The impact of treatment on the psychological burden of mothers of children with chronic hepatitis C virus infection: a multicenter, questionnaire survey.

Mothers of children with chronic hepatitis C virus (HCV) infection experience anxiety about the health of their children. In this study we assessed an impact of treating children with chronic HCV infection on the psychological burden of their mothers. This was a multicenter, questionnaire survey conducted at six institutions in Japan. A newly-developed questionnaire for this study was used to assess changes in the mothers' various concerns regarding HCV infection and thoughts about their child's HCV infection. Responses at the time of diagnosis and at the time of the survey were compared between mothers of children who had received treatment and those without treatment. Responses were received from 36 of 37 eligible mothers (11 and 25, non-treatment and treatment groups, respectively). All children in treatment group had successfully eliminated the virus. Mothers in both groups were psychologically stressed in various ways, including concern about their child's health in the present and future at the time of diagnosis, concern about school, employment, and marriage, concern about the behavior of others towards them and infecting others with HCV, and feelings of guilt regarding their child. These concerns were significantly lower in the present compared to at the time of diagnosis in treatment group, and the rate of decrease was significantly higher in treatment group compared to non-treatment group. Successful treatment greatly reduced mothers' concerns about their children's HCV infection, indicating that treatment during childhood is beneficial from the perspective of the mothers' psychological burden.

Comparative accuracy of cervical cancer screening strategies in healthy asymptomatic women: a systematic review and network meta-analysis.

To compare all available accuracy data on screening strategies for identifying cervical intraepithelial neoplasia grade ≥ 2 in healthy asymptomatic women, we performed a systematic review and network meta-analysis. MEDLINE and EMBASE were searched up to October 2020 for paired-design studies of cytology and testing for high-risk genotypes of human papillomavirus (hrHPV). The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, random-effects network meta-analysis of test accuracy, and GRADE rating. Twenty-seven prospective studies (185,269 subjects) were included. The combination of cytology (atypical squamous cells of undetermined significance or higher grades) and hrHPV testing (excepting genotyping for HPV 16 or 18 [HPV16/18]) with the either-positive criterion (OR rule) was the most sensitive/least specific, whereas the same combination with the both-positive criterion (AND rule) was the most specific/least sensitive. Compared with standalone cytology, non-HPV16/18 hrHPV assays were more sensitive/less specific. Two algorithms proposed for primary cytological testing or primary hrHPV testing were ranked in the middle as more sensitive/less specific than standalone cytology and the AND rule combinations but more specific/less sensitive than standalone hrHPV testing and the OR rule combination. Further research is needed to assess these results in population-relevant outcomes at the program level.

Does Direct-to-Consumer Personal Genetic Testing Improve Gynecological Cancer Screening Uptake among Never-Screened Attendees? A Randomized Controlled Study.

The clinical impact of direct-to-consumer genetic testing (DTC-GT) on health behavior change has remained controversial. The aim of this study is to clarify the short-term effects of DTC-GT on gynecological cancer screening uptake among middle-aged never-screened Japanese women in a randomized controlled trial (RCT). A total of 144 women aged 45-50 who had never undergone gynecological cancer screening were randomly selected to receive health education (control group), or health education and DTC-GT (intervention group), at a 1:1 ratio. We compared the gynecological screening uptake during the follow-up period. Furthermore, to estimate the impact of learning of an elevated genetic cancer risk in the intervention group, we conducted an analysis dichotomized by genetic risk category. A total of 139 women completed the one-year follow-up survey (69 in the control group and 70 in the intervention group). The follow-up period did not differ between control and intervention groups (the median follow-up period was 276 days and 279 days, respectively, p = 0.746). There were 7 (9.7%) women in the control group and 10 (13.9%) in the intervention group who attended breast cancer screening (p = 0.606), and 9 (12.5%) women from both groups attended cervical cancer screening (p = 1.000). Likewise, there were no significant differences in cancer screening uptake in the analysis stratified by risk category within the intervention group. In conclusion, there was no significant effect of DTC-GT on gynecological cancer screening uptake in this RCT setting. Increasing cancer screening attendance may require a combination of well-established intervention strategies and DTC-GT. Clinical Trial Registration: UMIN-CTR Identifier, UMIN000031709.

