Risk SNP in a transcript of RP11-638I2.4 increases lncRNA-YY1 interaction and pancreatic cancer susceptibility.

Tens of thousands of long non-coding RNAs (lncRNAs) have been identified through RNA-seq analysis, but the biological and pathological significance remains unclear. By integrating the genome-wide lncRNA data with a cross-ancestry meta-analysis of PDAC GWASs, we depicted a comprehensive atlas of pancreatic ductal adenocarcinoma (PDAC)-associated lncRNAs, containing 1,204 lncRNA (445 novel lncRNAs and 759 GENCODE annotated lncRNAs) and 4,368 variants. Furthermore, we found that PDAC-associated lncRNAs could function by altering chromatin activity, transcription factors, and RNA-binding proteins binding affinity. Importantly, genetic variants linked to PDAC are preferentially found at PDAC-associated lncRNA regions, supporting the biological and clinical relevance of PDAC-associated lncRNAs. Finally, we prioritized a novel transcript (MICT00000110172.1) of RP11-638I2.4 as a potential tumor promoter. MICT00000110172.1 is able to reinforce the interaction with YY1, which could reverse the effect of YY1 on pancreatic cancer cell cycle arrest to promote the pancreatic cancer growth. G > A change at rs2757535 in the second exon of MICT00000110172.1 induces a spatial structural change and creates a target region for YY1 binding, which enforces the effect of MICT00000110172.1 in an allele-specific manner, and thus confers susceptibility to tumorigenesis. In summary, our results extend the repertoire of PDAC-associated lncRNAs that could act as a starting point for future functional explorations, and the identification of lncRNA-based target therapy.

Green tea consumption is associated with reduced incident CHD and improved CHD-related biomarkers in the Dongfeng-Tongji cohort.

Prospective studies on the association of green tea with risk of coronary heart disease (CHD) incidence were scarce. This study examined whether green tea can reduce CHD incidence and have a beneficial effect on CHD-related risk markers in middle-aged and older Chinese population. We included 19,471 participants who were free of CHD, stroke or cancer at baseline from September 2008 to June 2010, and were followed until October 2013. Cox proportional hazard models were used to examine the hazard ratios (HR) of CHD incidence in relation to green tea consumption. Linear regression models were used to evaluate the effect of green tea on 5-year changes of CHD-related biomarkers. Compared with non-green tea consumers, the multivariable-adjusted HR for CHD was 0.89 (95% CI, 0.81-0.98) in green tea consumers. Particularly, the reduced risk of CHD incidence with green tea consumption was more evident among participants who were male, more than 60 years old, overweight, or with diabetes mellitus. In addition, green tea consumption improved multiple CHD-related risk markers including total cholesterol, HDL-cholesterol, triglycerides, mean platelet volume, and uric acid. In conclusion, green tea consumption was associated with a reduced risk of CHD incidence in the middle-aged and older Chinese populations, and the association might be partly due to altered CHD-related biomarkers.

Allium vegetables and garlic supplements do not reduce risk of colorectal cancer, based on meta-analysis of prospective studies.

BACKGROUND & AIMS: Laboratory studies have provided evidence that allium vegetables and garlic supplements might protect against colorectal cancer (CRC), but epidemiologic studies have produced inconsistent findings. METHODS: We conducted a meta-analysis of prospective studies evaluating the associations between allium vegetables, garlic supplements, and CRC risk. We pooled effect measures using fixed- or random-effect models, assessing the highest vs the lowest intakes. We used a dose-response regression model to evaluate the relationship between allium vegetable intake and CRC risk. RESULTS: Our analysis included 8 studies with 20 reports of the effects of allium vegetables (5458 patients with CRC including 7,125,067 person-years) and 5 studies with 11 reports of the effects of garlic supplements (2685 patients with CRC including 2,304,439 person-years). We found no association between higher intake of allium vegetables and CRC risk (relative risk [RR], 1.06; 95% confidence interval [CI], 0.96-1.17; P = .26). Intake of allium vegetables did not correspond to CRC risk (P for nonlinear = .24, P for linear = .20). In subgroup analysis, a higher consumption of allium vegetables was associated marginally with increased risk of colon cancer among women (RR, 1.23; 95% CI, 1.01-1.50; P = .05). Use of garlic supplements was associated significantly with an increased risk of CRC (RR, 1.18; 95% CI, 1.02-1.36; P = .03). CONCLUSIONS: In a meta-analysis, we found no evidence that higher intake of allium vegetables reduced the risk for CRC. We observed that garlic supplements increased the risk for CRC, but this finding requires external validation.

