AbstractObjectiveTo evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort ...study.DesignNested case-cohort study within the Japan Public Health Center-based Prospective Study cohort.SettingNine public health centre areas across Japan.Participants3301 incident cases of cancer and 4044 randomly selected subcohort participants.ExposurePlasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay. Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts. Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration, with the lowest quarter as the reference.Main outcome measureIncidence of overall or site specific cancer.ResultsPlasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). Among the findings for cancers at specific sites, an inverse association was found for liver cancer, with corresponding hazard ratios of 0.70 (0.44 to 1.13), 0.65 (0.40 to 1.06), and 0.45 (0.26 to 0.79) (P for trend=0.006). A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios.ConclusionsIn this large prospective study, higher vitamin D concentration was associated with lower risk of total cancer. These findings support the hypothesis that vitamin D has protective effects against cancers at many sites.
Helicobacter pylori (H. pylori), an established risk factor for gastric cancer, is suggested to also play a role in the development of pancreatic cancer; however, the association remains ...inconclusive. We examined this association among Japanese men and women. H. pylori and atrophic gastritis (AG) status were determined serologically, using blood sample collected during health checkups. A total of 20,116 subjects enrolled in the Japan Public Health Center-based Prospective Study Cohort II with available data on H. pylori seropositivity (anti-H. pylori) and AG were followed until the end of 2010. Cox proportional hazards models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI), using the information from the baseline survey. During 320,470 person-years of follow-up, 119 cases of pancreatic cancer were identified. No statically significant increase or decrease in pancreatic cancer risk was observed for H. pylori and AG status, independently or in combination. In a multivariable-adjusted model, we observed a non-significant decrease in the risk among those who had AG but were anti-H. pylori seronegative (HR 0.57, 95% CI 0.31-1.03). In a stratified analysis, we observed a statistically significant increased risk of pancreatic cancer for AG+ (HR 3.64, 95% CI 1.37-9.66), and AG+/anti-H. pylori- or AG+/anti-H. pylori+ (HR 5.21, 95% CI 1.14-23.87) among current smokers. Non-smokers in all categories of AG and anti-H. pylori showed a non-statistical decrease in the risk. There was no statistically significant interaction between H. pylori infection, AG status, and smoking status. Our findings suggest H. pylori seropositivity and AG, individually or in combination, are not associated with the risk of pancreatic cancer in a general Japanese population. Among current smokers, pancreatic cancer risk increased with AG, regardless of H. pylori infection status.
Background: A high body mass index (BMI) has been proposed as an important risk factor for pancreatic cancer. However, this association of BMI with pancreatic cancer risk has not been confirmed in ...Asian populations. Methods: We evaluated the association between BMI (either at baseline or during early adulthood) and pancreatic cancer risk by conducting a pooled analysis of nine population-based prospective cohort studies in Japan with more than 340,000 subjects. Summary hazard ratios (HRs) were estimated by pooling study-specific HRs for unified BMI categories with a random-effects model. Results: Among Japanese men, being obese at baseline was associated with a higher risk of pancreatic cancer incidence (≥30 kg/m2 compared with 23 to <25 kg/m2, adjusted HR 1.71; 95% confidence interval CI, 1.03–2.86). A J-shaped association between BMI during early adulthood and pancreatic cancer incidence was seen in men. In contrast, we observed no clear association among women, although there may be a positive linear association between BMI at baseline and the risk of pancreatic cancer (per 1 kg/m2, adjusted HR 1.02; 95% CI, 1.00–1.05). Conclusions: Pooling of data from cohort studies with a considerable number of Japanese subjects revealed a significant positive association between obesity and pancreatic cancer risk among men. This information indicates that strategies that effectively prevent obesity among men might lead to a reduced burden of pancreatic cancer, especially in Asian populations.
Family history (FH) of cancer is an important factor of increased risk of several cancers. Although the association between FH of cancer and concordant cancer risk has been reported in many previous ...epidemiological studies, no comprehensive prospective study with adjustment for lifestyle habits has evaluated the association of FH of cancer and concordant cancer risk. We investigated the association between FH of cancer and concordant cancer risk in a Japanese population‐based prospective study, initiated in 1990 for cohort I and in 1993 for cohort II. We analyzed data on 103,707 eligible subjects without a history of cancer who responded to a self‐administered questionnaire including FH of cancer at baseline. Study subjects were followed through 2012 and analyzed using multivariable‐adjusted Cox proportional hazards regression models. During 1,802,581 person‐years of follow‐up, a total of 16,336 newly diagnosed cancers were identified. Any site (Hazard ratios = 1.11 (95% confidence interval = 1.07–1.15), esophagus (2.11 1.00–4.45), stomach (1.36 1.19–1.55), liver (1.69 1.10–2.61), pancreas (2.63 1.45–4.79), lung (1.51 1.14–2.00), uterus (1.93 1.06–3.51) and bladder cancers (6.06 2.49–14.74) with FH of the concordant cancer were associated with an increased risk compared to those without FH. Our findings suggest that having FH of cancer is associated with an increased risk of several concordant cancer incidences in an Asian population. Enquiring about FH of several types of cancer may be important in identifying groups at high‐risk of those cancers.