National Data Analysis and Systematic Review for Human Resources for Cervical Cancer Screening in Japan.

BACKGROUND: Although cervical cancer screening has been performed as a national program since 1983 in Japan, the participation rate has remained below 20%. Equity of access is a basic requirement for cancer screening. However, taking smears from the cervix has been limited to gynecologists or obstetricians in Japan and it might be a barrier for accessibility. We examined the current access and its available human resources for cervical cancer screening in Japan. METHODS: We analyzed the number of gynecologists and obstetricians among 47 prefectures based on a national survey. A systematic review was performed to clarify disparity and use of human resources in cervical cancer screening, diagnosis, and treatment for cervical cancers in Japan. Candidate literature was searched using Ovid-MEDLINE and Ichushi-Web until the end of January 2020. Then, a systematic review regarding accessibility to cervical cancer screening was performed. The results of the selected articles were summarized in the tables. RESULTS: Although the total number of all physicians in Japan increased from 1996 to 2016, the proportion of gynecologists and obstetricians has remained at approximately 5% over the last 2 decades. 43.6% of municipalities have no gynecologists and obstetricians in 2016. Through a systematic review, 4 English articles and 1 Japanese article were selected. From these 5 articles, the association between human resources and participation rates in cervical cancer screening was examined in 2 articles. CONCLUSIONS: The human resources for taking smears for cervical cancer screening has remained insufficient with a huge disparity among municipalities in Japan. To improve accessibility for cervical cancer screening another option which may be considered could be involving general physicians as potential smear takers.

Net Survival of Elderly Patients with Gynecological Cancer Aged Over 75 Years in 2006-2008

Background: The number of elderly patients with gynecological cancer in Japan is increasing in line with the aging of society. However, little has been reported on the survival of elderly patients aged 75 or older with gynecological cancer in Japan. Methods: To clarify survival in women aged 75 years or older with gynecological cancer, we analyzed data of 4,089 gynecological cancer cases (cervical cancer, 1,309 cases; endometrial cancer, 1,319 cases; and ovarian cancer, 1,461 cases) in patients aged 75 or older from 21 population-based cancer registries in Japan, diagnosed in 2006-2008. We calculated the net survival (NS) of younger (75-79 years old), older (80-84 years old) and the oldest age group (85-99 years old). We also calculated NS stratified by extent of disease and histological type. Results: Five-year NS of cervical cancer patients was 54.5% in the younger age group, 40.8% in the older age group and 28.2% in the oldest age group. Five-year NS of endometrial cancer patients was 64.5%, 51.6% and 39.0% in the younger, older and oldest age groups, respectively. Five-year NS of ovarian cancer was 34.7%, 18.8% and 8.3%, respectively. Conclusion: We estimated NS in elderly patients aged 75 years or older with gynecological cancers in Japan using data from population-based cancer registries.

Frequency of unsatisfactory cervical cytology smears in cancer screening of Japanese women: A systematic review and meta-analysis.

The Bethesda system (TBS) has been used for cervical cytological diagnosis in Japan since 2008. Evaluation of specimen adequacy is the most important aspect of quality assurance and for precise diagnosis in TBS. A systematic review and meta-analysis were carried out to assess the unsatisfactory specimen rate in the primary cervical cancer screening setting in Japan. Ovid Medline and Ichushi-Web databases were searched from inception through to May 2017. Prospective and retrospective studies that reported the proportion of unsatisfactory specimens in healthy asymptomatic Japanese women in a cervical cancer screening program were eligible for inclusion; 17 studies were included in the meta-analysis. The random-effects model meta-analysis calculated summary estimates of the unsatisfactory rate of 0.60% (95% confidence interval [CI], 0.18-1.96%; I2 = 99%) for conventional cytology and 0.04% (95% CI, 0.00-0.35%; I2 = 99%) for liquid-based cytology (LBC). However, comparative results between conventional and liquid-based cytology, based on four direct and nine comparative studies, showed no significant difference (summary odds ratio = 3.5 × 10-2 favoring LBC [95% CI, 6.9 × 10-4 -1.7]; I2 = 98%). In the subgroup analyses and meta-regressions, use of non-cotton devices for conventional cytology and use of a particular platform for LBC were associated with lower unsatisfactory rates. Meta-regression also suggested chronological improvement in unsatisfactory rates for both tests. In Japanese cervical cancer screening programs, conventional cytology remains prevalent. Future research needs to focus on evaluating the impact of screening programs using LBC by comparing the accuracy, performance, and cost-effectiveness with conventional cytology in the Japanese population.