Different physical activity subtypes and risk of metabolic syndrome in middle-aged and older Chinese people.

BACKGROUND: The prevalence of metabolic syndrome (MetS) is growing rapidly in China. Tai chi and dancing are common types of exercise among middle-aged and elderly Chinese. It remains unclear whether these activities are associated with a lower risk of MetS. METHODOLOGY/PRINCIPAL FINDINGS: A total of 15,514 individuals (6,952 men, 8,562 women) aged 50 to 70 years from the Dongfeng-Tongji Cohort in Shiyan, China participated in a cross-sectional study. Physical activity and other lifestyle factors were assessed with semi-structured questionnaires during face-to-face interviews. MetS was defined by the current National Cholesterol Education Program/Adult treatment Panel III criteria for Asian Americans. The prevalence of MetS was 33.2% in the study population. In the multivariable-adjusted logistic regression analyses, total physical activity levels were monotonically associated with a lower odds of MetS [OR 0.75 comparing extreme quintiles, 95% confidence interval (CI) 0.66-0.86, P<0.001]. Compared with non-exercisers in a specific exercise type, jogging (OR 0.82, 95% CI 0.68-1.00, P = 0.046), tai chi (OR 0.72, 95% CI 0.60-0.88, P<0.001), and dancing (OR 0.56, 95% CI 0.47-0.67, P<0.001) were associated with significantly lower odds of MetS. Furthermore, each 1-h/week increment in tai chi and dancing was associated with a 5% (95% CI 2%-9%) and a 9% (95% CI 6%, 12%) lower risk of MetS. CONCLUSIONS/SIGNIFICANCE: Jogging, tai chi and dancing are associated with a significantly lower risk of having MetS in middle-aged and older Chinese. Future intervention studies should consider the role of jogging, tai chi and dancing in preventing MetS.

ICPS: an integrative cancer profiler system.

UNLABELLED: Founded upon the database of 570 public signatures, ICPS is a web-based application to obtain biomarker profiles among 11 common cancers by integrating genomic alterations with transcription signatures on the basis of a previously developed integrative pipeline. ICPS supports both public data and user's in-house data, and performs meta-analysis at a cancer subtype level by combining heterogeneous datasets. Finally, ICPS returns the robust gene signature containing potential cancer biomarkers that may be useful to carcinogenesis study and clinical cancer diagnosis. AVAILABILITY: http://server.bioicps.org CONTACT: zhxy@mail.tsinghua.edu.cn; zxy-dcs@mail.tsinghua.edu.cn

Adenosine diphosphate ribosyl transferase and x-ray repair cross-complementing 1 polymorphisms in gastric cardia cancer.

BACKGROUND & AIMS: Adenosine diphosphate ribosyl transferase (ADPRT) and x-ray repair cross-complementing 1 (XRCC1) are major DNA base excision repair proteins acting interactively in repair processes. This study examined the effects of ADPRT Val762Ala and XRCC1 Arg399Gln polymorphisms on ADPRT-XRCC1 interaction in vitro in cells and their contributions to gastric cardia adenocarcinoma (GCA) risk. METHODS: The ADPRT-XRCC1 interaction in cells transfected with ADPRT and XRCC1 variant complementary DNA (cDNA) constructs were examined by immunoprecipitation and immunoblotting analysis. Genotypes were analyzed in 500 patients and 1000 controls, and odds ratios (ORs) were estimated by logistic regression. RESULTS: Interactions between ADPRT-762Val and XRCC1-399Arg or XRCC1-399Gln were robust, but interactions between ADPRT-762Ala and either XRCC1-399Arg or XRCC1-399Gln were very weak. A case-control analysis showed ORs of 2.17 (95% CI, 1.55-3.04) and 1.61 (95% CI, 1.06-2.44) for GCA in the ADPRT Ala/Ala or XRCC1 Gln/Gln genotype carriers, respectively, compared with noncarriers. Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased the OR of GCA in a multiplicative manner (OR for the presence of both ADPRT Ala/Ala and XRCC1 Gln/Gln genotypes, 6.43; 95% CI, 1.80-22.97). A supermultiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CIs) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or = 24 or > 24 pack-years were 1.44 (0.89-2.32), 2.00 (1.09-3.67), or 3.19 (1.59-6.42), respectively (Ptrend test = .008). CONCLUSIONS: The ADPRT and XRCC1 polymorphisms confer host susceptibility to GCA, which might result from reduced ADPRT-XRCC1 interaction and attenuated base excision repair capacity.