Wen-Yi Huang

Associations of self-identified race and ethnicity and genetic ancestry with mortality among cancer survivors

Abstract Self-identified race and ethnicity (SIRE) and genetic ancestry are potentially associated with disparities in health outcomes; however, independent effects of SIRE and genetic ancestry on mortality in cancer survivors including when adjusting for multiple risk factors are understudied. Among 23 445 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian Screening Trial, SIRE was associated with mortality among prostate, colorectal, lung, ovarian, and breast cancer survivors; genetic ancestry was associated with mortality among prostate, colorectal, and breast cancer survivors. Associations were strong when adjusting for age at cancer diagnosis, sex, and tumor characteristics but attenuated when adjusting for individual-level factors and population-level socioeconomic status. For example, mortality risk was higher among Black vs White prostate cancer survivors and African genetic ancestry vs European genetic ancestry, but associations were attenuated after multilevel adjustment. Results suggest that SIRE and genetic ancestry do not solely reflect biologic variation; rather, social factors may drive mortality differences by SIRE and genetic ancestry.

The human oral microbiome and risk of colorectal cancer within three prospective cohort studies in the United States

AbstractBackgroundOral microbes detected in feces have been associated with colorectal cancer (CRC) in cross‐sectional studies. This study investigated the prospective associations between the oral microbiome and incident CRC in the Agricultural Health Study (AHS), National Institutes of Health–AARP (NIH‐AARP) Diet and Health Study, and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.MethodsIndividuals with oral samples collected before incident CRC diagnoses were identified in the AHS (N = 331), NIH‐AARP (N = 249), and PLCO (N = 446) and compared with referent subcohorts (N = 3431). The V4 region of the 16S ribosomal RNA gene was sequenced from oral wash DNA, and the data were processed with QIIME2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall CRC and by anatomic subsite (i.e., proximal colon, distal colon, and rectum) were estimated with Cox proportional hazards models with adjustment for potential confounders by cohort and then meta‐analyzed.ResultsOverall, no associations were found between microbial characteristics and CRC risk. However, associations were observed with alpha and beta diversity indices and individual genera in analyses stratified by anatomic subsite. For instance, the presence of Olsenella was strongly positively associated with distal colon cancer risk (HR, 2.16; 95% CI, 1.59–2.95), whereas the presence of Prevotella 2 was positively associated with rectal cancer risk (HR, 1.68; 95% CI, 1.14–2.46).ConclusionsThis large study of the prospective association between the oral microbiome and CRC risk showed numerous site‐specific associations, including multiple associations with distal colon and rectal cancer risk.

Association of alcohol intake over the lifetime with colorectal adenoma and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Abstract Background Alcohol drinking is associated with higher colorectal cancer (CRC) risk, but research on lifetime alcohol drinking is limited. The objective of the current study was to estimate the association of lifetime alcohol drinking with incident colorectal adenoma and cancer. Methods US adults enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial reported alcohol intake during four age periods. Average lifetime alcohol intake was calculated as average drinks per week from age 18 years until study baseline. Alcohol intake patterns were defined by past and current drinking frequency. Among 12,327 participants with a negative baseline screen, 812 had an adenoma on the second screen. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for incident adenoma. During 20 years of follow‐up, 1679 incident CRC cases occurred among 88,092 participants. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for CRC. Results Current drinkers with an average lifetime alcohol intake of 14 or more drinks per week, compared with one drink or less per week, had a higher risk of CRC (HR, 1.25; 95% CI, 1.01–1.53), especially rectal cancer (HR, 1.95; 95% CI, 1.17–3.28). Consistent heavy drinking versus light drinking was positively associated with CRC risk (HR, 1.91; 95% CI, 1.17–3.12). Compared with current drinkers averaging less than one drink per week, former drinkers had lower odds of nonadvanced adenoma (OR, 0.58; 95% CI, 0.39–0.84). Current drinkers averaging from seven to less than 14 drinks compared with less than one drink per week had a lower risk of CRC (HR, 0.79; 95% CI, 0.64–0.97), especially distal colon cancer (HR, 0.64; 95% CI, 0.42–1.00). Conclusions Consistent heavy alcohol intake and higher average lifetime alcohol drinking may increase CRC risk, whereas cessation may lower adenoma risk. Associations may differ by tumor site.

