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Although the impact of tobacco consumption on the occurrence of lung cancer is well-established, risk estimation could be improved by risk prediction models that consider various smoking habits, such as quantity, duration, and time since quitting. We constructed a risk prediction model using a population of 59 161 individuals from the Japan Public Health Center (JPHC) Study Cohort II. A parametric survival model was used to assess the impact of age, gender, and smoking-related factors (cumulative smoking intensity measured in pack-years, age at initiation, and time since cessation). Ten-year cumulative probability of lung cancer occurrence estimates were calculated with consideration of the competing risk of death from other causes. Finally, the model was externally validated using 47 501 individuals from JPHC Study Cohort I. A total of 1210 cases of lung cancer occurred during 986 408 person-years of follow-up. We found a dose-dependent effect of tobacco consumption with hazard ratios for current smokers ranging from 3.78 (2.00-7.16) for cumulative consumption ≤15 pack-years to 15.80 (9.67-25.79) for >75 pack-years. Risk decreased with time since cessation. Ten-year cumulative probability of lung cancer occurrence estimates ranged from 0.04% to 11.14% in men and 0.07% to 6.55% in women. The model showed good predictive performance regarding discrimination (cross-validated c-index = 0.793) and calibration (cross-validated χ 2 = 6.60; P-value = .58). The model still showed good discrimination in the external validation population (c-index = 0.772). In conclusion, we developed a prediction model to estimate the probability of developing lung cancer based on age, gender, and tobacco consumption. This model appears useful in encouraging high-risk individuals to quit smoking and undergo increased surveillance., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Diabetes mellitus constitutes a major disease burden globally, and the prevalence of diabetes continues to increase worldwide. We aimed to estimate the burden of cancer associated with type 2 diabetes mellitus in Japan between 2010 and 2030. In this study, we estimated the population attributable fraction of cancer risk associated with type 2 diabetes in 2010 and 2030 using the prevalence estimates of type 2 diabetes in Japan from 1990 to 2030, summary hazard ratios of diabetes and cancer risk from a pooled analysis of eight large-scale Japanese cohort studies, observed incidence/mortality of cancer in 2010 and predicted incidence/mortality for 2030 derived from the age-period-cohort model. Our results showed that between 2010 and 2030, the total numbers of cancer incidence and mortality were predicted to increase by 38.9% and 10.5% in adults aged above 20 years, respectively. In the number of excess incident cancer cases associated with type 2 diabetes, an increase of 26.5% in men and 53.2% in women is expected between 2010 and 2030. The age-specific analysis showed that the population attributable fraction of cancer will increase in adults aged >60 years over time, but will not change in adults aged 20-59 years. In conclusion, this study suggests a modest but steady increase in cancers associated with type 2 diabetes., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Green tea and coffee consumption may decrease the risk of some types of cancers. However, their effects on biliary tract cancer (BTC) have been poorly understood. In this population-based prospective cohort study in Japan, we investigated the association of green tea (total green tea, Sencha, and Bancha/Genmaicha) and coffee consumption with the risk for BTC and its subtypes, gallbladder cancer, and extrahepatic bile duct cancer. The hazard ratios and 95% confidence intervals were calculated using the Cox proportional hazard model. A total of 89 555 people aged 45-74 years were enrolled between 1995 and 1999 and followed up for 1 138 623 person-years until 2010, during which 284 cases of BTC were identified. Consumption of >720 mL/day green tea was significantly associated with decreased risk compared with consumption of ≤120 mL/day (hazard ratio = 0.67 [95% confidence interval, 0.46-0.97]), and a non-significant trend of decreased risk associated with increased consumption was observed (P-trend = 0.095). In the analysis according to the location of the primary tumor, consuming >120 mL green tea tended to be associated with decreased risk of gallbladder cancer and extrahepatic bile duct cancer. When Sencha and Bancha/Genmaicha were analyzed separately, we observed a non-significant trend of decreased risk of BTC associated with Sencha but no association with Bancha/Genmaicha. For coffee, there was no clear association with biliary tract, gallbladder, or extrahepatic bile duct cancer. Our findings suggest that high green tea consumption may lower the risk of BTC, and the effect may be attributable to Sencha consumption., (© 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

