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Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.
Shi, J, Shiraishi, K, Choi, J, Matsuo, K, Chen, TY, Dai, J, Hung, RJ, Chen, K, Shu, XO, Kim, YT, et al
Nature communications. 2023;(1):3043
Abstract
Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.
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Isoflavone Consumption and Risk of Breast Cancer: An Updated Systematic Review with Meta-Analysis of Observational Studies.
Yang, J, Shen, H, Mi, M, Qin, Y
Nutrients. 2023;(10)
Abstract
RATIONALE Epidemiological studies that focus on the relationship between dietary isoflavone intake and the risk of breast cancer still lead to inconsistent conclusions. Herein, we conducted a meta-analysis of the latest studies to explore this issue. METHOD We performed a systematic search using Web of Science, PubMed, and Embase from inception to August 2021. The robust error meta-regression (REMR) model and generalized least squares trend (GLST) model were used to establish dose-response relationships between isoflavones and breast cancer risk. RESULTS Seven cohort studies and 17 case-control studies were included in the meta-analysis, and the summary OR for breast cancer was 0.71 (95% CI 0.72-0.81) when comparing the highest to the lowest isoflavone intake. A subgroup analysis further showed that neither menopausal status nor ER status has a significant influence on the association between isoflavone intake and breast cancer risk, while the isoflavone intake doses and study design does. When the isoflavones exposure was less than 10 mg/day, no effects on breast cancer risk were detected. The inverse association was significant in the case-control studies but not in the cohort studies. In the dose-response meta-analysis of the cohort studies, we observed an inverse association between isoflavone intake and breast cancer: a 10 mg/day increase in isoflavone intake was related to reductions of 6.8% (OR = 0.932, 95% CI 0.90-0.96) and 3.2% (OR = 0.968, 95% CI 0.94-0.99) in breast cancer risk when using REMR and GLST, respectively. In the dose-response meta-analysis of the case-control studies, the inverse association for every 10 mg/day isoflavone intake was associated with breast cancer risk reductions by 11.7%. CONCLUSION present evidence demonstrated that taking in dietary isoflavone is helpful in reducing the breast cancer risk.
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The effect of progesterone supplementation for luteal phase support in natural cycle frozen embryo transfer: a systematic review and meta-analysis based on randomized controlled trials.
Jiang, Y, Wang, L, Shen, H, Wang, B, Wu, J, Hu, K, Wang, Y, Ma, B, Zhang, X
Fertility and sterility. 2023;(4):597-605
Abstract
IMPORTANCE The necessity of progesterone supplementation for luteal phase support (LPS) in natural cycle frozen embryo transfer (NC-FET) cycles warrants further confirmation. OBJECTIVE To investigate the effect of progesterone supplementation for LPS on the reproductive outcomes of patients undergoing NC-FET cycles. DATA SOURCES The PubMed, Ovid-Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM were electronically searched. The search time frame was from inception up to September 2022. STUDY SELECTION AND SYNTHESIS Randomized controlled trials (RCTs) that used progesterone for LPS in NC-FET cycles, including true NC-FET cycles (tNC-FET) and modified NC-FET cycles (mNC-FET), were included. The counted data were analyzed using relative risk (RR) as the effect-size statistic, and each effect size was assigned its 95% confidence interval (CI). MAIN OUTCOME MEASURES The primary outcomes were the live birth rate (LBR) and the clinical pregnancy rate (CPR), and the secondary outcome was the miscarriage rate. RESULTS Four RCTs were included, which involved 1116 participants. The results of the meta-analysis showed that progesterone supplementation was associated with increased LBR (RR, 1.42; 95% CI, 1.15-1.75; I2 = 0%, moderate-quality evidence) and CPR (RR, 1.30, 95% CI, 1.07-1.57; I2 = 0%, moderate-quality evidence) in patients undergoing NC-FET cycles. Subgroup analysis showed that progesterone supplementation was associated with higher LBR and CPR in tNC-FET cycles. However, no association was found between increased LBR and CPR in mNC-FET cycles. In addition, only one RCT reported that oral dydrogesterone had similar CPR and miscarriage rate compared with vaginal progesterone in mNC-FET cycles. CONCLUSION(S): Overall, moderate-quality evidence suggested that progesterone supplementation for LPS was associated with increased LBR and CPR in NC-FET cycles. Progesterone supplementation was associated with a higher LBR and CPR in tNC-FET cycles. However, the effectiveness of progesterone supplementation in mNC-FET cycles should be further verified by larger RCTs. Low to very low-quality evidence indicated that oral dydrogesterone and vaginal progesterone have similar reproductive outcomes in mNC-FET cycles, which requires further study, especially in tNC-FET cycles. REGISTRATION NUMBER PROSPERO CRD42022355550 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=355550) was registered on September 3, 2022.
