Evidence regarding stress as a risk factor for cancer onset is inconsistent. In this study, based on the Japan Public Health Center-based Prospective Study, we enrolled 101,708 participants aged ...40-69 years from 1990-1994. The self-reported perceived stress level was collected at baseline and updated through 5-year follow-up. The association between perceived stress and cancer risk was measured by Cox proportional hazards regression model, adjusted for all known confounders. During follow-up (mean = 17.8 years), we identified 17,161 cancer cases. We found no association between baseline perceived stress level and cancer incidence. However, by taking account of the dynamic changes in perceived stress, time-varying analyses revealed a slightly (4-6%) increased overall cancer risk for subjects under elevated perceived stress levels compared to the 'low stress level' group. Analyses concerning long-term perceived stress level showed that individuals with constantly high perceived stress level had an 11% (95% confidence interval 1-22%) excess risk for cancer compared to subjects with persistently low stress levels. This association was confined to men (20% excess risk), and was particularly strong among smokers, alcohol drinkers, obese subjects, and subjects without family history of cancer. Therefore, we concluded high perceived stress level might contribute to excess overall cancer incidence among men.
We investigated the association between reproductive history and mortality from all and major causes among Japanese women.
A large-scale population-based cohort study in Japan included 40,149 ...eligible women aged 40–69 years in 1990–1994. A total of 4788 deaths were reported during follow-up (average 20.9 years). A Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CI) for all-cause and major causes of mortality, adjusting for potential confounders.
Inverse associations with all-cause mortality were found in parous women (0.74 0.67–0.82), women with two or three births compared with a single birth (2 births: 0.88 0.78–0.99; 3 births: 0.83 0.74–0.94), parous women who breastfed (0.81 0.75–0.87), women who were older at menopause (0.88 0.80–0.97; p-trend: <0.01), and women who had a longer fertility span (0.85 0.76–0.95; p-trend: <0.01). A positive association was seen between all-cause mortality and later age at first birth (≥30 years) than early childbearing (≤22 years).
Our study suggests that parous, two or three births, breastfeeding, late age at menopause, and longer reproductive span are associated with lower risk of all-cause of mortality.
•BMI ≥ 27 kg/m2 was associated with increased gastric cancer risk among men.•U-shaped increase in the risk was observed for proximal gastric cancer.•With H. pylori infection, BMI ≥ 27 kg/m2 increased ...proximal gastric cancer risk.
Body fatness and weight gain are considered probable causes of gastric cancer, specifically in the cardia region. However, limited evidence is available in Asia, where the burden of gastric cancer is high. The objective of this study was to determine an association between body-mass index (BMI) and gastric cancer risk using a large population prospective cohort.
92,056 subjects enrolled in the Japan Public Health Center-based prospective Study who reported their height and weight were followed up until the end of 2013. A Cox proportional hazards model was used to estimate the risk for gastric cancer and its subsite based on baseline BMI. A subgroup analysis was conducted taking account of Helicobacter pylori (H. pylori) infection and atrophic gastritis status.
2,860 gastric cancer cases (2,047 men, 813 women), 307 proximal gastric cancer cases (244 men, 63 women), and 1967 distal gastric cancer cases (1,405 men, 562 women) were found during the follow-up period. Among men, baseline BMI ≥ 27 kg/m2 increased the risk of overall gastric cancer (hazards ratio (HR) 1.23, 95% confidence interval (CI) 1.00–1.53). For both sexes, U-shaped increase in the risk was observed for proximal gastric cancer. Subgroup analysis showed a statistically significant association between the risk of proximal gastric cancer and BMI ≥ 27 kg/m2 among those who were atrophic gastritis positive, H. pylori antibody positive, and those who tested positive to either or both atrophic gastritis and H. pylori antibody.
Our result suggests that gastric cancer risk increases for men with BMI ≥ 27 kg/m2.
