No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3).

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

[Assessment of renal function with intravoxel incoherent motion and diffusion tensor imaging in type 2 diabetic patients].

Objective: To evaluate the application value of intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) in detecting early-stage diabetic nephropathy and to assess the damage of ralated renal function. Methods: A total of 52 patients with type 2 diabetes diagnosed in Zhongda Hospital were collected from April 2016 to May 2017 and were assigned to DM group (diabetes without nephropathy, n=32) and DN group (diabetes with nephropathy, n=20) according to detection of microalbuminuria, a cohort of healthy recipients were included as control group (n=27) in the meantime. All of the subjects underwent IVIM and DTI examination. The cortical and medullary parameters[IVIM: perfusion fraction f, tissue diffusivity D, pseudodiffuvisity D(*;) DTI: fractional anisotropy FA, apparent diffusion coefficient ADC, principal diffusivities (λ1, λ2, λ3)]were obtained respectively and were compared among groups. The relationship between MRI related parameters and estimated glomerular filtration rate (eGFR) were statistically investigated; and diagnostic performance of IVIM and DTI in discriminating DM and DN group was evaluated by receiver operating characteristic analysis. Results: The cortical and medullary f, D values in DN group were lower than those in DM group and control group (F=17.32, 15.69, 6.71, 10.94, all P<0.05). D values of all subjects showed positive correlations with eGFR (cortex r=0.518, medulla r=0.538, both P<0.05). The diagnostic efficiency of cortical f values to discriminate diabetes and diabetic nephropathy was 0.817, the cut-off value was 0.205. The medullary FA value in DM group was lower than that in control group ((0.371±0.051 vs 0.423±0.043, t=4.188, P<0.05); and the medullary FA value in DN group (0.315±0.062) was lower than that in control and DM group (F=25.08, P<0.05). The medullary λ3 values in DM group and DN group were all significantly higher than that in control group (F=7.86, P<0.05). The diagnostic efficiency of medullary FA values to discriminate diabetes and diabetic nephropathy was 0.763, the cut-off value was 0.344. Conclusion: IVIM and DTI can reflect the abnormal perfusion and diffusion during early-stage diabetic nephropathy and have the potential value to assess the damage of ralated renal function.

[Application of long term video electroencephalogram and resting-state functional magnetic resonance imaging in detection of cognition in patients with benign epilepsy of childhood with centrotemporal spikes].

Objective: To study the relationship between the changes of brain network and cognition in patients with benign epilepsy of childhood with centrotemporal spikes (BECTS) by using long term video electroencephalogram (VEEG) and resting-state functional magnetic resonance imaging (RS-fMRI) technology. Methods: Eleven patients with right-handed were recruited (from April 2015 to September 2016) from epilepsy specialist outpatients and functional department of neurosurgery of Tianjin Medical University General Hospital. They all underwent the long term VEEG monitoring (one sleep cycle was included at least). According to the spike-wave index (SWI) during slow ware sleep, they were divided into two groups: SWI<50% (5 cases) and SWI≥50% (6 cases). All the patients were assessed with cognitional test including language, execution, memory and attention. They also underwent the head MRI, RS-fMRI examinations. Then the results were comparatively analysed. Results: (1)There were no statisticaly significance in sex, age, age of onset, disease course, total number of seizures, years of education (P>0.05). The Full Intelligence Quotient (FIQ) (87±18), Verbal Intelligence Quotient (VIQ) (88±15) and Performance Intelligence Quotient (PIQ) (89±20) of SWI≥50% group were lower than SWI<50% group(118±8, 114±11, 119±5) and the differences were statistically significant(P<0.05). (2)There was a negative correlation between the FIQ (P=0.002), VIQ (P=0.006), PIQ (P=0.001) and SWI. The FIQ, VIQ and PIQ had no correlation with the sex, age, age of onset, disease course, total number of seizures, years of education (P>0.05). (3)Compared with SWI<50% group, SWI≥50% group showed increased regional homogeneity (ReHo) in the bilateral precentral gyrus, premotor area and the subcortical structure, the right temporal lobe and the bilateral insular lobe(P<0.05); while they showed decreased ReHo in the posterior cingulate gyrus, right posterior inferior temporal lobe and right occipital lobe(P<0.05). Conclusion: The change of the brain network which is caused by the paradoxical and constant discharge during slow ware sleep in patients with BECTS may affect the development of cognition.