A genome-wide association study in the Japanese population identifies the 12q24 locus for habitual coffee consumption: The J-MICC Study.

Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12-13 and 5q33.3) that met suggestive significance (P < 1 × 10-6). In the replication stage (n = 4,949), the lead variant for the 12q24.12-13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10-6), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10-16 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.

Improvement in 5-Year Relative Survival in Cancer of the Corpus Uteri From 1993-2000 to 2001-2006 in Japan.

BACKGROUND: Medical circumstances in Japanese patients with cancer of the corpus uteri have greatly changed since the late 1990s, including the introduction of concomitant therapy with taxane and platinum. We evaluated changes in survival rates for this cancer following these advances by analyzing data from population-based cancer registries in Japan. METHODS: Data were available for 8562 cases of cancer of the corpus uteri from six prefectural cancer registries. We defined the two periods of 1993-2000 (1st period) and 2001-2006 (2nd period). Relative survival (RS) in each period was calculated to assess changes using an excess mortality model, with adjustment for age group (15-54, 55-69, and 70-99 years), extent of disease (localized, regional, and distant), and histological subtype. RESULTS: Overall 5-year RS improved from 77.7% in the 1st period to 80.2% in the 2nd period, with an excess hazard ratio (EHR) of 0.785 (95% confidence interval [CI], 0.705-0.873). Five-year RS significantly improved in the group aged 55-69 years, in all groups by extent of disease, and in the endometrioid adenocarcinoma group. In particular, 5-year RS significantly improved in patients with endometrioid adenocarcinoma, from 84.5% to 89.7%, with an EHR of 0.698 (95% CI, 0.560-0.870). CONCLUSION: Overall 5-year RS for cancer of the corpus uteri in Japan improved from the 1990s to early 2000s. These improvements might have been aided by the comprehensive medical development of management for this cancer, including the spread of concomitant therapy with taxane and platinum as a standard adjuvant chemotherapy in the early 2000s.

Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women.

Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47-69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2-Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.

Coffee consumption and the risk of colorectal cancer by anatomical subsite in Japan: Results from the HERPACC studies.

Consumption of coffee, a popular beverage worldwide, has been associated with lower colorectal cancer (CRC) risk. Although CRC exhibits different biological characteristics by anatomical subsite, the possibly heterogeneous impact of coffee on CRC by anatomical subsite has remained unclear. Here, we conducted two case-control studies to examine the association between coffee consumption and CRC risk as well as risk by anatomic subsite among Japanese using data from the Hospital-based Epidemiological Research Program at Aichi Cancer Center I and II (HERPACC-I and II). Subjects were enrolled in HERPACC-I between 1988 and 2000 and in HERPACC-II between 2001 and 2005. Coffee consumption was measured with a self-administered questionnaire. A conditional logistic regression model was used to calculate odds ratios (ORs) of CRC with coffee consumption, adjusted for potential confounders of age, smoking, alcohol drinking, red meat intake, BMI, exercise, family history of CRC, and diabetes mellitus history. We estimated summary ORs by pooling study-specific ORs with a fixed effects model. In total, 2,696 CRC cases and 13,480 non-cancer outpatients as controls were included. Overall, compared to non-drinkers, ORs of less than 1 cup/day, 1-2 cups/day and 3 or more cups/day for CRC were 0.88 (95% CI: 0.77-1.00), 0.90 (95% CI: 0.80-1.01) and 0.78 (95% CI: 0.65-0.92), respectively (trend-p = 0.009). Subsite-specific analysis revealed a significant inverse linear trend between coffee consumption and distal colon cancer (p-trend = 0.048), and a tendency toward a lower risk of rectal cancer (p-trend = 0.068). These findings suggest that coffee consumption might impact the prevention of CRC, especially distal colon cancer.

