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Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow‐up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70–0.96) and 0.78 (95% CI = 0.65–0.94). The protective association of parity and lung cancer incidence was greater among ever‐smokers (HR = 0.66, 95% CI = 0.49–0.87) than in never‐smokers (HR = 0.90, 95% CI = 0.74–1.09) (P‐interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21–25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non‐small cell lung cancer (HR = 1.31, 95% CI = 1.02–1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time. [ABSTRACT FROM AUTHOR]

Background Although studies have found an association between chronic kidney disease (CKD) and cancer incidence, the results are inconsistent. Methods This study included participants in the Japan Public Health Center-based Prospective Study who had data on serum creatinine measurements. We assessed the association between estimated glomerular filtration rate (eGFR) and the risk of total and site-specific cancer incidence using a systematic survey in Japan. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for participant demographics and lifestyle factors. Results A total of 21 978 participants who met the inclusion criteria were followed up for a mean period of 12.9 years, during which a total of 2997 incident cancer cases were reported. In the multivariable adjusted models, an eGFR of <45 mL/min/1.73 m2 was not significantly associated with total cancer incidence (adjusted HR 1.22, 95% CI 0.94–1.60), compared with an eGFR of 60–89 mL/min/1.73 m2 (reference). The HR among those with eGFRs of ≥90 mL/min/1.73 m2 was 1.10 (95% CI 1.00–1.22). Conclusions In this large prospective study, a low eGFR was not significantly associated with an increased risk of total cancer incidence in patients with CKD, which may be partly due to an underpowered sample size. This finding may be due to the many shared risk factors between CKD and cancer. [ABSTRACT FROM AUTHOR]

The influence of sugar consumption on the risk of colorectal cancer (CRC) remains controversial. Prospective cohort studies focusing on total and specific types of sugar intake among the Asian population who have different patterns of sugar intake sources than American and European populations are scarce. We intended to examine the association of sugar intake with CRC risk among middle‐aged adults in a Japanese large‐scale population‐based cohort study. The participants (42,405 men and 48,600 women) who were 45–74 years old and answered the questionnaire in 1995–1999 in the Japan Public Health Center‐based Prospective Study were followed up until December 2013. Total sugars, total fructose, and specific types of sugar intake were estimated using a validated 147‐item food frequency questionnaire and divided into quintiles (Q1–Q5). We used Cox proportional hazard regression models adjusted for potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During the follow‐up, 2118 CRC cases (1226 men and 892 women) were identified. We did not observe any clear association between all types of sugar intake and an increased risk of CRC. Analyses by tumor sites yielded a positive association of total sugar consumption with rectal cancer in women (1.75 [1.07–2.87] for Q1 vs. Q5; plinear trend = 0.03), but no statistically significant trend was detected among men. Sugar intake was not associated with CRC risk in middle‐aged Japanese adults. However, for rectal cancer, the probability of an increased risk among women with a higher total sugar intake cannot be excluded. [ABSTRACT FROM AUTHOR]

The tumor suppressor protein, p53, is a critical molecule involved in cancer development. However, the association between p53 Arg72Pro polymorphism and cancer risk remains unclear, possibly due to the pro‐tumor potential of p53 under metabolic stress. Here, we hypothesized that the p53 Arg72Pro polymorphism plays different roles during tumorigenesis by adiposity status. We measured baseline body mass index (BMI) and p53 Arg72Pro polymorphism for two case‐cohorts, which included 4264 cancers with up to 20 years of follow‐up. Multivariable‐adjusted hazard ratios (HRs) and confidence intervals (CIs) were estimated using weighted Cox proportional‐hazards method. Without consideration of adiposity status, p53 Arg72Pro polymorphism was not associated with cancer risk. However, proline (Pro) homozygous genotype conferred an increased cancer risk for individuals with a BMI <25 kg/m2 (HR [95% CI]: 1.12 [1.00–1.26] for total cancer and 1.19 [1.02–1.38] for obesity‐related cancer), but not for those with a BMI ≥ 25 kg/m2. The heterogeneous effect of p53 Arg72Pro polymorphism on cancer risk according to adiposity status was indicated (pheterogeneity: 0.07 for total cancer and 0.03 for obesity‐related cancer). Furthermore, the association between overweight and cancer risk was only observed in arginine (Arg) carriers, but not in Pro homozygous carriers (pheterogeneity: 0.07 for total cancer and 0.02 for obesity‐related cancer). Pro homozygous carriers were more likely to be predisposed to cancer than Arg carriers with normal‐weight conditions. In addition, overweight was related to a higher cancer risk in Arg carriers than Pro homozygous carriers. Our findings may suggest the adiposity‐dependent dual effects of p53 Arg72Pro polymorphism during tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) plays a major role as a "danger signal" on stressed cells to promote removal of the latter by NKG2D-expressing cytotoxic lymphocytes. NKG2DL expression has been found in peripheral immune cells as well, such as in macrophages; however, the effect of this expression is yet to be determined. Methods: We determined instrumental variables (IVs; R2 <0.01 in linkage disequilibrium), explaining the major variance in major histocompatibility complex class I chain-related protein A (MICA) and B (MICB) gene expression levels from the expression-quantitative trait locus (eQTL) of NKG2DLs based on the RNA-seq analysis of peripheral blood mononuclear cells (PBMCs) from 381 Japanese. Simultaneously, the target outcomes were filtered by PheWAS from 58 health risks, using a community-based cohort study composed of 44,739 Japanese residents. Finally, we estimated the causal effect of gene expression levels on the outcomes using the Mendelian randomization approach. Results: We determined nine and four IVs, explaining 87.6% and 33.0% of MICA and MICB gene expression levels, respectively. In the association test, we identified 10 or 13 significant outcomes associated with the MICA or MICB eQTLs, respectively, as well as the causal effect of MICA expression on Graves' disease (GD) (p = 4.2 × 10−3; odds ratio per 1 S.D. difference in the expression: 0.983 [confidence interval: 0.971–0.995]), using the weighted median estimator, without significant pleiotropy (p > 0.05), and the results were consistent across the sensitivity analyses. Conclusions: Our study provide novel evidence associating NKG2DL expression with GD, an autoimmune thyroiditis; direction of the effect indicated the immunoregulatory role of MICA expression in PBMCs, suggesting the importance of further functional assays in inflammatory diseases. [ABSTRACT FROM AUTHOR]