International reviews have concluded that consumption of fruit and vegetables might decrease the risk of lung cancer. However, the relevant epidemiological evidence still remains insufficient in Japan. Therefore, we performed a pooled analysis of data from four population-based cohort studies in Japan with >200 000 participants and >1700 lung cancer cases. We computed study-specific hazard ratios by quintiles of vegetable and fruit consumption as assessed by food frequency questionnaires. Summary hazard ratios were estimated by pooling the study-specific hazard ratios with a fixed-effect model. In men, we found inverse associations between fruit consumption and the age-adjusted and area-adjusted risk of mortality or incidence of lung cancer. However, the associations were largely attenuated after adjustment for smoking and energy intake. The significant decrease in risk among men remained only for a moderate level of fruit consumption; the lowest summary hazard ratios were found in the third quintile of intake (mortality: 0.71, 95% confidence interval 0.60-0.84; incidence: 0.83, 95% confidence interval 0.70-0.98). This decrease in risk was mainly detected in ever smokers. Conversely, vegetable intake was positively correlated with the risk of incidence of lung cancer after adjustment for smoking and energy intake in men (trend P, 0.024); the summary hazard ratio for the highest quintile was 1.26 (95% confidence interval 1.05-1.50). However, a similar association was not detected for mortality from lung cancer. In conclusion, a moderate level of fruit consumption is associated with a decreased risk of lung cancer in men among the Japanese population., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Although a growing body of evidence suggests a link between diabetes and cancer, it is not clear whether diabetes independently increases the risk of cancer. We conducted a comprehensive assessment of the association between pre-existing diabetes and total and site-specific cancer risk based on a pooled analysis of eight cohort studies in Japan (>330 000 subjects). We estimated a summary hazard ratio by pooling study-specific hazard ratios for total and site-specific cancer by using a random-effects model. A statistically increased risk was observed for cancers at specific sites, such as colon (hazard ratio; HR = 1.40), liver (HR = 1.97), pancreas (HR = 1.85) and bile duct (HR = 1.66; men only). Increased risk was also suggested for other sites, and diabetes mellitus was associated with an overall 20% increased risk in total cancer incidence in the Japanese population. The association between these two diseases has important implications for reiterating the importance of controlling lifestyle factors and may suggest a possible strategy for cancer screening among patients with diabetes. Studies continuously investigating the risk factors for diabetes are also important., (© 2013 Japanese Cancer Association.)

The development of a new plasma biomarker for early detection would be necessary to improve the overall outcome of colorectal cancer. Here we report the identification and validation of the ninth component of complement (C9) as a novel plasma biomarker for colorectal cancer by cutting-edge proteomic technologies. Plasma proteins were enzymatically digested into a large array of peptides, and the relative quantity of a total of 94,803 peptide peaks was compared between 31 colorectal cancer patients and 59 age/sex-matched healthy controls using 2D image-converted analysis of liquid chromatography and mass spectrometry. The selected biomarker candidates were validated in 345 subjects (115 colorectal cancer patients and 230 age/sex-matched healthy controls) using high-density reverse-phase protein microarrays. Plasma levels of Apo AI and C9 in colorectal cancer patients significantly differed from healthy controls with P values of 7.94×10(-4) and 1.43×10(-12) (Student's t-test), respectively. In particular, C9 was elevated in patients with colorectal cancer, including those with stage-I and -II diseases (P=3.01×10(-3) and P=1.13×10(-5) , respectively). Although the significance of the present study must be validated in an independent clinical study, the increment of plasma C9 may be applicable to the early detection of colorectal cancer., (© 2010 Japanese Cancer Association.)

Soy food is known to contribute greatly to a reduction in the risk of gastric cancer (GC). However, both Japanese and Korean populations have high incidence rates of GC despite the consumption of a wide variety of soy foods. One primary reason is that they consume fermented rather than non-fermented soy foods. In order to assess the varying effects of fermented and non-fermented soy intake on GC risk in these populations, we conducted a meta-analysis of published reports. Twenty studies assessing the effect of the consumption of fermented soy food on GC risk were included, and 17 studies assessing the effect of the consumption of non-fermented soy food on GC risk were included. We found that a high intake of fermented soy foods was significantly associated with an increased risk of GC (odds ratio [OR] = 1.22, 95% confidence interval [CI] = 1.02-1.44, I(2) = 71.48), whereas an increased intake of non-fermented soy foods was significantly associated with a decreased risk of GC (overall summary OR = 0.64, 95% CI = 0.54-0.77, I(2) = 64.27). These findings show that a high level of consumption of non-fermented soy foods, rather than fermented soy foods, is important in reducing GC risk., (© 2010 Japanese Cancer Association.)