To elucidate the individual impacts of insulin and blood glucose on cancer risk, we investigated the association of plasma C‐peptide, a surrogated marker of insulin and glycated albumin (GA), a more ...stable marker of blood glucose, with all‐site and site‐specific cancer risk by mutually accounting for their confounding effects. The study was prospectively conducted with nearly 4,000 cancer cases arising in our population‐based cohort of 33,736 subjects who answered the baseline questionnaire and supplied blood samples. After exclusion of subjects with apparent DM, analysis was done in 3,036 cancer cases and 3,667 subcohort subjects. Among men and women combined, highest levels of C‐peptide were statistically significantly associated with an increased risk of all‐site Hazard ratio (HR): 1.21; 95% confidence interval: 1.02–1.42, colon 1.73; 1.20–2.47, liver 3.23; 1.76–5.91, kidney, renal pelvis and ureter cancers 2.47; 1.07–5.69, compared to the respective lowest levels, after adjustment for GA levels. Among these C‐peptide‐related cancers, colon and liver cancers also showed an increased risk associated with elevated GA levels independently of C‐peptide levels. The corresponding HRs for colon and liver cancers compared to the highest and lowest GA levels were 1.43 1.02–2.00 and 2.02 1.15–3.55, respectively. Effect modification by gender was only evident for the association between C‐peptide and colon cancer (p for interaction = 0.04). Higher insulin levels, independently of higher blood glucose levels, may be relevant to DM‐related carcinogenesis for several cancer sites. Examination of circulating insulin levels is a plausible option in evaluating cancer risk even in individuals who have not developed DM.
What's new?
While diabetes mellitus (DM) is associated with an increased cancer risk, carcinogenesis may not be explained by the influence of higher blood glucose levels only. This prospective case‐cohort study shows that higher levels of surrogate insulin marker C‐peptide are significantly associated with an increased risk of all‐site, colon, liver, kidney, renal pelvis, and ureter cancers after adjustment for blood glucose levels. (Colon and liver cancers also showed an increased risk associated with elevated blood glucose levels independently of C‐peptide levels.) Higher insulin levels, independently of higher blood glucose levels, may thus be relevant to DM‐related carcinogenesis for several cancer sites.
Cytochrome P450 (CYP) 1A1 and glutathione S‐transferases (GST) M1 and T1 are major enzymes in the carcinogen metabolizing pathway. We examined the association between single nucleotide polymorphisms ...(SNPs) of CYP1A1 (rs4646421, rs4646422 and rs1048943), GSTM1 and GSTT1 and gastric cancer risk in Japan. This is a nested case–control study (457 cases and 457 matched controls) of our population‐based cohort involving 36,745 subjects who answered a baseline questionnaire and supplied blood samples. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression models. We found that CYP1A1 (rs4646422) variant allele was associated with a statistically significant increased risk of gastric cancer compared with the homozygous wild‐type genotype (OR = 1.65; 95% CI = 1.17–2.32). GSTM1 null, GSTT1 null and GSTM1/T1 both or either null genotypes were associated with increased risk, but not statistically significantly. Combination of the CYP1A1 (rs4646422) variant allele and GSTM1/T1 both or either null genotypes was associated with a statistically significant increased risk compared with the combination of the CYP1A1 homozygous wild‐type genotype and the GSTM1/T1 both active genotypes. In addition, compared with CYP1A1 (rs4646422) homozygous wild‐type genotypes in those who were never‐smokers, CYP1A1 variant alleles in those who smoked ≥30 pack‐years were associated with an increased risk; neither gene–gene nor gene–environment interactions were significant. The CYP1A1 (rs4646422) polymorphism might be involved in gastric carcinogenesis among the Japanese population.
What's new?
The study of association between CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and gastric cancer risk was done in recent several meta‐analyses. However, most individual studies are retrospective, and their sample sizes are small. Although neither gene–gene nor gene–environment interactions were significant, the CYP1A1 (rs4646422) polymorphism might be involved in gastric carcinogenesis among the Japanese population.