Escherichia coli containing polyketide synthase in the gut microbiota (pks+E coli) produce a polyketide‐peptide genotoxin, colibactin, and are suspected to play a role in the development of colorectal neoplasia. To clarify the role of pks+E coli in the early stage of tumorigenesis, we investigated whether the pks status of E coli was associated with the prevalence of colorectal neoplasia. This cross‐sectional analysis of data from a prospective cohort in Izu Oshima, Japan included asymptomatic residents aged 40‐79 years who underwent screening colonoscopy and provided a stool sample. We identified 543 participants with colorectal neoplasia (22 colorectal cancer and 521 adenoma) as cases and 425 participants with normal colon as controls. The pks status of E coli was assayed using stool DNA and specific primers that detected pks+E coli. The proportion of pks+E coli was 32.6% among cases and 30.8% among controls. Compared with those with pks−E coli, the odds ratio (OR) (95% confidence interval) for participants with pks+E coli was 1.04 (0.77‐1.41) after adjusting for potential confounders. No statistically significant associations were observed regardless of tumor site or number of colorectal adenoma lesions. However, stratified analyses revealed increased ORs among participants who consumed cereals over the median intake or vegetables under the median intake. Overall, we found no statistically significant association between pks+E coli and the prevalence of colorectal adenoma lesions among this Japanese cohort. However, positive associations were suggested under certain intake levels of cereals or vegetables. [ABSTRACT FROM AUTHOR]

Evidence supporting the association of glycemic index (GI) and glycemic load (GL) with the risk of endometrial cancer is controversial and reports from Asia were limited. Therefore, we aimed to investigate the association in Japanese women. We evaluated 52 460 women in the Japan Public Health Center‐based Prospective Study aged 45‐74 years who responded to the 5‐year follow‐up survey. GI and GL were calculated from a validated food frequency questionnaire, and the participants were divided into three groups by GI and GL. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with the Cox proportional hazard model adjusted for potential confounding factors. As a result, within 15.5 years of follow‐up, 166 new cases of endometrial cancer were identified. Compared with the lowest GI and GL tertile groups, the HR of the risk of endometrial cancer in the highest GI tertile group was 0.80 (95% CI, 0.53‐1.20; Ptrend =.33), and that of the highest GL tertile group was 0.79 (95% CI, 0.52‐1.19; Ptrend =.82). The results were unchanged after stratification by body mass index, coffee consumption, and history of diabetes. In conclusion, we did not find any significant association between GI and GL with the risk of endometrial cancer. Further research is required to clarify the association. [ABSTRACT FROM AUTHOR]

Evidence of the association between dietary fiber intake and gastric cancer (GC) risk from prospective studies is limited. We examined the association between dietary fiber intake and GC risk in a large prospective study. A total of 91 946 eligible Japanese aged 45 to 74 years (42 773 men and 49 173 women) participated in a population‐based cohort study (Japan Public Health Center‐based prospective study). From a validated food frequency questionnaire with 138 food items, total and food source‐specific dietary fiber intake was calculated as exposure. The hazard ratio (HR) and the 95% confidence interval (CI) of GC incidence according to quintile of dietary fiber intake were examined after adjusting for confounding factors. In total, 2228 GC cases (1559 men and 669 women) were observed during the 15.0 years follow‐up. Total dietary fiber intake was not associated with GC risk; however, a marginally increased risk trend because of high HR in the highest quintile of total fiber intake was found in women (HR [95% CI] in Q5 vs Q1: 0.95 [0.79‐1.14], P for trend.30 in men, HR [95% CI] 1.25 [0.98‐1.61], P for trend.05 in women). Stratification by tumor location did not change the results. A marginal but not significant inverse trend was observed regarding cereal fiber intake and GC risk in men. Total dietary fiber intake was not associated with GC risk. Further studies are warranted to confirm this association. What's new? Since dietary fiber is abundantly contained in whole grains, fruits, and vegetables, it is expected to have beneficial effects on health. But so far, only the association with decreased colorectal cancer risk has been fully established. In a 15‐year prospective study with more than 2000 gastric cancer cases from 91 946 Japanese subjects, total dietary fiber intake was not associated with gastric cancer risk. However, a marginally increased association between total fiber intake and gastric cancer incidence in women, and a non‐significant inverse trend with cereal fiber intake in men, was observed. Stratification by tumor location did not change the results. [ABSTRACT FROM AUTHOR]