What's new?
Although many epidemiological studies have reported an association between family history of cancer and concordant cancer risk, the association has not been evaluated in a comprehensive prospective study with adjustment for lifestyle habits. We found that a family history of cancer is associated with increased risk in the incidence of several concordant cancers in an Asian population.
Most previous prospective studies in Western countries found no association between consumption of fish and n-3 (ω-3) polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA), ...docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), for which the main source is fish, and pancreatic cancer risk. However, prospective evidence is still lacking among populations who have a relatively higher fish consumption.
We investigated the association between fish and n-3 PUFA consumption and pancreatic cancer risk in a population-based, prospective study in Japanese men and women.
The Japan Public Health Center-based Prospective Study (JPHC study) has enrolled 140,420 subjects. We analyzed data on 82,024 eligible participants aged 45-74 y without a history of cancer who responded to a validated food-frequency questionnaire that included 138 items in 1995 for cohort I and in 1998 for cohort II. Participants were followed through 2010. HRs and corresponding 95% CIs for the highest compared with lowest quartile were calculated by using multivariable-adjusted Cox proportional hazards regression models.
During 1,068,774 person-years of follow-up, 449 newly diagnosed pancreatic cancers were identified. After the exclusion of pancreatic cancer cases in the first 3 y of follow-up, we found an inverse association of marine n-3 PUFA (EPA+DPA+DHA) and DHA consumption with pancreatic cancer risk: compared with the lowest quartile, multivariate-adjusted HRs in the highest quartile were 0.70 (95% CI: 0.51, 0.95; P-trend = 0.07) and 0.69 (0.51, 0.94; P-trend = 0.03), respectively. Associations for total fish, n-3 PUFA, EPA, and DPA consumption were similar but were not significant.
High n-3 PUFA, especially marine n-3 PUFAs, and DHA consumption was associated with a lower risk of pancreatic cancer in a population with a large variation in fish consumption, although the data apply to only a portion of the JPHC study subjects.
Detailed prospective evaluation of cigarette smoking associated with pancreatic cancer risk in large Asian populations is limited. The aim of this study was to examine this association in a Japanese ...population, with a particular focus on evaluating sex differences.
We performed a pooled analysis of 10 population-based cohort studies. We calculated study-specific HRs and 95% confidence intervals (CI) using Cox proportional hazards regression, and then estimated summary HRs by pooling these estimates with a random effects model.
During 4,695,593 person-years of follow-up in 354,154 participants, 1,779 incident pancreatic cancer cases were identified. We observed an increased pancreatic cancer risk for current smoking compared with never smoking in both males HR (95% CI), 1.59 (1.32-1.91) and females HR (95% CI), 1.81 (1.43-2.30). Significant risk elevations for former smoking and small cumulative dose of ≤20 pack-years (PY) were observed only among females, regardless of environmental tobacco smoke exposure. Trend analysis indicated significant 6% and nonsignificant 6% increases in pancreatic cancer risk for every 10 PYs in males and females, respectively. Risk became comparable with never smokers after 5 years of smoking cessation in males. In females, however, we observed no risk attenuation by smoking cessation.
This study supports the well-known association between smoking and pancreatic cancer and indicates potential sex differences in a Japanese population. Quitting smoking would be beneficial for pancreatic cancer prevention, especially in males.
Pancreatic cancer risk is increased with cumulative smoking exposure and decreased with smoking cessation, with potential sex differences.
Few prospective studies have investigated the etiology of brain tumor, especially among Asian populations. Both coffee and green tea are popular beverages, but their relation with brain tumor risk, ...particularly with glioma, has been inconsistent in epidemiological studies. In this study, we evaluated the association between coffee and greed tea intake and brain tumor risk in a Japanese population. We evaluated a cohort of 106,324 subjects (50,438 men and 55,886 women) in the Japan Public Health Center‐Based Prospective Study (JPHC Study). Subjects were followed from 1990 for Cohort I and 1993 for Cohort II until December 31, 2012. One hundred and fifty‐seven (70 men and 87 women) newly diagnosed cases of brain tumor were identified during the study period. Hazard ratio (HR) and 95% confidence intervals (95%CIs) for the association between coffee or green tea consumption and brain tumor risk were assessed using a Cox proportional hazards regression model. We found a significant inverse association between coffee consumption and brain tumor risk in both total subjects (≥3 cups/day; HR = 0.47, 95%CI = 0.22–0.98) and in women (≥3 cups/day; HR = 0.24, 95%CI = 0.06–0.99), although the number of cases in the highest category was small. Furthermore, glioma risk tended to decrease with higher coffee consumption (≥3 cups/day; HR = 0.54, 95%CI = 0.16–1.80). No association was seen between green tea and brain tumor risk. In conclusion, our study suggested that coffee consumption might reduce the risk of brain tumor, including that of glioma, in the Japanese population.
What's new?
