Personalized approaches to prevention based on genetic risk models have been anticipated, and many models for the prediction of individual breast cancer risk have been developed. However, few studies have evaluated personalized risk using both genetic and environmental factors. We developed a risk model using genetic and environmental risk factors using 1319 breast cancer cases and 2094 controls from three case–control studies in Japan. Risk groups were defined based on the number of risk alleles for 14 breast cancer susceptibility loci, namely low (0–10 alleles), moderate (11–16) and high (17+). Environmental risk factors were collected using a self-administered questionnaire and implemented with harmonization. Odds ratio (OR) and C-statistics, calculated using a logistic regression model, were used to evaluate breast cancer susceptibility and model performance. Respective breast cancer ORs in the moderate- and high-risk groups were 1.69 (95% confidence interval, 1.39–2.04) and 3.27 (2.46–4.34) compared with the low-risk group. The C-statistic for the environmental model of 0.616 (0.596–0.636) was significantly improved by combination with the genetic model, to 0.659 (0.640–0.678). This combined genetic and environmental risk model may be suitable for the stratification of individuals by breast cancer risk. New approaches to breast cancer prevention using the model are warranted.
Background Health effects of multiple role occupancy and their mechanism are not fully addressed. We examined (1) the association between the number of social roles and self-rated health (SRH) and (2) the mediation effects of ikigai (the sense of life worth living) and the size of close social networks to the association. Methods We analysed the cross-sectional baseline questionnaire data of the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT) of 22 180 men and 26 616 women in age 40–59 years. The independent variable was the number of social roles, counting five social roles as a spouse, parent, child, worker and a role in a community. The dependent variable was poor SRH. Logistic regression was used to estimate the ORs for poor SRH by the number of social roles and to test linear trends. Mediation analyses were conducted to estimate the proportion mediated by ikigai and the size of close social networks. Results Compared with people with 0–1 social role, those who had two or more roles had a lower OR of poor SRH in both men and women. There was a linear inverse trend in the association; people having the largest (5) versus lowest (0–1) number of social roles had the lowest ORs: 0.55 (95% CI 0.46 to 0.66) in men and 0.72 (95% CI 0.61 to 0.86) in women. The estimated proportion mediated by ikigai was over 50%, whereas the size of close social networks mediated the association by approximately 20%. Conclusion An inverse association between the number of social roles and poor SRH and mediation effects of ikigai and the size of close social networks were identified. Having even one more social role might benefit subjective health via increased ikigai and the size of close social networks.
The association of serum liver enzyme levels with all-cause mortality in individuals without hepatitis B virus or hepatitis C virus infection is inconsistent. We aimed to investigate all-cause and non-liver disease mortality according to levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) stratified by hepatitis virus infection status in a Japanese cohort.Participants were 7243 men and 13 513 women aged 40-69 years at the baseline survey in 1993-1994. Multivariate-adjusted hazard ratios of death from the baseline health check-up to December 2012 were calculated with a Cox proportional hazards model controlling for potential confounding factors.During follow-up, 2235 deaths in men and 1901 deaths in women were identified. All serum liver enzymes were associated with all-cause mortality in each sex and hepatitis virus infection status. In participants without infection, those with more than twice the upper level of normal (ULN), which was defined as 30 IU/L for AST and ALT and 50 IU/L for GGT, had a higher risk of non-liver disease mortality compared to those below the ULN (HR 1.69; 95% confidence interval 1.13-2.53, 1.49; 1.02-2.18, 1.39; 1.11-1.73, 1.72; 1.08-2.74 and 1.72; 1.10-2.69 for AST, ALT, and GGT in men and AST and GGT in women, respectively), except for ALT in women.In participants without hepatitis virus infection, serum liver enzyme levels were positively associated with all-cause mortality. Similar associations were also found for non-liver disease mortality.
