number of studies investigating the association between soy/isoflavone intake and cognitive function warrant additional research. The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake of soy and the isoflavone genistein was assessed on two occasions: in the years 1995 and 2000. In 2014-2015, 1299 participants from Nagano prefecture completed a mental health screening. Of these, a total of 1036 participants were included in analyses. Logistic regression was used to determine Odds Ratios (OR) and 95% Confidence Intervals (CI) for the association between midlife energy-adjusted genistein and soy food intake and cognitive impairment. There were 392 cases of cognitive impairment (346 cases of MCI and 46 cases of dementia). Compared to the lowest dietary quartile of energy-adjusted genistein intake, the highest quartile was significantly associated with cognitive impairment (OR=1.51; 95% CI, 1.02-2.24; p for trend=0.03) in the final multivariable analysis. High midlife intake of the isoflavone genistein is associated with late-life cognitive impairment.

Bowel movement frequency, stool consistency, and risk of disabling dementia: a population-based cohort study in Japan

ObjectivesThis population-based study aimed to evaluate the association between bowel habits from midlife and dementia. Study designThis was a cohort study using certification records for national long-term care insurance in Japan. MethodsParticipants aged 50 to 79 years who reported bowel habits from eight districts within the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from 2006 to 2016 for incident dementia. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for men and women separately using Cox proportional hazards models accounting for various lifestyle factors and medical histories. ResultsAmong 19,396 men and 22,859 women, 1889 men and 2685 women were diagnosed with dementia. In men, the multivariable-adjusted HRs compared with bowel movement frequency (BMF) of once/day were 1.00 (95% CI: 0.87–1.14) for twice/day or more, 1.38 (1.16–1.65) for 5–6 times/week, 1.46 (1.18–1.80) for 3–4 times/week, and 1.79 (1.34–2.39) for <3 times/week (P for trend <0.001). In women, the corresponding HRs were 1.14 (0.998–1.31), 1.03 (0.91–1.17), 1.16 (1.01–1.33), and 1.29 (1.08–1.55) (P for trend = 0.043). Harder stool was associated with higher risk (P for trend: 0.0030 for men and 0.024 for women), with adjusted HRs compared to normal stool of 1.30 (1.08–1.57) for hard stool and 2.18 (1.23–3.85) for very hard stool in men, and 1.15 (1.002–1.32) and 1.84 (1.29–2.63) in women. ConclusionsLower BMF and harder stool were each associated with higher risk of dementia.

Lack of significant associations between single nucleotide polymorphisms in LPAL2-LPA genetic region and all cancer incidence and mortality in Japanese population: The Japan public health center-based prospective study

BackgroundHigh lipoprotein (a) level is an established cardiovascular risk, but its association with non-cardiovascular diseases, especially cancer, is controversial. Serum lipoprotein (a) levels vary widely by genetic backgrounds and are largely determined by the genetic variations of apolipoprotein (a) gene, LPA. In this study, we investigate the association between SNPs in LPA region and cancer incidence and mortality in Japanese. MethodsA genetic cohort study was conducted utilizing the data from 9923 participants in the Japan Public Health Center-based Prospective Study (JPHC Study). Twenty-five SNPs in the LPAL2-LPA region were selected from the genome-wide genotyped data. Cox regression analysis adjusted for the covariates and competing risks of death from other causes, were used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of overall and site-specific cancer incidence and mortality, for each SNP. ResultsNo significant association was found between SNPs in the LPAL2-LPA region and cancer incidence or mortality (overall/site-specific cancer). In men, however, HRs for stomach cancer incidence of 18SNPs were estimated higher than 1.5 (e.g., 2.15 for rs13202636, model free, 95%CI: 1.28–3.62) and those for stomach cancer mortality of 2SNPs (rs9365171, rs1367211) were estimated 2.13 (recessive, 95%CI:1.04–4.37) and 1.61 (additive, 95%CI: 1.00–2.59). Additionally, the minor allele for SNP rs3798220 showed increased death risk from colorectal cancer (CRC) in men (HR: 3.29, 95% CI:1.59 – 6.81) and decreased CRC incidence risk in women (HR: 0.46, 95%CI: 0.22–0.94). Minor allele carrier of any of 4SNPs could have risk of prostate cancer incidence (e.g., rs9365171 dominant, HR: 1.71, 95%CI: 1.06–2.77). ConclusionsNone of the 25 SNPs in the LPAL2-LPA region was found to be significantly associated with cancer incidence or mortality. Considering the possible association between SNPs in LPAL2-LPA region and colorectal, prostate and stomach cancer incidence or mortality, further analysis using different cohorts is warranted.

Validation Study of Diabetes Definitions Using Japanese Diagnosis Procedure Combination Data Among Hospitalized Patients.

Validation studies of diabetes definitions using nationwide healthcare databases are scarce. We evaluated the validity of diabetes definitions using disease codes and antidiabetic drug prescriptions in the Japanese Diagnosis Procedure Combination (DPC) data via medical chart review. We randomly selected 500 records among 15,334 patients who participated in the Japan Public Health Center-Based Prospective Study for the Next Generation in Yokote City and who had visited a general hospital in Akita between October 2011 and August 2018. Of the 500 patients, 98 were linked to DPC data; however, only 72 had sufficient information in the medical chart. Gold standard confirmation was performed by board-certified diabetologists. DPC-based diabetes definitions were based on the International Classification of Diseases, 10th Revision codes and antidiabetic prescriptions. Sensitivity, specificity, and the positive and negative predictive values (PPV and NPV, respectively) of DPC-based diabetes definitions were evaluated. Of 72 patients, 23 were diagnosed with diabetes using chart review; 19 had a diabetes code, and 13 had both a diabetes code and antidiabetic prescriptions. The sensitivity, specificity, PPV, and NPV were 89.5% (95% confidence interval [CI], 66.9-98.7%), 96.2% (95% CI, 87.0-99.5%), 89.5% (95% CI, 66.9-98.7%), and 96.2% (95% CI, 87.0-99.5%), respectively, for (i) diabetes codes alone; 89.5% (95% CI, 66.9-98.7%), 94.3% (95% CI, 84.3-98.8%), 85.0% (95% CI, 62.1-96.8%), and 96.2% (95% CI, 86.8-99.5%) for (ii) diabetes codes and/or prescriptions; 68.4% (95% CI, 43.4-87.4%), 100% (95% CI, 93.3-100%), 100% (95% CI, 75.3-100%), and 89.8% (95% CI, 79.2-96.2%) for (iii) both diabetes codes and prescriptions. Our results suggest that DPC data can accurately identify diabetes among inpatients using (i) diabetes codes alone or (ii) diabetes codes and/or prescriptions.

Associations between dairy intake and mortality due to all-cause and cardiovascular disease: the Japan Public Health Center-based prospective study

BackgroundSome studies have investigated the relation between dairy products and mortality, but with inconsistent results.ObjectiveWe examined the association between the consumption of dairy products and the risk of all-cause, cancer-related, and cardiovascular disease (CVD)-related mortality.MethodsFrom the Japan Public Health Center-based Prospective (JPHC) study, 43,117 males and 50,193 females with no history of cancer or CVD finished the food frequency questionnaire (FFQ) and were included in the study. Intake of dairy products was assessed using the FFQ and adjusted for total energy by using the residual method. We used multivariate Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for mortality risk in males and females.Results14,211 deaths in males and 9547 deaths in females from all causes were identified during an average follow-up of 19.3 years. For males, total dairy consumption was nonlinearly and significantly associated with lower risk of mortality from all causes [the third quartile, HR = 0.87 (0.83, 0.91), the fourth quartile, HR = 0.89 (0.85, 0.94), P for nonlinearity < 0.001] and CVD [the third quartile, HR = 0.77 (0.70, 0.85), the fourth quartile, HR = 0.78 (0.70, 0.86), P for nonlinearity < 0.001]. Milk and fermented milk intake were inversely associated with all-cause and CVD-related mortality in males. Cheese consumption was inversely associated with CVD-related mortality among males. There was no association between total dairy intake and mortality risk among females.ConclusionFor Japanese people, consumption of dairy products was associated with a decreased risk of mortality from all-cause and cardiovascular diseases among males.