How do coffee and green tea affect risk of brain tumor? Previous studies have yielded conflicting results. In this paper, the authors investigated the effects of both beverages in a Japanese population. They collected data from more than 100,000 subjects enrolled in the Japanese Public Health Center‐Based Prospective Study covering a period of 22 years. Their analysis suggests that drinking more than three cups of coffee per day reduced risk of brain tumor, including glioma—although few participants drank that much coffee. Green tea consumption, they found, did not affect brain cancer risk.
Evidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and ...gastric cancer in the Stomach cancer Pooling (StoP) Project consortium.
A total of 9438 cases and 20,451 controls from 22 studies worldwide were included. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer for regular versus non-regular tea drinkers were estimated by one and two-stage modelling analyses, including terms for sex, age and the main recognised risk factors for gastric cancer.
Compared to non-regular drinkers, the estimated adjusted pooled OR for regular tea drinkers was 0.91 (95% CI: 0.85-0.97). When the amount of tea consumed was considered, the OR for consumption of 1-2 cups/day was 1.01 (95% CI: 0.94-1.09) and for >3 cups/day was 0.91 (95% CI: 0.80-1.03). Stronger inverse associations emerged among regular drinkers in China and Japan (OR: 0.67, 95% CI: 0.49-0.91) where green tea is consumed, in subjects with H. pylori infection (OR: 0.68, 95% CI: 0.58-0.80), and for gastric cardia cancer (OR: 0.64, 95% CI: 0.49-0.84).
Our results indicate a weak inverse association between tea consumption and gastric cancer.
Discovery of a high‐risk group for pancreatic cancer is important for prevention of pancreatic cancer. The present study was conducted as a nested case‐control study including 170 pancreatic cancer ...cases and 340 matched controls of our population‐based cohort study involving 30 239 subjects who answered a baseline questionnaire and supplied blood samples. Twelve targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were calculated using conditional logistic regression models. Statistically significant P‐value was defined as P < .05. Increasing 1,5‐anhydro‐d‐glucitol (1,5‐AG) levels were associated with a decreasing trend in pancreatic cancer risk (OR of quartile 4 Q4, 0.50; 95% CI, 0.27‐0.93; P = .02). Increasing methionine levels were also associated with an increasing trend of pancreatic cancer risk (OR of Q4, 1.79; 95% CI, 0.94‐3.40: P = .03). Additional adjustment for potential confounders attenuated the observed associations of 1,5‐AG and methionine (P for trend = .06 and .07, respectively). Comparing subjects diagnosed in the first 0‐6 years, higher levels of 1,5‐AG, asparagine, tyrosine and uric acid showed a decreasing trend for pancreatic cancer risk (P for trend = .04, .04, .04 and .02, respectively), even after adjustment for potential confounders. We found that the 12 target metabolites were not associated with pancreatic cancer risk. However, metabolic changes in the subjects diagnosed in the first 0‐6 years showed a similar tendency to our previous reports. These results might suggest that these metabolites are useful for early detection but not for prediction of pancreatic cancer.
We analyzed targeted blood metabolites quantitatively by gas chromatography/tandem mass spectrometry in a nested case‐control study including 170 pancreatic cancer cases and 340 matched controls. We found that some metabolites are useful for early detection of pancreatic cancer but are not associated with the risk of pancreatic cancer.
To date, the association between diabetes mellitus (DM) and gastric cancer has been controversial, including the underlying mechanism. We investigated the association between plasma diabetic ...biomarkers (insulin, C‐peptide, and blood glucose) and gastric cancer risk. In addition, homeostasis model assessment of insulin resistance (HOMA‐IR) and homeostasis model assessment of β‐cell function (HOMA‐β) were calculated. A total of 36,745 subjects aged 40–69 years in the Japan Public Health Center‐based prospective study (JPHC) who returned the baseline questionnaire and provided blood samples were followed from 1990 to 2004. In the present analysis, 477 cases and 477 matched controls were used. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for developing gastric cancer were calculated using conditional logistic regression models. Plasma insulin was positively associated with increased risk of gastric cancer; compared to tertile 1, ORs were 1.69 (95% CI = 1.11–2.59) and 2.01 (1.19–3.38) for tertiles 2 and 3, respectively (p for trend = 0.009). In men, C‐peptide was also positively associated with a significant risk; corresponding ORs were 1.42 (0.85–2.38) and 1.91 (1.03–3.54), respectively (p for trend = 0.04). These findings were confirmed for blood samples from the fasting group (≥8 hr after a meal). Higher HOMA‐IR was also associated with increased risk, whereas no association was observed for blood glucose. Our findings suggest that Japanese population with higher insulin and C‐peptide levels derived from insulin resistance have an elevated risk of gastric cancer.
What's new?
The idea that diabetes mellitus may play a role in some instances of gastric carcinogenesis is intriguing but controversial. Here, a positive association was identified for gastric cancer risk and plasma insulin levels, based on investigation of plasma biomarkers in a Japanese study population. The association was evident for measures of homeostasis model assessment of insulin resistance (HOMA‐IR). By contrast, no association was found for blood glucose levels. The results suggest that hyperinsulinemia derived from insulin resistance, rather than hyperglycemia, is important in gastric carcinogenesis.
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