[The stimulation of human pulmonary artery endothelial cells by cigarette smoke extract contributed to cell senescence and induced human pulmonary artery smooth cell migration].

Objective: To observe the senescent effect of human pulmonary arterial endothelial cells (HPAEC) stimulated by cigarette smoke extract (CSE) and the effect of secretion of senescent cells on human pulmonary arterial smooth muscles cell (HPASMC) proliferation and migration. Methods: HPAEC was treated with different concentrations of CSE in vitro and cell proliferation was determined by CCK8, senescence cells analyzed by detecting the ß-gal activity, and the senescent proteins of cells measured by Western blot. The concentration of senescence-associated secretory phenotype (SASP) was detected by ELISA and the expression of MCP-1 and TGF-ß1 was measured by Real-time PCR. The number of the proliferated cells was measured by Transwell assay and immunoflurescence. Results: The HPAEC was aging with the stimulation concentration of CSE increasing and the stimulation time prolonging (P<0.05). Western blot indicated that the senescent associated protein p53 or p21 increased markedly after 48 h and 72 h CSE-exposure (n=3, P<0.05). The SA-ß-Gal staining showed that the number of senescent cells increased as the exposure time prolonged. Compared with the control group, cell viability of 48 h group(1.8±0.1) and 72 h group (1.8±0.1) decreased significantly. The flow cytometry showed a significant difference between the CSE group(14.1±1.2) and the control group(28.5±1.8) in S phase(P<0.01), indicating cell cycle arrest. The SASP was increasing as the CSE-exposure prolonged. Compared with the control group(177±39), the 48 h group(460±43) and the 72 h group(609±64) showed a marked increase in MCP-1(P<0.05). For TGF-ß1, it had a same tendency and a significant difference between the control group(121±18) and the 48 h group(413±32) or 72 h group(606±67, both P<0.05). In the meantime, the bFGF increased after 48 h stimulation(291±13, P<0.05). Besides MCP-1, TGF-ß1 showed a significant difference between the control group and the 72 h CSE-exposure group (P<0.01). Premature cells could secrete SASP which induced HPASMC proliferation. After different times of conditioned medium stimulation, HPASMC proliferated especially at 72 h(P<0.05) . The immnoflorescence and Transwell assay confirmed this finding. Conclusion: CSE could induce senescence of HPAEC and SASP production which improved HPASMC proliferation and migration.

Breast cancer incidence and mortality: trends over 40 years among women in Shanghai, China.

BACKGROUND: Breast cancer incidence rates are increasing among Asian women, likely due to the changes in risk factors caused by globalization. Trends in breast cancer rates among Chinese women may differ from other Asian regions due to the implementation of a nationwide family planning program and resulting changes in women's reproductive practices. Appraisal of cancer trends can direct cancer control and public health planning, but relevant studies in China are scarce due to a lack of long-term data. We sought to evaluate secular time trends in breast cancer incidence and mortality using 40 years of cancer registry data for women in urban Shanghai. MATERIALS AND METHODS: Data on invasive breast cancer incidence and mortality were collected by the Shanghai Cancer Registry. Age-standardized rates (ASRs) for incidence and mortality were calculated using the Segi/Doll 1960 world standard population. Age, period, and birth cohort effects were evaluated using age-period-cohort (APC) Poisson regression models. Overall linear trends, interpreted as the estimated annual percentage change (EAPC), were derived from the net drift in age-drift models. RESULTS: A total of 53 885 breast cancer cases and 17 235 breast cancer-specific deaths were documented among women in urban Shanghai between 1 January 1973 and 31 December 2012. Breast cancer incidence and mortality ASRs increased by 141.2% and 26.6%, respectively. Significant age, cohort, and period effects were identified in both incidence and mortality APC models; cohort effects were pronounced. Overall, a substantial increase in breast cancer incidence (EAPC = 2.96%/year) and a moderate increase in breast cancer mortality (EAPC = 0.87%/year) was observed. A notable downward trend in mortality was identified among younger women born after 1960. CONCLUSIONS: Forty years of cancer registry data document a tremendous increase in incidence and a slight increase in mortality for breast cancer among women in Shanghai. Effective, appropriate, and affordable breast cancer prevention and control strategies are urgently needed in China.