Weight Change and Incident Distal Colorectal Adenoma Risk in the PLCO Cancer Screening Trial

Abstract Background Although obesity is a known risk factor, the impact of weight change on colorectal adenoma risk is less clear and could have important implications in disease prevention. We prospectively evaluated weight change in adulthood and incident colorectal adenoma. Methods We assessed weight change during early-late (age 20 years to baseline, ie, ages 55-74 years), early-middle (20-50 years), and middle-late (50 years-baseline) adulthood using self-reported weight data in relation to incident distal adenoma in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (cases = 1053; controls = 16 576). For each period, we defined stable weight as greater than −0.5 kg to less than or equal to 1 kg/5 years, weight loss as less than or equal to −0.5 kg/5 years, and weight gain as greater than 1-2, greater than 2-3, or greater than 3 kg/5 years. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression; all tests were 2-sided. Results Compared with stable weight, weight loss during early-late adulthood was associated with reduced adenoma risk (OR = 0.54, 95% CI = 0.34 to 0.86), particularly among those who were overweight or obese at age 20 years (OR = 0.39, 95% CI = 0.18 to 0.84). Results were similar for early-middle adulthood but less pronounced for middle-late adulthood. Weight gain greater than 3 kg/5 years during early-late adulthood was associated with increased risk (OR = 1.30, 95% CI = 1.07 to 1.58, Ptrend < .001). Findings appeared stronger among men (OR for >3 kg/5 years = 1.41, 95% CI = 1.11 to 1.80) than women (OR = 1.09, 95% CI = 0.79 to 1.50, Pinteraction = .21). Conclusions Weight loss in adulthood was associated with reduced adenoma risk, particularly for those who were overweight or obese, whereas weight gain greater than 3 kg/5 years increased risk. Findings underscore the importance of healthy weight maintenance throughout adulthood in preventing colorectal adenoma.

GWAS Explorer: an open-source tool to explore, visualize, and access GWAS summary statistics in the PLCO Atlas

AbstractThe Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a prospective cohort study of nearly 155,000 U.S. volunteers aged 55–74 at enrollment in 1993–2001. We developed the PLCO Atlas Project, a large resource for multi-trait genome-wide association studies (GWAS), by genotyping participants with available DNA and genomic consent. Genotyping on high-density arrays and imputation was performed, and GWAS were conducted using a custom semi-automated pipeline. Association summary statistics were generated from a total of 110,562 participants of European, African and Asian ancestry. Application programming interfaces (APIs) and open-source software development kits (SKDs) enable exploring, visualizing and open data access through the PLCO Atlas GWAS Explorer website, promoting Findable, Accessible, Interoperable, and Re-usable (FAIR) principles. Currently the GWAS Explorer hosts association data for 90 traits and >78,000,000 genomic markers, focusing on cancer and cancer-related phenotypes. New traits will be posted as association data becomes available. The PLCO Atlas is a FAIR resource of high-quality genetic and phenotypic data with many potential reuse opportunities for cancer research and genetic epidemiology.

Associations of serum trimethylamine N‐oxide and its precursors with colorectal cancer risk in the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort

AbstractBackgroundDietary intake influences gut microbiome composition, which in turn may be associated with colorectal cancer (CRC). Associations of the gut microbiome with colorectal carcinogenesis may be mediated through bacterially regulated, metabolically active metabolites, including trimethylamine N‐oxide (TMAO) and its precursors, choline, L‐carnitine, and betaine.MethodsProspective associations of circulating TMAO and its precursors with CRC risk were investigated. TMAO, choline, betaine, and L‐carnitine were measured in baseline serum samples from 761 incident CRC cases and 1:1 individually matched controls in the prospective Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort using targeted fully quantitative liquid chromatography tandem mass spectrometry panels. Prospective associations of the metabolites with CRC risk, using multivariable conditional logistic regression, were measured. Associations of a priori–selected dietary exposures with the four metabolites were also investigated.ResultsTMAO and its precursors were not associated with CRC risk overall, but TMAO and choline were positively associated with higher risk for distal CRC (continuous ORQ90 vs. Q10 [95% CI] = 1.90 [CI, 1.24–2.92; p = .003] and 1.26 [1.17–1.36; p < .0001], respectively). Conversely, choline was inversely associated with rectal cancer (ORQ90 vs. Q10 [95% CI] = 0.77 [0.76–0.79; p < .001]). Red meat, which was previously associated with CRC risk in the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort , was positively associated with TMAO (Spearman rho = 0.10; p = .0003).ConclusionsSerum TMAO and choline may be associated with higher risk of distal CRC, and red meat may be positively associated with serum TMAO. These findings provide insight into a potential microbially mediated mechanism underlying CRC etiology.