Comparison of weighed food record procedures for the reference methods in two validation studies of food frequency questionnaires.

BACKGROUND: Although open-ended dietary assessment methods, such as weighed food records (WFRs), are generally considered to be comparable, differences between procedures may influence outcome when WFRs are conducted independently. In this paper, we assess the procedures of WFRs in two studies to describe their dietary assessment procedures and compare the subsequent outcomes. METHODS: WFRs of 12 days (3 days for four seasons) were conducted as reference methods for intake data, in accordance with the study protocol, among a subsample of participants of two large cohort studies. We compared the WFR procedures descriptively. We also compared some dietary intake variables, such as the frequency of foods and dishes and contributing foods, to determine whether there were differences in the portion size distribution and intra- and inter-individual variation in nutrient intakes caused by the difference in procedures. RESULTS: General procedures of the dietary records were conducted in accordance with the National Health and Nutrition Survey and were the same for both studies. Differences were seen in 1) selection of multiple days (non-consecutive days versus consecutive days); and 2) survey sheet recording method (individual versus family participation). However, the foods contributing to intake of energy and selected nutrients, the portion size distribution, and intra- and inter-individual variation in nutrient intakes were similar between the two studies. CONCLUSION: Our comparison of WFR procedures in two independent studies revealed several differences. Notwithstanding these procedural differences, however, the subsequent outcomes were similar.

Natural history of chronic hepatitis B virus infection in children in Japan: a comparison of mother-to-child transmission with horizontal transmission.

BACKGROUND: It is necessary to evaluate the natural history of children with hepatitis B virus (HBV) infection in each country to consider their long-term management. METHODS: A multi-center observational study of children with chronic HBV infection who were diagnosed at age ≤15 years was carried out in 18 hospitals in Japan. RESULTS: We reviewed children with HBV infection including 381 with mother-to-child transmission (MTCT) and 154 with horizontal transmission, genotype C being the most prevalent virus genotype (83%). Children with horizontal transmission were more frequently infected with HBV genotype A or B and more likely to receive interferon therapy than those infected by MTCT. The HBeAg seroconversion rate at 15 years of age was 42% in the MTCT group and 38% in the horizontal group. It was lower in children with genotype C infection than in those infected with other genotypes (33 versus 45%). Hepatitis developed at any age but before 4 years of age the incidence was high in the horizontal group. At 3 years after the onset of the hepatitis, 26% of children with MTCT and 30% of those with horizontal transmission became inactive carriers. The incidences of hepatocellular carcinoma (HCC) at 30 years of age were 6% in the MTCT group and 11% in the horizontal group. CONCLUSIONS: Patients with childhood-onset HBV infection with MTCT and horizontal transmission developed hepatitis and seroconverted to anti-HBe at any age and had a lifetime risk of developing HCC.

Predictors of pretreatment CA125 at ovarian cancer diagnosis: a pooled analysis in the Ovarian Cancer Association Consortium.