Oral health and risk of colorectal cancer: results from three cohort studies and a meta-analysis.

BACKGROUND: While studies have shown that poor oral health status may increase the risk of cancer, evidence of a specific association with the risk of colorectal cancer (CRC) is inconclusive. We evaluated the association between oral health and CRC risk using data from three large cohorts: the Shanghai Men's Health Study (SMHS), the Shanghai Women's Health Study (SWHS), and the Southern Community Cohort Study (SCCS), and carried out a meta-analysis of results from other relevant published studies. PATIENTS AND METHODS: This study applied a nested case-control study design and included 825 cases/3298 controls from the SMHS/SWHS and 238 cases/2258 controls from the SCCS. The association between oral health status (i.e. tooth loss/tooth decay) and CRC risk was assessed using conditional logistic regression models. A meta-analysis was carried out based on results from the present study and three published studies. RESULTS: We found that tooth loss was not associated with increased risk of CRC. ORs and respective 95% CIs associated with loss of 1-5, 6-10, and >10 teeth compared with those with full teeth are 0.87 (0.69-1.10), 0.93 (0.70-1.24), and 0.85 (0.66-1.11) among SMHS/SWHS participants; and 1.13 (0.72-1.79), 0.87 (0.52-1.43), and 1.00 (0.63-1.58) for those with loss of 1-4, 5-10, and >10 teeth among SCCS participants. Data regarding tooth decay were available in the SCCS, but were not associated with CRC risk. Meta-analysis confirmed the null association between tooth loss/periodontal disease and CRC risk (OR 1.05, 95% CI 0.86-1.29). CONCLUSION: In this analysis of three cohorts and a meta-analysis, we found no evidence supporting an association between oral health and CRC risk.

[Resting-state functional magnetic resonance study of the brain's network of the temporal lobe epilepsy patients with depression].

OBJECTIVE: To study brain networks of temporal lobe epilepsy (TLE) to investigate whether TLE brain dysfunction have an impact on depression, using resting state functional magnetic resonance (RS-fMRI) detection technology. METHODS: A total of 18 patients with TLE were included in this study. According to Beck Depression Inventory (BDI) and Hamilton's Depression Scale (HAMD)-17 score, we divided them into two groups: depression group 9 cases, non-depression group 9 cases. All patients underwent 3.0T MRI , RS-fMRI and magnetic resonance spectroscopy (MRS) examinations and then the results were analyzed. RESULTS: Disease course of depression group was longer than non-depression group and the difference was statistically significant (P<0.05). RS-fMRI examination showed that depression group had more active brain areas and more extral temporal active areas than non-depression group (P<0.05). By compared with the non-depression group, we found more strong active brain areas including thalamus, and the default-mode network which involved in prefrontal cortex, precuneus, ventral anterior cingulate and hippocampus. We found the NAA and NAA/Cho+ Cr of the hippocampus which were ipsilateral to the advantage discharge side were decreased in 5/9 cases with depression in MRS and 3/5 cases had hippocampal atrophy, while the non-depression group had no obvious abnormalities. CONCLUSION: The brain default-mode network activity in TLE patients with depression is increased and there is more extral temporal activation than the non-depression group; furthermore abnormal hippocampus structure is more common in depression group, which suggests that epileptic brain dysfunction may affect the development of depression.

Relationship between HLA-DP gene polymorphisms and the risk of hepatocellular carcinoma: a meta-analysis.