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Risk assessment for colorectal cancer via polygenic risk score and lifestyle exposure: a large-scale association study of East Asian and European populations.
Xin, J, Du, M, Gu, D, Jiang, K, Wang, M, Jin, M, Hu, Y, Ben, S, Chen, S, Shao, W, et al
Genome medicine. 2023;(1):4
Abstract
BACKGROUND The genetic architectures of colorectal cancer are distinct across different populations. To date, the majority of polygenic risk scores (PRSs) are derived from European (EUR) populations, which limits their accurate extrapolation to other populations. Here, we aimed to generate a PRS by incorporating East Asian (EAS) and EUR ancestry groups and validate its utility for colorectal cancer risk assessment among different populations. METHODS A large-scale colorectal cancer genome-wide association study (GWAS), harboring 35,145 cases and 288,934 controls from EAS and EUR populations, was used for the EAS-EUR GWAS meta-analysis and the construction of candidate EAS-EUR PRSs via different approaches. The performance of each PRS was then validated in external GWAS datasets of EAS (727 cases and 1452 controls) and EUR (1289 cases and 1284 controls) ancestries, respectively. The optimal PRS was further tested using the UK Biobank longitudinal cohort of 355,543 individuals and ultimately applied to stratify individual risk attached by healthy lifestyle. RESULTS In the meta-analysis across EAS and EUR populations, we identified 48 independent variants beyond genome-wide significance (P < 5 × 10-8) at previously reported loci. Among 26 candidate EAS-EUR PRSs, the PRS-CSx approach-derived PRS (defined as PRSCSx) that harbored genome-wide variants achieved the optimal discriminatory ability in both validation datasets, as well as better performance in the EAS population compared to the PRS derived from known variants. Using the UK Biobank cohort, we further validated a significant dose-response effect of PRSCSx on incident colorectal cancer, in which the risk was 2.11- and 3.88-fold higher in individuals with intermediate and high PRSCSx than in the low score subgroup (Ptrend = 8.15 × 10-53). Notably, the detrimental effect of being at a high genetic risk could be largely attenuated by adherence to a favorable lifestyle, with a 0.53% reduction in 5-year absolute risk. CONCLUSIONS In summary, we systemically constructed an EAS-EUR PRS to effectively stratify colorectal cancer risk, which highlighted its clinical implication among diverse ancestries. Importantly, these findings also supported that a healthy lifestyle could reduce the genetic impact on incident colorectal cancer.
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Urinary iodine is increased in papillary thyroid carcinoma but is not altered by regional population iodine intake status: a meta-analysis and implications.
Yan, AR, Zhang, X, Shen, H, Zhou, X, Li, R, Yuan, Z
Endocrine journal. 2019;(6):497-514
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Abstract
Excessive iodine intake has been associated with increased risk of thyroid cancer (TC) in many studies, but the results have not been consistent. Since it was common knowledge that urinary iodine (UI) is considered a sensitive marker of current iodine intake, we conducted a meta-analysis to clarify the association between high UI and TC. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and the Cochrane Collaboration. Between-group meta-analyses were performed to compare UI between TC patients and the healthy/euthyroid subjects in local residents and benign thyroid nodules (BTN) patients. Then, between-group meta-analyses to compare the incidence rate of iodine excess were also conducted. The 22 case-control studies included in the meta-analyses represented 15,476 participants. It is the first time to clarify that UI was increased in PTC patients, but was not altered by regional population iodine intake status. Compared with BTN patients, PTC patients exhibited both higher UIC and higher odds ratio of iodine excess only in adequate iodine intake status subgroup; UIC, not the odds ratio of iodine excess, was higher in patients with PTC than those with BTN in above requirements iodine intake subgroup. A novel insight is offered that high UI in PTC patients was less influenced by regional population iodine intake status. It is indicted that high iodine intake is not a risk factor for PTC and high urinary iodine is just a specific characteristic of the disease.
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Tai chi for treating osteopenia and primary osteoporosis: a meta-analysis and trial sequential analysis.