PURPOSE: Cancer antigen 125 (CA125) is a glycoprotein expressed by epithelial cells of several normal tissue types and overexpressed by several epithelial cancers. Serum CA125 levels are mostly used as an aid in the diagnosis of ovarian cancer patients, to monitor response to treatment and detect cancer recurrence. Besides tumor characteristics, CA125 levels are also influenced by several epidemiologic factors, such as age, parity, and oral contraceptive use. Identifying factors that influence CA125 levels in ovarian cancer patients could aid in the interpretation of CA125 values for individuals. METHODS: We evaluated predictors of pretreatment CA125 in 13 studies participating in the Ovarian Cancer Association Consortium. This analysis included a total of 5,091 women with invasive epithelial ovarian cancer with pretreatment CA125 measurements. We used probit scores to account for variability in CA125 between studies and linear regression to estimate the association between epidemiologic factors and tumor characteristics and pretreatment CA125 levels. RESULTS: In age-adjusted models, older age, history of pregnancy, history of tubal ligation, family history of breast cancer, and family history of ovarian cancer were associated with higher CA125 levels while endometriosis was associated with lower CA125 levels. After adjusting for tumor-related characteristics (stage, histology, grade), body mass index (BMI) higher than 30 kg/m2 was associated with 10% (95% CI 2, 19%) higher CA125 levels, while race (non-white vs. white) was associated with 15% (95% CI 4, 27%) higher CA125 levels. CONCLUSION: Our results suggest that high BMI and race may influence CA125 levels independent of tumor characteristics. Validation is needed in studies that use a single assay for CA125 measurement and have a diverse study population.

Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies.

Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case-control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study-specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow-up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08-1.28) and former smokers (pHR = 1.10, 95% CI: 1.02-1.18) had worse survival compared with never smoking women. In histotype-stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01-3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00-1.23; former smoking: pHR = 1.12, 95% CI: 1.04-1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis.

Development of a prediction model and estimation of cumulative risk for upper aerodigestive tract cancer on the basis of the aldehyde dehydrogenase 2 genotype and alcohol consumption in a Japanese population.

Alcohol consumption and the aldehyde dehydrogenase 2 (ALDH2) polymorphism are associated with the risk of upper aerodigestive tract cancer, and a significant gene-environment interaction between the two has been confirmed in a Japanese population. To aid the development of a personalized prevention strategy, we developed a risk-prediction model and estimated absolute risks stratified by a combination of the ALDH2 genotype and alcohol consumption. We carried out two age-matched and sex-matched case-control studies: one (630 cases and 1260 controls) for model derivation and the second (654 cases and 654 controls) for external validation. On the basis of data from the derivation study, a prediction model was developed by fitting a conditional logistic regression model using the following predictors: age, sex, smoking, drinking, and the ALDH2 genotype. The risk model, including a combination of the ALDH2 genotype and alcohol consumption, provided high discriminatory accuracy and good calibration in both the derivation and the validation studies: C statistics were 0.82 (95% confidence interval 0.80-0.84) and 0.83 (95% confidence interval 0.81-0.85), respectively, and the calibration plots of both studies remained close to the ideal calibration line. Cumulative risks were obtained by combining odds ratios estimated from the risk model with the age-specific incidence rate and population size. For heavy drinkers with a heterozygous genotype, the cumulative risk at age 80 was above 20%. In contrast, risk in the other groups was less than 5%. In conclusion, modification of alcohol consumption according to the ALDH2 genotype will have a major impact on upper aerodigestive tract cancer prevention. These findings represent a simple and practical model for personalized cancer prevention.

Heterogeneous impact of alcohol consumption according to treatment method on survival in head and neck cancer: A prospective study.

Alcohol consumption is an established risk factor, and also a potential prognostic factor, for squamous cell carcinoma of the head and neck (HNSCC). However, little is known about whether the prognostic impact of alcohol consumption differs by treatment method. We evaluated the association between alcohol drinking and survival by treatment method to the primary site in 427 patients with HNSCC treated between 2005 and 2013 at Aichi Cancer Center Central Hospital (Nagoya, Japan). The impact of alcohol on prognosis was measured by multivariable Cox regression analysis adjusted for established prognostic factors. Among all HNSCC patients, the overall survival rate was significantly poorer with increased levels of alcohol consumption in multivariable analysis (trend P = 0.038). Stratification by treatment method and primary site revealed that the impact of drinking was heterogeneous. Among laryngopharyngeal cancer (laryngeal, oropharyngeal, and hypopharyngeal cancer) patients receiving radiotherapy (n = 141), a significant dose-response relationship was observed (trend P = 0.034). In contrast, among laryngopharyngeal cancer patients treated with surgery (n = 80), no obvious impact of alcohol was observed. This heterogeneity in the impact of alcohol between surgery and radiotherapy was significant (for interaction, P = 0.048). Furthermore, among patients with oral cavity cancer treated by surgery, a significant impact of drinking on survival was seen with tongue cancer, but not with non-tongue oral cancer. We observed a significant inverse association between alcohol drinking and prognosis among HNSCC patients, and its impact was heterogeneous by treatment method and primary site.