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., (© 2010 Japanese Cancer Association.)

Coffee and caffeine consumption are thought to increase the risk of bladder cancer. However, few studies have stratified this risk by smoking status, which is a potential confounder. Here, we investigated the association between coffee, green tea (another major source of caffeine), and caffeine, and bladder cancer incidence in relation to smoking status. We conducted a population-based prospective study in a cohort of Japanese, comprising a total of 49 566 men and 54 874 women aged 40–69 years who reported their coffee and green tea consumption at baseline. During follow-up from 1990 through 2005, 164 men and 42 women were newly diagnosed with bladder cancer. Cigarette smoking was associated with an increased risk of bladder cancer, with a strong dose–response relationship. Coffee was positively associated with bladder cancer risk in men, without statistical significance. When stratified by smoking status, coffee and caffeine consumption were associated with an increased risk of bladder cancer in never- or former-smoking men, with hazard ratios (95% confidence interval) in the highest categories of coffee (one or more cups per day) and caffeine consumption compared with the lowest of 2.24 (95% CI = 1.21–4.16) and 2.05 (95% CI = 1.15–3.66), respectively. In conclusion, cigarette smoking was confirmed as a risk factor for bladder cancer. Coffee and caffeine may be associated with an increased bladder cancer risk in never or former smokers among Japanese men.

Although Helicobacter pylori (H. pylori ) infection is considered a key risk factor for atrophic gastritis, along with other environmental factors, it is still unclear which factor is involved in the development of atrophic gastritis among H. pylori-infected subjects. In the present cross-sectional study, therefore, we analyzed various dietary factors in relation to the presence of atrophic gastritis among H. pylori-infected subjects who participated in a health check-up program in a town in northeastern Japan. One thousand and seventy-one subjects (362 males and 709 females) who provided both self-administered validated food frequency questionnaires and blood samples were the basis for the study, and all of them were serologically positive for H. pylori immunoglobulin G (IgG) antibody. Among them, 663 (223 males and 440 females) were diagnosed as having atrophic gastritis on the basis of serum pepsinogen levels. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated based on tertile categories of subjects without atrophic gastritis, using logistic regression analysis. Among females, high consumptions of rice (OR = 1.6, 95% CI: 1.1-2.3), cod roe (OR = 1.5, 95% CI: 1.0-2.2) and cuttlefish (OR = 1.5, 95% CI: 1.0-2.3) were associated with a moderately increased risk of atrophic gastritis after adjustment for age (P for trend = 0.02 for these items). Among males, high consumptions of rice and miso soup showed a tendency toward an increased risk (P for trend = 0.12 and 0.13, respectively). Vegetables and fruits showed no association among either males or females. From these results, it is suggested that the dietary habits of consumers of traditional Japanese foods may play a role in the development of atrophic gastritis after H. pylori infection.

We conducted a population-based, double-blind, randomized controlled trial to examine the effect of vitamin C supplementation on serum pepsinogen (PG) level, Helicobacter pylori (H. pylori ) infection, and cytotoxin-associated gene A (Cag A) status. Subjects aged 40 to 69 years living in one village in Akita prefecture, a high-risk area for gastric cancer in Japan, were recruited through annual health check-up programs. Among 635 subjects diagnosed as having chronic gastritis on the basis of serum PG levels, after excluding ineligible cases, 439 subjects were assigned to one of four groups using a 2 x 2 factorial design (0 or 15 mg/day beta-carotene and 50 or 500 mg/day vitamin C). However, based on the results from two beta-carotene trials in the United States, we discontinued beta-carotene (vitamin C supplementation was continued). Finally, 120 subjects in the low-dose group (vitamin C 50 mg), and 124 subjects in the high-dose group (vitamin C 500 mg) completed the 5-year supplementation. The difference in the change of PGI/II ratio between baseline and after 5-year follow up was statistically significant between the intervention groups among those who completed the supplementation: - 0.25 for the low-dose group and - 0.13 for the high-dose group (P = 0.046). To conclude, vitamin C supplementation may protect against progression of gastric mucosal atrophy.