We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
The relationship between dietary protein consumption and the risk of type 2 diabetes (T2D) has been inconsistent. The aim of this meta-analysis was to explore the relations between dietary protein consumption and the risk of T2D. We conducted systematic retrieval of prospective studies in PubMed, Embase, and Web of Science. Summary relative risks were compiled with a fixed effects model or a random effects model, and a restricted cubic spline regression model and generalized least squares analysis were used to evaluate the diet–T2D incidence relationship. T2D risk increased with increasing consumption of total protein and animal protein, red meat, processed meat, milk, and eggs, respectively, while plant protein and yogurt had an inverse relationship. A non-linear association with the risk for T2D was found for the consumption of plant protein, processed meat, milk, yogurt, and soy. This meta-analysis suggests that substitution of plant protein and yogurt for animal protein, especially red meat and processed meat, can reduce the risk for T2D.
Purpose
The aims of this study were to evaluate the effect of age at menarche (AM) on type 2 diabetes mellitus (T2DM) and to assess whether the fasting plasma glucose (FPG) and homeostasis model assessment (HOMA) index responses to AM and menopause status interact in Chinese rural adults.
Methods
A cross-sectional, population-based study including 23 138 participants was performed. Logistic regression and multivariable linear regression were performed to investigate the relationship between AM and glucose status. Generalized linear model was used to calculate the interaction term of AM and menopause status on FPG and the HOMA index. Interaction plot was used to interpret the significant interaction effect.
Results
Women in the later menarche age group (≥18 years) had a 17.7% lower risk of T2DM (95% confidence interval [CI]: 0.712-0.951, P = .008), after adjusting for multiple variables. Further adjustment for body mass index (BMI) completely attenuated this association (odds ratio = 0.884, 95% CI: 0.764-1.024, P = .099). A significant interaction effect of AM and menopause status on T2DM (P = .004) was observed. The adverse effects of menopausal status on FPG and HOMA-2 of insulin resistance decreased with increasing menarche age, and the age ranges were limited to <18 and 9 to 19 years, respectively.
Conclusions
Later menarche was associated with a lower risk of T2DM, and the association appears to be mediated by BMI. More importantly, the adverse effect of menopause status on T2DM was decreased along with increasing menarche age.
Objective:
The aim of the study was to determine if early menarche is associated with an increased risk of type 2 diabetes mellitus (T2DM) in rural Chinese women and to estimate the proportion that can be attributed to adiposity.
Methods:
A total of 15,346 postmenopausal women were enrolled in this study. Logistic regression and restricted cubic spline analysis were performed to estimate the relationship between age at menarche and T2DM. Mediation analysis was used to investigate whether the association was mediated by body mass index (BMI).
Results:
After adjusting for multiple confounders, the early menarche group (≤14 y) had a higher risk of T2DM (odds ratio [OR] = 1.21; 95% CI = 1.06-1.38; P = 0.004) compared with the reference group (16-17 y), whereas the late onset group (≥19 y) had a lower risk of T2DM (OR = 0.78; 95% CI = 0.66-0.92; P = 0.003). BMI partially mediated the association between age at menarche and T2DM, and the proportion of the effect was 28%.
Conclusions:
Early menarche increases the risk of T2DM, whereas later menarche decreases the risk. The association seems to be partially mediated by BMI.
Aims/Introduction: Studies have found that a plant-based diet was associated with a lower risk of type 2 diabetes, but evidence is scarce on such associations in China. The aim of this study was to investigate whether a plant-based diet is related to a lower risk of type 2 diabetes among Chinese adults. Materials and Methods: A total of 37,985 participants were enrolled from the Henan Rural Cohort Study. An overall plant-based diet index (PDI) was created by assigning positive and reverse scores to 12 commonly consumed food groups. Multivariate logistic regression models and restricted cubic spline analysis were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI). Results: After multivariable adjustment, the risk of type 2 diabetes was inversely associated with the PDI (extreme-quartile OR = 0.88, 95% CI: 0.79-0.98; P = 0.027), the risk associated with a 1 standard deviation (SD) increase in PDI was 4% lower (95% CI, 0.93-1.00; P trend = 0.043) for type 2 diabetes. Moreover, the odds of type 2 diabetes was decreased with an increment of PDI after fitting restricted cubic splines (P trend < 0.01). Conclusions: Among Chinese populations, diets higher in plant foods and lower in animal foods were associated with a reduced risk of type 2 diabetes.
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