The association between the HLA-DP single nucleotide polymorphisms (SNPs) rs3077 and rs9277535 and hepatocellular carcinoma (HCC) has been reported, but results have been inconclusive and controversial. Therefore, to investigate the relationship between these HLA-DP SNPs and HCC susceptibility, a meta-analysis of studies published before January 2014 was carried out using the PubMed and Google Scholar databases. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated for HLA-DP alleles, and for co-dominant, dominant, and recessive genotype models of each SNP, based on fixed- or random-effects models. A total of nine studies from six published articles were included. The association study between rs3077 and HCC susceptibility was performed in four independent comparisons that contained 1871 cases with hepatitis B virus (HBV)-related HCC and 3207 carriers with persistent HBV. Association between rs9277535 and HCC susceptibility was examined in five separate comparisons that contained 2017 cases and 3930 carriers. Our analysis indicated a significant association of rs3077 and rs9277535 with HCC susceptibility, suggesting that rs3077 might act beneficially against HCC susceptibility (A vs G: OR = 0.884, 95%CI = 0.803-0.973, P = 0.012; GA vs GG: OR = 0.842, 95%CI = 0.733-0.967, P = 0.015; AA+GA vs GG: OR = 0.848, 95%CI = 0.744-0.968, P = 0.014), and that rs9277535 might promote HCC susceptibility (AA vs GA: OR = 1.202, 95%CI = 1.011-1.428, P = 0.037). This study suggested that HLA-DP rs3077 and rs9277535 polymorphisms are associated with HCC susceptibility in the Asian population.

[Advances in the application of dynamic virtual patients in prosthodontics].

With the development and application of technologies such as facial scanning, intraoral scanning, virtual facebow and mandibular movement tracking in prosthodontics, dynamic virtual patients are gradually applied to preoperative analysis, esthetic diagnosis, treatment planning, and restorative implementation, becoming a research hotspot in recent years. This review focuses on data acquisition, construction of dynamic virtual patients and their application advantages, aiming to provide a reference for the clinical application of related digital technologies.

Anthropometric measures and epithelial ovarian cancer risk among Chinese women: results from the Shanghai Women's Health Study.

BACKGROUND: Studies of anthropometric measures and ovarian cancer risk have predominantly included women of European descent with mixed findings. METHODS: Data from the prospective Shanghai Women's Health Study (SWHS) were used to evaluate associations between anthropometric measures and risk of epithelial ovarian cancer (EOC). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression. RESULTS: A total of 152 EOC cases occurred among 70 258 women. Increasing quartiles of weight, hip circumference, and weight gain during adulthood were associated with significantly increased EOC risks. Body mass index (BMI) was also associated; overweight (25BMI<29.99) and obese women (BMI30.0) had significantly increased risks (HR: 1.49, 95% CI: 1.05, 2.13, and HR: 2.42, 95% CI: 1.37, 4.28, respectively). No significant associations were observed for height, waist circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHER). CONCLUSION: Results from this large prospective study of Chinese women support the hypothesis that general adiposity contributes to the aetiology of ovarian cancer.

Cruciferous vegetables consumption and the risk of female lung cancer: a prospective study and a meta-analysis.

BACKGROUND: Epidemiological studies evaluating the association between cruciferous vegetables (CVs) intake and female lung cancer risk have produced inconsistent results. PATIENTS AND METHODS: This study followed 74 914 Chinese women aged 40-70 years who participated in the Shanghai Women's Health Study. CV intake was assessed through a validated food-frequency questionnaire (FFQ) at baseline and reassessed during follow-up. Hazard ratios (HRs) and 95% confidence interval (CIs) were estimated by using Cox proportional hazards models. Furthermore, we carried out a meta-analysis of all observational studies until December 2011. RESULTS: After excluding the first 2 years of follow-up, 417 women developed lung cancer over a mean of 11.1 years of follow-up. An inverse association of borderline statistical significance was observed between CV consumption and female lung cancer risk, with HR for the highest compared with the lowest quartiles of 0.73 (95% CI 0.54-1.00, P trend = 0.1607). The association was strengthened in analyses restricting to never smokers, with the corresponding HR of 0.59 (95% CI 0.40-0.87, P trend = 0.0510). The finding of an inverse association between CV intake and lung cancer risk in women was supported by our meta-analysis of 10 included studies. CONCLUSIONS: Our study suggests that CV consumption may reduce the risk of lung cancer in women, particularly among never smokers.

Dietary glycemic load, glycemic index, and carbohydrates on the risk of primary liver cancer among Chinese women and men.

