Publications by authors named "Xiao-Ou Shu"

Background: There are scarce data on risk factors for epithelial ovarian cancer (EOC) in Asian populations. Our goal was to advance knowledge on reproductive -related risk factors for EOC in a large population of Asian women.

Methods: This study used pooled individual data from baseline questionnaires in 11 prospective cohorts (baseline years, 1958-2015) in the Asia Cohort Consortium.

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Circulating lipids play a crucial role in the development of coronary artery disease (CAD). However, it is unclear whether the genetic susceptibility to hyperlipidemia may interact with lifestyle factors in CAD risk. Using UK Biobank data from 328,606 participants, we evaluated combined effects of genetic susceptibility to hyperlipidemia and lifestyle factors with risk of CAD.

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  • * Results showed that a higher PRS was more strongly related to EGFR-positive LUAD cases (OR=8.63) than to EGFR-negative cases (OR=3.50), indicating a significant association based on mutation status.
  • * These findings imply that genetic susceptibility to LUAD differs in never-smoking East Asian women depending on whether the cancer has specific mutations, which could affect public health strategies and clinical practices.*
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Background: It has been suggested that the association between body mass index and breast cancer risk differs between Asian women and Western women. We aimed to assess the associations between body mass index and breast cancer incidence in East Asian women.

Methods: Pooled analyses were performed using individual participant data of 319,189 women from 13 cohort studies in Japan, Korea, and China.

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Background: Alcohol intake can alter gut microbiome, which may subsequently affect human health. However, limited population-based, prospective studies have investigated associations of habitual and recent alcohol intake with the gut microbiome, particularly among Black/African American individuals.

Objective: We examined the association of alcohol intake with gut microbiome in a predominantly low-income Black/African American population.

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Transcriptome-wide association studies (TWAS) have been successful in identifying disease susceptibility genes by integrating cis-variants predicted gene expression with genome-wide association studies (GWAS) data. However, trans-variants for predicting gene expression remain largely unexplored. Here, we introduce transTF-TWAS, which incorporates transcription factor (TF)-linked trans-variants to enhance model building for TF downstream target genes.

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Background: Genome-wide association studies (GWAS) have identified more than 200 breast cancer risk-associated genetic loci, yet the causal genes and biological mechanisms for most loci remain elusive. Proteins, as final gene products, are pivotal in cellular function. In this study, we conducted a proteome-wide association study (PWAS) to identify proteins in breast tissue related to breast cancer risk.

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Biliary tract cancer (BTC) is potentially influenced by metabolic dysregulation yet previous metabolomic evaluations are limited. To address this gap, we prospectively investigated associations of blood metabolites and BTC risk in the UK biobank cohort study. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between 249 plasma metabolites per standard deviation and BTC risk in 232,781 participants.

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Peanut consumption could impact cardiometabolic health through gut microbiota, a hypothesis that remains to be investigated. A randomized clinical trial in Vietnam evaluated whether peanut consumption alters gut microbiome communities. : One hundred individuals were included and randomly assigned to the peanut intervention and control groups.

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  • * Researchers found that the average age girls start their periods is about 14 years, but it has been getting younger over the past 100 years.
  • * Different countries showed different trends, with some like China having ups and downs, while others like Japan and Singapore had a steady decline in the average age.
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  • A study examined the impact of family history of lung cancer (FHLC) on lung cancer incidence and mortality among East Asian individuals, using data from 478,354 participants across 11 cohorts.
  • The findings indicated that having a family history of lung cancer increased the risk of developing lung cancer by 45%, affecting both men and women, and regardless of whether individuals were smokers or non-smokers.
  • Specific lung cancer types like adenocarcinoma and squamous cell carcinoma showed even higher associated risks, but there was no significant difference in risk based on sex, smoking status, or ethnicity.
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  • The American Cancer Society suggests that doctors should talk to women about endometrial cancer risks when they reach menopause, but more younger women under 50 are being diagnosed.
  • A study looked at nearly 14,000 women with endometrial cancer and found that factors like body weight and diabetes increase the risk for both younger and older women.
  • Educating women about these risk factors could help reduce the number of cases, as many endometrial cancer cases in both age groups are linked to these factors.
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The carcinogenicity of benzene was reevaluated by the International Agency for Research on Cancer in 2017, with the Working Group reaffirming positive yet inconclusive associations with non-Hodgkin lymphoma (NHL). To extend our previous observation of a significant exposure-response for cumulative occupational benzene exposure and NHL risk among Chinese women in a population-based cohort in Shanghai, we extended follow-up of this cohort and pooled the data with a similarly designed population-based cohort of men in Shanghai. Cumulative exposure estimates were derived for 134,449 participants in the pooled analysis by combining ordinal job-exposure matrix intensity ratings with quantitative benzene measurements from an inspection database of Shanghai factories.