Zhang, Y, Chai, Y, Pan, X, Shen, H, Wei, X, Xie, Y
Clinical interventions in aging. 2019;:91-104
Abstract
PURPOSE The aim of this meta-analysis was to evaluate the efficacy of Tai chi (TC) as an adjuvant treatment for osteopenia and primary osteoporosis. METHODS We went through eight databases to identify relevant randomized controlled trials that compared TC with a control group. The primary outcome was osteoporosis-related fractures (fracture incidence). Meta-analyses and trial sequential analyses (TSA) were conducted using RevMan 5.3 and TSA 0.9. RESULTS Fifteen randomized controlled trials involving a total of 857 patients were included in the analyses. No trials reported primary outcome; however, bone mineral density (BMD) values differed significantly in subgroup 1 (TC vs no treatment; weighted mean difference [WMD] =0.05 g/cm2, 95% CI 0.03 to 0.07; P<0.00001; P for heterogeneity =0.22, I 2=22%) and subgroup 2 (TC vs conventional treatments; WMD =0.16 g/cm2, 95% CI 0.11 to 0.21; P<0.00001; P for heterogeneity =0.008, I 2=75%). In addition, two trials compared TC with conventional treatments, which found a significant difference in bone gla protein (standardized mean difference =-1.18, 95% CI -1.66 to -0.70; P<0.00001; P for heterogeneity =0.58, I 2=75%). The results of the BMD were confirmed by TSA. Also, TC may have a certain effect on the relief of osteoporotic pain (WMD = -2.61, 95% CI -3.51 to -1.71; WMD = -1.39, 95% CI -2.01 to -0.77). However, it did not promote the quality of life, level of serum calcium, serum phosphorus, and also had no effect on bone turnover markers. CONCLUSION Although there is no study monitoring fracture incidence, TC may be beneficial for patients in improving BMD values, level of bone gla protein, and relieving osteoporotic pain. However, due to the low methodological quality, current evidence for treating osteopenia and primary osteoporosis through TC is insufficient.
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Dietary fiber intake and reduced risk of ovarian cancer: a meta-analysis.
Zheng, B, Shen, H, Han, H, Han, T, Qin, Y
Nutrition journal. 2018;17(1):99
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Dietary factors, including glycaemic load, fat, phytoestrogen, fruit and vegetable intake, play an important role in the development of ovarian cancer. The aim of this meta-analysis was to examine: 1. The available evidence from epidemiological studies; 2. The differences of ovarian cancer risk reported according to study design, geographic location and types or sources of fibre; 3) A possible dose-response relationship between dietary fibre intake and risk of ovarian cancer. 13 studies, comprising 5,777 ovarian cancer cases and 142,189 participants, published between 1994 and 2015, were included in this meta-analysis. All studies measured dietary intakes using a food-frequency questionnaire. The meta-analysis showed that the women with the highest intake of total fibre had a significantly lower risk (22%) of developing ovarian cancer than those with the lowest fibre intake, and that there was a dose dependent reduction in risk, for every 10g of fibre consumed, there was a 12% reduction in risk. When looking at different types/sources of fibre, vegetable fibre showed the biggest protective effect, whilst cereal fibres showed an increased risk for ovarian cancer. Factors which influenced the risk were contraceptive use and menopausal status. The authors discuss possible mechanisms for the protective effect of fibre: 1. Decrease of circulating oestrogen through changing of bacterial composition in the gut and 2. Reduction of glycaemic load through fibre.
Abstract
BACKGROUND Epidemiological studies regarding the association between dietary fiber intake and ovarian cancer risk are still inconsistent. We aimed to review the available evidence and conduct a dose-response meta-analysis to investigate the relationship between dietary fiber intake and ovarian cancer risk. METHODS Relevant studies were identified by searching PubMed, EMBASE, and the Cochrane Library databases before August 2017. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between dietary fiber intake and risk of ovarian cancer were included. Random-effects models were used to combine the estimated effects extracted from individual study. RESULTS Thirteen studies, with a total of 5777 ovarian cancer cases and 142,189 participants, met the inclusion criteria. The pooled multivariable RRs of ovarian cancer for the highest vs. the lowest category of dietary fiber intake was 0.78 (95% CI: 0.70, 0.88) with no evidence of heterogeneity (I2 = 4.20%, P = 0.40). Our dose-response analysis also showed a significant inverse association between dietary fiber intake and ovarian cancer risk (an increment of 10 g/day; combined RR: 0.88; 95% CI: 0.82, 0.93). There was no evidence for a nonlinear association (P for nonlinearity = 0.83). CONCLUSIONS This meta-analysis suggests a significant inverse dose-response association between dietary fiber intake and ovarian cancer risk. Further studies with prospective design that take account of more potential confounders are warranted to confirm this association.
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Association between vitamin D receptor BsmI polymorphism and bone mineral density in pediatric patients: A meta-analysis and systematic review of observational studies.