BACKGROUND: Dietary glycemic index (GI) and glycemic load (GL) typically have a positive relationship with obesity and diabetes, which are risk factors for liver cancer. However, studies on their association with liver cancer have yielded inconsistent results. Therefore, we assessed the association of GI, GL, and carbohydrates with liver cancer risk. PATIENTS AND METHODS: A total of 72 966 women and 60 207 men from the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health Study (SMHS) were included for analysis. Food frequency questionnaire (FFQ) data were used to calculate daily dietary GI, GL, and carbohydrate intake. These values were energy adjusted and categorized into quintiles. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated with adjustment for potential confounders. RESULTS: After a median follow-up time of 11.2 years for the SWHS and 5.3 years for the SMHS, 139 and 208 incident liver cancer cases were identified in the SWHS and SMHS, respectively. In multivariable Cox regression models, no statistically significant trends by quintile of GI, GL, or carbohydrate intake were observed. Stratification by chronic liver disease/hepatitis, diabetes, or body mass index (BMI) did not alter the findings. CONCLUSIONS: There is little evidence that dietary GI, GL, or carbohydrates affect the incidence of liver cancer in this Asian population.

Prospective evaluation of type 2 diabetes mellitus on the risk of primary liver cancer in Chinese men and women.

BACKGROUND: No prospective study has investigated the relationship between type 2 diabetes mellitus (T2DM) and the risk of primary liver cancer (PLC) in mainland China, and little is known about the effect of diabetes duration on PLC risk. DESIGN: Data from two population-based cohorts (the Shanghai Men's Health Study, SMHS, 2002-2006 and the Shanghai Women's Health Study, SWHS, 1996-2000) were thus used to assess the associations among T2DM, diabetes duration and PLC risk in Chinese population. RESULTS: During follow-up through 2009, 344 incident PLC cases were identified among 60 183 men and 73 105 women. T2DM is significantly associated with the increased risk of PLC in both men [hazard ratio (HR) = 1.63, 95% confidence interval (CI) 1.06-2.51] and women (HR = 1.64, 95% CI 1.03-2.61). The highest risk of incident liver cancer was observed in the first 5 years after diabetes diagnosis, and decreased substantially with the prolonged diabetes duration (P(trend) < 0.001). No synergistic interaction in the development of PLC was found between diabetes and other known risk factors. CONCLUSIONS: T2DM is associated with the increased risk of subsequent liver cancer within 5 years after diagnosis in Chinese population, suggesting that hyperinsulinaemia rather than hyperglycaemia is more likely to be a primary mediator for this association.

Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.

Body weight, fat distribution and colorectal cancer risk: a report from cohort studies of 134255 Chinese men and women.

OBJECTIVE: The objective was to evaluate the association of body size and fat distribution with the risk of colorectal cancer (CRC) in Chinese men and women. DESIGN: This was a population-based, prospective cohort study. SUBJECTS: The analysis included 134,255 Chinese adults enrolled in the Shanghai Women's Health Study and the Shanghai Men's Health Study, with an average follow-up of 11.0 and 5.5 years, respectively. MEASUREMENTS: Waist circumference (WC), body mass index (BMI) and waist-to-hip ratio (WHR) were measured by trained interviewers at baseline. Multivariable Cox models were used to calculate adjusted hazard ratios (HRs) for incident CRC. RESULTS: A total of 935 incident CRC cases were identified. Both measures of general adiposity (measured by BMI) and central adiposity (measured by WHR and WC) were significantly associated with an increased risk of colon cancer in men but not in women. Multivariable-adjusted HRs for colon cancer in men in the highest compared with the lowest quintiles were 2.15 (95% confidence interval (CI): 1.35-3.43; P for trend=0.0006) for BMI, 1.97 (95% CI: 1.19-3.24; P for trend=0.0004) for WHR and 2.00 (95% CI: 1.21-3.29; P for trend=0.0002) for WC. The BMI-associated risk was attenuated in analyses stratified by WHR, whereas the WHR-associated risk remained significant in the high BMI stratum (HR for comparison of extreme tertiles of WHR: 3.38, 95% CI: 1.47-7.75; P for trend =0.0002). None of these anthropometric measures were significantly associated with rectal cancer. CONCLUSION: Obesity, particularly central obesity, was associated with an increased risk of colon cancer in men.

Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women.