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  • The study examines the relationship between body mass index (BMI) and the risks of developing colorectal cancer (CRC) and dying from it in the Asian population, highlighting rising obesity rates and CRC incidence.
  • The research pooled data from 17 cohort studies spanning from 1984 to 2002, with a median follow-up of 15.2 years and included nearly 620,000 participants for CRC incidence and over 650,000 for CRC-related mortality.
  • Results indicate that higher BMI significantly increases the risk of incident CRC, with greater risks seen for those classified as obese, especially for colon cancer compared to rectal cancer, and a similar pattern was noted for CRC-related deaths.
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Background: We applied the novel Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations to evaluate cardiovascular-kidney-metabolic (CKM) health and estimated CVD risk, including heart failure (HF), after bariatric surgery.

Methods: Among 7804 patients (20-79 years) undergoing bariatric surgery at Vanderbilt University Medical Center during 1999-2022, CVD risk factors at pre-surgery, 1-year, and 2-year post-surgery were extracted from electronic health records. The 10- and 30-year risks of total CVD, atherosclerotic CVD (ASCVD), coronary heart disease (CHD), stroke, and HF were estimated for patients without a history of CVD or its subtypes at each time point, using the social deprivation index-enhanced PREVENT equations.

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Background: Benzene exposure has been associated with increased risk of leukemia and other cancers; however, epidemiologic evidence is inconsistent for the latter, and confounding from smoking and alcohol was rarely adjusted.

Methods: We investigated associations between occupational benzene exposure and risk of leukemia, lymphoma, myeloma, and lung, stomach, liver, and kidney cancers in a population-based cohort of 61,377 men, ages 40 to 74 years. A job-exposure matrix, constructed by industrial hygienists specifically for the study population, was used to derive cumulative benzene exposure from all jobs held.

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The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P < 0.

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  • * The newly developed multi-ancestry PRS showed a strong correlation with LUAD risk, indicating that individuals in the highest PRS percentile had significantly increased risk compared to those in the lowest.
  • * Findings suggest that those in the highest risk category have a lifetime risk of about 6.69%, and they reach the average population's 10-year risk for LUAD by age 41, highlighting the importance of multi-ancestry PRS for better risk assessment in this group.
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Background: Metabolomics may reveal novel biomarkers for coronary heart disease (CHD). We aimed to identify circulating metabolites and construct a metabolite risk score (MRS) associated with incident CHD among racially and geographically diverse populations.

Methods: Untargeted metabolomics was conducted using baseline plasma samples from 900 incident CHD cases and 900 age-/sex-/race-matched controls (300 pairs of Black Americans, White Americans, and Chinese adults, respectively), which detected 927 metabolites with known identities among ≥80% of samples.

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  • - The study investigates how genetic variants affect the relationship between heavy alcohol consumption and the risk of pancreatic cancer, utilizing data from a sizable European ancestry population.
  • - Researchers identified a new relevant genomic region (10p11.22) linked to pancreatic cancer risk and a specific SNP (rs7898449) that suggests this association is influenced by heavy alcohol consumption.
  • - The findings highlight the potential role of the neuropilin 1 gene in pancreatic cancer development, offering new insights into cancer risk factors, especially among heavy drinkers.
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Identifying risk protein targets and their therapeutic drugs is crucial for effective cancer prevention. Here, we conduct integrative and fine-mapping analyses of large genome-wide association studies data for breast, colorectal, lung, ovarian, pancreatic, and prostate cancers, and characterize 710 lead variants independently associated with cancer risk. Through mapping protein quantitative trait loci (pQTL) for these variants using plasma proteomics data from over 75,000 participants, we identify 365 proteins associated with cancer risk.

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Biliary tract cancer (BTC) is a rare and aggressive malignancy with increasing incidence. Most BTC cases are diagnosed with metastatic disease which carries a 5-year survival rate of <5%. Physical activity, diet, and obesity might be associated with BTC risk, but studies have been limited particularly in African descendants.

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Breast cancer includes several subtypes with distinct characteristic biological, pathologic, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate the development of improved prevention and treatment approaches. In this study, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case genome-wide association study (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium.

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Alternative polyadenylation (APA) modulates mRNA processing in the 3'-untranslated regions (3' UTR), affecting mRNA stability and translation efficiency. Research into genetically regulated APA has the potential to provide insights into cancer risk. In this study, we conducted large APA-wide association studies to investigate associations between APA levels and cancer risk.

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