Bao, L, Chen, M, Lei, Y, Zhou, Z, Shen, H, Le, F
Medicine. 2017;(17):e6718
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Abstract
BACKGROUND Vitamin D and the vitamin D receptor (VDR) are important in the metabolic processes that affect bone mineral density (BMD). However, the effect of VDR BsmI polymorphism on BMD in pediatric patients is still unclear. METHODS Eligible studies were identified from the following electronic databases: PubMed, Embase, the Cochrane Library, and the Chinese CNKI and Wanfang databases before October 1, 2016. Data were extracted from the eligible studies, and associations between VDR BsmI polymorphism and BMD in pediatric patients were estimated with weighted mean differences (WMDs) and 95% confidence intervals (CIs). Subgroup analysis of ethnicity and sensitivity analyses were used to identify sources of heterogeneity. RESULTS A significant difference was observed between VDR BsmI polymorphism and pediatric BMD levels of the lumbar spine (LS) in the corecessive model (bb vs BB + Bb: WMD = -0.23, 95% CI [-0.35, -0.11], P < 0.01). No significant relationship was found in the dominant, recessive, or codominant models for LS BMD (BB vs Bb: WMD = -0.56, 95% CI [-1.58, 0.46], P = 0.29; BB vs bb: WMD = -0.54, 95% CI [-1.49, 0.41], P = 0.27; and BB vs Bb + bb: WMD = -0.45, 95% CI [-1.71, 0.26], P = 0.22). In addition, we found no remarkable association between the BsmI polymorphism and BMD levels of the femoral neck (FN) in children (BB vs Bb: WMD = -1.08, 95% CI [-3.13, 0.96], P = 0.30; BB vs bb: WMD = 0.98, 95% CI [-0.89, 2.85], P = 0.31; BB vs Bb + bb: WMD = -0.061, 95% CI [-0.30, 0.17], P = 0.61; and bb vs BB + Bb: WMD = 0.82, 95% CI [-0.59, 2.32], P = 0.25). CONCLUSION Our meta-analysis found that the VDR BsmI genetic polymorphism was correlated with LS BMD level in pediatric patients: compared with those with the B allele, children with the bb genotype were less likely to have lower BMD levels. No significant difference was identified in the pediatric FN BMD levels.
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Metabolome-wide association study identified the association between a circulating polyunsaturated fatty acids variant rs174548 and lung cancer.
Wang, C, Qin, N, Zhu, M, Chen, M, Xie, K, Cheng, Y, Dai, J, Liu, J, Xia, Y, Ma, H, et al
Carcinogenesis. 2017;(11):1147-1154
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Quantitative trait loci (QTLs) are widely used as instruments to infer causal risk factors of diseases based on the idea of mendelian randomization. Plasma metabolites can serve as risk factors of cancer, and the heritability of many circulating metabolites was high. We conducted a metabolome-wide association study (MWAS) to systematically investigate the effects of genetic variants on metabolites and lung cancer based on published genome-wide association study (GWASs) and metabolic-QTL (mQTL) study. Then we confirmed the results by subsequent genetic and metabolic validations and inferred the causal relationship between identified metabolites and lung cancer through genetic variant(s). We firstly identified six polyunsaturated fatty acids (PUFAs) represented by rs174548-linked haplotype were significantly associated with lung cancer risk in a Chinese GWAS (2311 cases and 3077 controls). Rs174548 was further confirmed to be associated with lung cancer in 13 821 Europeans and 18 471 Asians (ORmeta = 0.87, Pmeta = 1.76 × 10-15) and the effect was much stronger in females (Pinteraction = 6.00 × 10-4). We next validated rs174548-plasma PUFA association in 253 Chinese subjects (β = -0.57, P = 1.68 × 10-3). Rs174548 was also found associated with FADS1 (the major fatty acid desaturase of identified PUFAs) expression in liver tissues. Taken together, we found that rs174548 was associated with both PUFAs and lung cancer. Because rs174548 was the only mQTL variant of PUFAs reported by previous GWASs and explained a large proportion of heritability, we proposed that plasma PUFAs could be causally associated with lung cancer based on the idea of mendelian randomization. These findings provide a diet-related risk factor and may have important implications for prevention on lung cancer.
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Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.
McKay, JD, Hung, RJ, Han, Y, Zong, X, Carreras-Torres, R, Christiani, DC, Caporaso, NE, Johansson, M, Xiao, X, Li, Y, et al
Nature genetics. 2017;(7):1126-1132
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Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.