STUDY QUESTION: Do genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry? SUMMARY ANSWER: Many genetic variants influencing age at menarche in European populations appear to impact Chinese populations in a similar manner. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Prior genome-wide association studies have uncovered 42 SNPs associated with age at menarche in European populations. This study is the first to demonstrate that many of the genetic determinants of age at menarche are shared between European and Chinese women. PARTICIPANTS AND SETTING: We evaluated 37 of 42 SNPs identified as associated with age at menarche from a recent, large meta-analysis, consisting primarily of women of European ancestry, in a population of 6929 Chinese women from Shanghai, China. We also constructed weighted genetic risk scores (GRSs) combining the number of effect variants for all 37 SNPs, or only the SNPs associated with age at menarche among our study population, to evaluate their joint influence on age at menarche. MAIN RESULTS: For 32 of the 37 evaluated variants, the direction of the allele associations were the same between women of European ancestry and women of Chinese ancestry (P = 3.71 × 10(-6), binomial sign test); 9 of these were statistically significant. Subjects in the highest quintile of GRSs began menarche ∼5 months later than those in the lowest quintile. BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS: Age at menarche was obtained by self-report, which can be subject to recall errors. The current analysis was restricted to loci which met or approached GWAS significance thresholds and did not evaluate loci which may act predominantly or exclusively in the Chinese population. The smaller sample size for our meta-analysis compared with meta-analyses conducted in European populations reduced the power to detect significant results. STUDY FUNDING/COMPETING INTERESTS: This study was supported, in part, by grants from US National Institutes of Health (grants R01CA124558, R01CA090899, R01CA070867; R01CA064277 and R01CA092585 and UL1 RR024975), Ingram professorship funds and Allen Foundation funds. There are no competing interests to declare.

Blood leukocyte Alu and LINE-1 methylation and gastric cancer risk in the Shanghai Women's Health Study.

BACKGROUND: Recent data suggest a link between blood leukocyte DNA methylation, and cancer risk. However, reports on DNA methylation from a prospective study are unavailable for gastric cancer. METHODS: We explored the association between methylation in pre-diagnostic blood leukocyte DNA and gastric cancer risk in a case-control study nested in the prospective Shanghai Women's Health Study cohort. Incident gastric cancer cases (n=192) and matched controls (n=384) were included in the study. Methylation of Alu and long interspersed nucleotide elements (LINE)-1 were evaluated using bisulphite pyrosequencing. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated from logistic regression adjusting for potential confounders. RESULTS: Alu methylation was inversely associated with gastric cancer risk, mainly among cases diagnosed one or more years after blood collection. After excluding cases diagnosed during the first year of follow-up, the ORs for the third, second, and first quartiles of Alu methylation compared with the highest quartile were 2.43 (1.43-4.13), 1.47(0.85-2.57), and 2.22 (1.28-3.84), respectively. This association appeared to be modified by dietary intake, particularly isoflavone. In contrast, LINE-1 methylation levels were not associated with gastric cancer risk. CONCLUSION: Evidence from this prospective study is consistent with the hypothesis that DNA hypomethylation in blood leukocytes may be related to cancer risk, including risk of gastric cancer.

Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium.

BACKGROUND: The evidence for a role of tobacco smoking, alcohol drinking, and body mass index (BMI) in the etiology of small intestine cancer is based mainly on case-control studies from Europe and United States. SUBJECTS AND METHODS: We harmonized the data across 12 cohort studies from mainland China, Japan, Korea, Singapore, and Taiwan, comprising over 500,000 subjects followed for an average of 10.6 years. We calculated hazard ratios (HRs) for BMI and (only among men) tobacco smoking and alcohol drinking. RESULTS: A total of 134 incident cases were observed (49 adenocarcinoma, 11 carcinoid, 46 other histologic types, and 28 of unknown histology). There was a statistically non-significant trend toward increased HR in subjects with high BMI [HR for BMI>27.5 kg/m2, compared with 22.6-25.0, 1.50; 95% confidence interval (CI) 0.76-2.96]. No association was suggested for tobacco smoking; men drinking>400 g of ethanol per week had an HR of 1.57 (95% CI 0.66-3.70), compared with abstainers. CONCLUSIONS: Our study supports the hypothesis that elevated BMI may be a risk factor for small intestine cancer. An etiologic role of alcohol drinking was suggested. Our results reinforce the existing evidence that the epidemiology of small intestine cancer resembles that of colorectal cancer.

Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS: Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.