The association between alcohol intake and colorectal cancer (CRC) may vary secondary to single nucleotide polymorphisms (SNPs) in two pathways related to alcohol intake. 375 cases of CRC were ...identified among 38 373 Japan Public Health Center-based prospective Study (JPHC Study) participants who had returned a baseline questionnaire, reported no diagnosis of any cancer and provided blood samples. For each case, two controls were selected on matching variables. Logistic regression models were used to determine matched Odds Ratios (OR) and 95% Confidence Intervals (CI) for the association between alcohol consumption, genetic polymorphisms of enzymes in the alcohol- and folate metabolic pathways (e.g. methylenetetrahydrofolate reductase (MTHFR) rs1801133) and CRC risk. Compared to never/occasional alcohol intake, moderate to heavy alcohol intake was associated with CRC (OR = 2.12, 95% CI, 1.34-3.36). When compared to the CC genotype, the MTHFR rs1801133 CT/TT genotype was inversely associated with CRC (OR = 0.72, 95% CI, 0.54-0.97). Never/occasional consumers of alcohol with the MTHFR rs1801133 CT/TT genotype were also at a reduced risk of CRC compared to never/occasional drinkers with the CC genotype (OR = 0.68, 95% CI, 0.47-0.98) (P for interaction = 0.27). The results indicate that the folate pathway is likely to be involved in alcohol-related CRC development.
The influence of body mass index (BMI) change during adulthood on the development of oesophageal squamous-cell carcinoma (ESCC) is unknown.
Based on the Japan Public Health Center-based Prospective ...Study, we enrolled 103 238 participants from 1990 to 1994. Anthropometric data at age 20 years, baseline, and 5- and/or 10-year follow-up surveys were collected by questionnaire. The effect of BMI change between age 20 years and baseline on ESCC risk was estimated by Cox proportional hazards regression models. The updated BMI was taken into account by fitting a simple linear regression model for each individual, where the slope was incorporated into regressions as a time-varying variable.
After excluding the first 5 years of observation, we identified 342 newly diagnosed ESCC cases. An increase in BMI during adulthood was linked with a decreased risk of ESCC development, with each 1% increase per 5 years corresponding to a 15% decrease in ESCC risk (95% confidence interval 9-21%). Identical estimates were obtained from time-dependent models. The importance of BMI change was not modified by gender, smoking, or alcohol drinking but confined to participants assessed as non-overweight at baseline.
An increase in BMI during adulthood is associated with a lower risk of developing ESCC among non-overweight subjects.
This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric ...cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls.
A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer.
Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only.
These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.
The association between sleep and stress and cancer is underinvestigated. We evaluated these factors in association with gastric cancer (GC). Five case-control studies from the Stomach Cancer Pooling ...(StoP) Project were included. We calculated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for sleep duration and stress level in association with GC through multiple logistic regression models adjusted for several lifestyle factors. The analysis included 1293 cases and 4439 controls, 215 cardia and 919 noncardia GC, and 353 diffuse and 619 intestinal types. Sleep duration of ≥9 h was associated with GC (OR =1.57, 95% CI = 1.23–2.00) compared to 8 h. This was confirmed when stratifying by subsite (noncardia OR = 1.59, 95% CI = 1.22–2.08, and cardia OR = 1.63, 95% CI = 0.97–2.72) and histological type (diffuse OR = 1.65, 95% CI = 1.14–2.40 and intestinal OR = 1.24, 95% CI = 0.91–1.67). Stress was associated with GC (OR = 1.33, 95% CI = 1.18–1.50, continuous). This relationship was selectively related to noncardia GC (OR = 1.28, 95% 1.12–1.46, continuous). The risk of diffuse (OR = 1.32, 95% CI = 1.11–1.58) and intestinal type (OR = 1.23, 95% CI = 1.07–1.42) were higher when stress was reported. Results for the association between increasing level of stress and GC were heterogeneous by smoking and socioeconomic status (p for heterogeneity = 0.02 and <0.001, respectively). In conclusion, long sleep duration (≥9 h) was associated with GC and its subtype categories. Stress linearly increased the risk of GC and was related to noncardia GC.
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