Gastric carcinogenesis may be under the combined influence of factors related to the host, Helicobacter pylori bacterial virulence and the environment. One possible host-related factor is the inflammatory or immune response. To clarify this point, we investigated the association between plasma levels of C-reactive protein (CRP) and serum amyloid A (SAA) and the subsequent risk of gastric cancer in a population-based nested case-control study. Subjects were observed from 1990 to 2004. Among 36 745 subjects who answered the baseline questionnaire and provided blood samples, 494 gastric cancer cases were identified and matched to 494 controls for our analysis. The overall distribution of CRP and SAA was not apparently associated with the development of gastric cancer. However, a statistically significant increased risk was observed when subjects were categorized dichotomously. The adjusted odds ratio (OR) for the development of gastric cancer for the CRP-positive group (CRP > 0.18 mg/dl) compared with the CRP-negative group was 1.90 [95% confidence interval (CI): 1.19-3.02, P = 0.007]. The OR for the SAA-positive group (SAA > 8 mug/ml) compared with the SAA-negative group was 1.93 (95% CI: 1.22-3.07, P = 0.005). In conclusion, our results suggest that those who react strongly to inflammation or who have a high host immune response, as reflected by extremely elevated plasma levels of CRP and SAA, are at a high risk to develop gastric cancer.
Using Food Frequency Questionnaires (FFQs) to compare dietary references for screening has been in high demand. However, FFQs have been widely used for ranking individuals in a population based on their dietary intake. We determined the validity of sodium (salt equivalent) intake, potassium intake, and sodium-to-potassium (Na/K) ratio obtained using the FFQ for identifying individuals who deviated from the dietary reference intakes (DRIs) measured using multiple 24-h urinary excretion measurements or 12-day weighed food records (WFR). This study included 235 middle-aged subjects. The correlation coefficients (CCs) between the FFQ and WFR estimates were mostly moderate (0.24−0.54); the CCs between the FFQ and 24-h urinary excretion measurements were low or moderate (0.26−0.38). Values of area under the receiver-operating curve (AUC) at the point of DRIs for salt equivalent or potassium were >0.7 with the WFR as the reference standard and 0.60−0.76 with the 24-h urinary excretion as the reference standard. Using both standard measures, the AUC for the Na/K ratio was <0.7. The accuracy of salt equivalent and potassium intake estimation using the FFQ to determine absolute intake point was comparable to that using WFR, allowing for quantified error, but not as good as that of 24-h urinary excretion.
Smoking and alcohol are established risk factors for several types of cancer, but the effects on biliary cancers, comprising biliary tract cancer (BTC) and intrahepatic bile duct cancer (IHBDC), have been inconclusive.
Sex hormones, particularly androgens, have been implicated in prostate carcinogenesis. Overall, however, prospective studies have reported no association between circulating levels of sex hormones and the risk of prostate cancer. However, despite the possible difference in the effects of hormones on prostate cancer risk by stage, age, body mass index (BMI) and isoflavones, evidence for these is sparse. Moreover, few studies have been conducted in Asian populations, who are relatively lean and have high isoflavone consumption. We examined the hypothesis that plasma concentrations of circulating testosterone and sex hormone-binding globulin (SHBG) are associated with the risk of prostate cancer in a case-control study nested in the Japan Public Health Center-based Prospective Study. Concentrations of total testosterone and SHBG were measured in plasma samples from 201 patients with prostate cancer and 402 matched control participants, and concentrations of free testosterone were calculated. No overall association between the plasma levels of any hormone and total prostate cancer was observed. Odds ratios (95% confidence interval [CI]) in the highest versus lowest group were 0.71 (95% CI = 0.36-1.41, Ptrend = 0.43) for total testosterone, 0.70 (95% CI = 0.39-1.27, Ptrend = 0.08) for free testosterone and 1.38 (95% CI = 0.69-2.77, Ptrend = 0.23) for SHBG. When stratified by cancer stage, age, BMI and plasma isoflavone level, free testosterone was inversely associated with localized cancers and equol producers, while SHBG was associated with an increased risk of prostate cancer in younger men. In conclusion, in this nested case-control study, concentrations of circulating total testosterone, free testosterone or SHBG were not strongly associated with a risk for total prostate cancer.
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