Changes in trends in colorectal cancer incidence rate by anatomic site between 1978 and 2004 in Japan.

Although colorectal cancer (CRC), a major type of cancer worldwide, has shown a proximal or right-sided shift in subsite distribution in western countries, trends in subsite incidence in Asian countries remain unclear. Here, we evaluated subsite-specific trends in CRC incidence rate between 1978 and 2004 in Japan using large data from 10 population-based cancer registries. The colorectal sites (C18-C20) were categorized into three groups: proximal colon (C18.0-C18.5), distal colon (C18.6-C18.7), and rectum (C19.9 and C20.9). Trends in age-standardized incidence rates (ASRs) were characterized by joinpoint regression analysis. A total of 303 802 CRC cases were analyzed. Overall, ASRs increased remarkably until 1993, with an annual percentage change (APC) of 4.9%, and then stabilized thereafter. By subsite, however, ASRs of proximal colon significantly increased, with APCs of 7.1% (1978-1991), 3.8% (1991-1996), and 0.9% (1996-2004); distal colon showed an initial significant increase, with an APC of 7.6%, but stabilized from 1991 until the end of observation; and rectal cancer showed an initial significant increase, with APCs of 1.9% (1978-1988) and 5.6% (1988-1992), but then decreased abruptly in 1992, the year CRC screening was introduced nationwide, with an APC of -1.0%. Thus, we revealed that changes in incidence trends for the three anatomic sites apparently began to differ in the 1990s. Careful monitoring is necessary to confirm whether these trends are changing in the Japanese population.

Effects of self-reported calorie restriction on correlations between SIRT1 polymorphisms and body mass index and long-term weight change.

SIRT1 acts as a cellular sensor to detect energy availability and modulates fat and glucose metabolism. This study assessed the effects of self-reported calorie restriction (CR) and exercise on correlations between SIRT1 polymorphisms and body mass index (BMI) and long-term weight change. This cross-sectional study enrolled 4023 subjects aged 35-69years (1847 men and 2176 women) selected from participants in the Japan Multi-Institutional Collaborative Cohort Study. This study was based on a self-administered questionnaire. No significant correlations between SIRT1 polymorphisms and BMI or long-term weight change were found in either the CR or the active groups. In the no-CR group, women with the rs1467568 G allele had a higher BMI than women without (p=0.02). Moreover, women with the rs7895833 A or rs1467568 G allele gained more weight from the age of 20years than women without these alleles (p=0.03 for rs7895833 and p=0.003 for rs1467568). In addition, the odds ratios (95% confidence intervals) of these alleles for overweight (BMI >27.5kg/m2) were significantly high in the no-CR women group (1.78 (1.06-2.99) for rs7895833 and 1.88 (1.13-3.15) for rs1467568) but not in the CR group. The results of this study suggest that CR might override the genetic contributions of the SIRT1 rs7895833 A and rs1467568 G alleles to BMI and long-term weight change.

Associations between Dietary Patterns, ADRß2 Gln27Glu and ADRß3 Trp64Arg with Regard to Serum Triglyceride Levels: J-MICC Study.

Interactions between dietary patterns and 2 ß-adrenergic receptor (ADRß) gene polymorphisms (ADRß2 Gln27Glu and ADRß3 Trp64Arg) were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35-69 years) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRß3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01) were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01). However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55). Interactions between other dietary patterns and ADRß polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRß3 polymorphism modifies the effects of the bread pattern on triglyceride levels.

Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk.

The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk.