Yin Cao

Background and Aims The microbiome has long been suspected of a role in colorectal cancer (CRC) tumorigenesis. The mutational signature SBS88 mechanistically links CRC development with the strain of Escherichia coli harboring the pks island that produces the genotoxin colibactin, but the genomic, pathological and survival characteristics associated...

Serrated polyps (SPs) are precursors for colorectal cancer (CRC) and contribute disproportionately to post-colonoscopy cancers. Leveraging three US cohorts (43974 women and 5322 men), we developed prediction models for high-risk SPs (sized ≥10 mm or ≥3) among individuals undergoing their first colonoscopy screening. We then validated the model in t...

Introduction: Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding h...

Background The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular character...

Background: Previous studies on the relationship between fructose intake and cardiometabolic biomarkers have yielded inconsistent results, and the metabolic effects of fructose are likely to vary across food sources such as fruit versus sugar-sweetened beverages (SSB). Objectives: We aimed to examine associations of fructose from 3 major sources...

Purpose: Early-onset colorectal cancer (CRC diagnosed before age 50) has risen worldwide, with an increasing number of survivors of reproductive age. We aimed to investigate the risk of adverse pregnancy and neonatal outcomes among early-onset CRC survivors. Methods: We conducted a nationwide case-control study of 207 births in women with early-ons...

A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are as...

PURPOSE To prospectively examine the association between clonal hematopoiesis (CH) and subsequent risk of lung cancer. METHODS Among 200,629 UK Biobank (UKBB) participants with whole-exome sequencing, CH was identified in a nested case-control study of 832 incident lung cancer cases and 3,951 controls (2006-2019) matched on age and year at blood d...

Background: Evidence suggests that, compared to later-onset colorectal cancer (CRC), early-onset CRC (diagnosed before 50 years of age) occur more frequently in rectal location and less frequently in proximal colon location. Studies also indicate heterogeneity of molecular characteristics within early-onset CRCs and between early-onset and later-on...

OBJECTIVE We evaluated prospectively the association between incident early-onset (diagnosed before 40 years of age) and later-onset type 2 diabetes and early-onset (diagnosed before 50 years of age) and later-onset cancer risk. RESEARCH DESIGN AND METHODS We prospectively followed 228,073 eligible participants in the Nurses’ Health Studies for up...

Metabolic syndrome may contribute to the rising incidence of multiple gastrointestinal (GI) cancers in recent birth cohorts. However, other than hepatocellular carcinoma, the association between nonalcoholic fatty liver disease (NAFLD) and risk of non-liver GI cancers is unexplored. We prospectively examined the associations of NAFLD risk with GI c...

Background & Aims Interval colorectal cancers (CRC), cancers diagnosed after a screening/surveillance exam in which no cancer is detected, and before the date of next recommended exam, reflect an unprecedented challenge in CRC detection and prevention. To better understand this poorly characterized CRC variant, we examined the clinical and mutation...

Background & aims: The use of proton pump inhibitors (PPIs) has rapidly increased in the past two decades. Concerns about the regular use of PPIs contributing to mortality have been raised. Methods: We conducted a prospective cohort study using data collected from the Nurses' Health Study (2004-2018) and the Health Professionals Follow-up Study...

Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and...

Importance: In the past 4 years, the American Cancer Society and the US Preventive Services Task Force updated recommendations to initiate colorectal cancer (CRC) screening at 45 years of age to address the increasing incidence of CRC among adults younger than 50 years. However, empirical evidence evaluating the potential benefits of screening in...

Background: Recent preclinical research strongly suggests that dietary sugars can enhance colorectal tumorigenesis by direct action, particularly in the proximal colon that unabsorbed fructose reaches. Objectives: We aimed to examine long-term consumption of sugar-sweetened beverages (SSBs) and total fructose in relation to incidence and mortali...

Background The link between oral diseases and mortality remains under-explored. We aimed to evaluate the associations between tooth count, untreated caries and risk of all-cause and cause-specific mortality. Methods Data on 24 029 adults from the National Health and Nutrition Examination Survey 1988–94/1999–2010, with mortality linkage to the Nati...

Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtype...

Background Diverticulitis and cardiovascular disease (CVD) are two highly prevalent disorders sharing common risk factors which are hypothesized to have an inflammatory basis.AimsTo examine the association between history of diverticulitis and risk of incident CVD.Methods We conducted a prospective cohort study of 43,904 men aged 40 to 75 years wit...

Background Despite heightened interest in early-onset colorectal cancer (CRC) diagnosed before age 50, little is known on immune cell profiles of early-onset CRC. It also remains to be studied whether CRCs diagnosed at or shortly after age 50 are similar to early-onset CRC. We therefore hypothesized that immune cell infiltrates in CRC tissue might...

Background: Incidence of colorectal cancer (CRC) among individuals aged less than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk...

Introduction: Antibiotic use has emerged as a risk factor for colorectal neoplasia and is hypothesized as a contributor to the rising incidence of colorectal cancer under age 50 years or early-onset colorectal cancer (EOCRC). However, the impact of antibiotic use and risk of EOCRC is unknown. Methods: We conducted a population-based case-control...

Prospective data examining the association of aspirin use, according to dose and duration, with long-term risk of gastric adenocarcinoma in non-Asian cohorts are lacking. We evaluated the association between aspirin use and risk of gastric adenocarcinoma in two large prospective U.S. cohort studies, the Nurses' Health Study and the Health Professio...

Background & Aims In patients with celiac disease, gluten triggers an immune reaction that damages small intestinal villi and may increase long-term risk of gastrointestinal cancer. However, the health impacts of gluten in the general population are understudied. We aimed to examine the association between gluten intake and risk of digestive system...

Children and adolescents spend a substantial amount of time being sedentary. The impact of prolonged sedentary patterns on fat distribution has not been elucidated especially in the context of physical activity level. Our objective is to examine the independent and joint associations of prolonged sedentary patterns and physical activity level with...

Introduction: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum an...

Background & aims: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. Metho...

Background. Lung cancer is the second most common malignancy and the leading causes of cancer death in both men and women in the United States. Cross-sectional studies on sleep disorders showed that sleep apnea and nocturnal hypoxemia are associated with an increased risk of lung cancer. Studies on sleep patterns are largely limited to sleep durati...

Background: The incidence of early-onset colorectal cancer (EO-CRC) diagnosed under age 50 continues to rise, and the pattern shows a strong birth cohort effect. Sugar-sweetened beverage (SSB) consumption had substantially increased across successive birth cohorts until 2000, and the population under age 50 has the highest level of consumption. Des...

Background & Aims Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age 50. Methods We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among...

Background A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of l...

Background Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC while large-scale comprehensive analysis is lacking. Methods A total of 9,789 CRC cases and 11,231 controls of European ancestry from 11 observational studies were included. We harmo...

Objective: Early-onset colorectal cancer (CRC) is increasing in many developed countries. Type 2 diabetes mellitus has increased substantially in younger adults; however, its role in early-onset CRC remains unidentified. Design: We conducted a claims-based nested case-control study using IBM MarketScan Commercial Database (2006-2015). Incident earl...

Importance: Gluten avoidance has been suggested as having a benefit to cognitive health among the general population, given the link between gluten and cognitive impairment in patients with celiac disease. However, data are lacking in individuals without celiac disease. Objective: To examine whether gluten intake is associated with cognitive fun...

Importance Evidence indicates that screening for colorectal cancer (CRC) beginning at 50 years of age can detect early-stage CRC and premalignant neoplasms (eg, adenomas) and thus prevent CRC-related mortality. At present, the US Preventive Services Task Force recommends continuing CRC screening until 75 years of age and individualized decision-mak...

Objective Sugar-sweetened beverage (SSB) consumption had substantially increased across successive US birth cohorts until 2000, and adolescents and young adults under age 50 years have the highest consumption. However, the link between SSBs and early-onset colorectal cancer (EO-CRC) remains unexamined. Design In the Nurses’ Health Study II (1991–2...

Evidence indicates the pathogenic role of epigenetic alterations in early-onset colorectal cancers diagnosed before age 50. However, features of colorectal cancers diagnosed at age 50-54 (hereafter referred to as "intermediate-onset") remain less known. We hypothesized that tumor long interspersed nucleotide element-1 (LINE-1) hypomethylation might...

Background & aims Recent increasing trends in early-onset colorectal cancer (CRC) strongly supports that early-life diet is involved in CRC development. However, data are lacking on the relationship with high sugar intake during early-life. Methods We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added s...

Heavy alcohol consumption in mid-adulthood is an established risk factor of colorectal cancer (CRC). Alcohol use in early adulthood is common, but its association with subsequent CRC risk remains largely unknown. We prospectively investigated the association of average alcohol intake in early adulthood (age 18–22) with CRC risk later in life among...

Importance Although aspirin is recommended for the prevention of colorectal cancer (CRC) among adults aged 50 to 59 years, recent data from a randomized clinical trial suggest a lack of benefit and even possible harm among older adults. Objective To examine the association between aspirin use and the risk of incident CRC among older adults. Desig...

Objective The etiology of diverticulitis is poorly understood. The long-held belief that constipation and low-fiber diet are risk factors for diverticulosis has recently been challenged by studies that suggest that more frequent bowel movements predispose to diverticulosis. We aim to prospectively explore the association between bowel movement freq...

Background Higher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor. Methods In 27,196 females from the Nurses’ Health...

Objectives: Glucosamine and chondroitin supplements have been associated with reduced inflammation, as measured by C-reactive protein (CRP). It is unclear if associations vary by formulation (glucosamine alone vs. glucosamine+chondroitin), form (glucosamine hydrochloride vs. glucosamine sulfate), or dose. Design, Subjects, Setting, Location: The a...

The incidence of early-onset colorectal cancer (CRC), which occurs in individuals <50 years of age, has been increasing worldwide and particularly in high-income countries. The reasons for this increase remain unknown but plausible hypotheses include greater exposure to potential risk factors, such as a Western-style diet, obesity, physical inactiv...

OBJECTIVE To examine the associations of adolescent sugar-sweetened beverage (SSB) and sugar intake with risk of colorectal cancer (CRC) precursors. DESIGN Prospective cohort study. SETTING Nurses’ Health Study II (1998-2015), United States. PARTICIPANTS 33106 women who completed a validated high school food frequency questionnaire about adolesc...

Background The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed under age 50 has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. Methods In a prospective cohort study (Nurses’ Health Study II), we evaluated two empirical dietary patterns...

Background: Studies have shown an inverse association between use of glucosamine and chondroitin supplements and colorectal cancer risk. However, the association with the precursor lesion, colorectal adenoma and serrated polyp, has not been examined. Methods: Analyses include 43,163 persons from the Nurses' Health Study (NHS), Health Professiona...

Objective: Factors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined. Design: We conducted a nested case-control study among participants aged 18-64 in the IBM Mark...

Introduction: Tooth loss increases the risk of cardiovascular disease (CVD). However, its association with overall and cancer mortality, especially according to social gradient and smoking status, remains underexplored. Dental caries has recently emerged as a risk factor for CVD, but its association with mortality has not been well studied. This st...

Introduction: Early-onset colorectal cancer (CRC), as defined by CRC diagnosed before age 50, has been increasing in the past 2 decades, with unidentified reasons. Type 2 diabetes increases risk of CRC with average age of onset, however, epidemiological data linking type 2 diabetes and risk of early-onset CRC is thus far limited. Methods: To examin...

Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and...

Background Use of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a la...

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional g...

Objective: Although dysbiosis of the oral microbiome has been implicated in the development of periodontal disease, tooth loss, esophageal and gastric cancer, epidemiologic evidence regarding oral health and the 2 cancers is largely inconsistent. Design: We prospectively assessed the association of periodontal disease and tooth loss with risk of e...

1571 Background: The etiology and contributors to the rising incidence of early-onset colorectal cancer (CRC diagnosed under age 50), driven largely by distal and rectal cancer, remain largely unknown. Metabolic syndrome is associated with higher risk of CRC diagnosed at older ages; however, its association with early-onset CRC remains unclear. Met...

Background: Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods: We pooled data on tumor subtypes (microsatellite...

Background & aims: Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H2S), have been associated with development of colorectal cancer (CRC). We identified a dietary pattern associated with sulfur-metabolizing bacteria in stool and then investigated its association with risk of incident CRC using...

Background Increased mortality associated with low cardiorespiratory fitness has shown to take effect during late adulthood in previous generations. A recent rise in early death was observed in the US. We investigated the impact of low cardiorespiratory fitness during young and middle adulthood on premature death in healthy adults from recent gener...

Rationale The overuse of antibiotics has been an important clinical issue, and antibiotic exposure is linked to alterations in gut microbiota, which has been related to risks of various chronic diseases such as cardiovascular disease and cancer. Also, duration of antibiotic exposure may be a risk factor of premature death. Objective We investigate...

Background & aims: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk var...

Background & aims: Lifestyle and dietary risk factors for diverticulitis have also been associated with chronic inflammation. We performed a prospective study of associations among inflammatory potential of diets, circulating markers of inflammation, and the incidence of diverticulitis. Methods: We followed 46,418 men, initially free of divertic...

Objectives: Although low fiber intake has been considered a risk factor for diverticulitis, prospective evidence is limited in women despite having a disproportionate burden of disease, with little known about variation in the protective effects according to food sources. We assessed the associations of intakes of fiber and major food sources of f...

In Reply We appreciate the 2 valuable comments by Dr Mezuk and Dr Venniyoor that bring attention to the diverse and intertwined aspects of the rising incidence of obesity and early-onset colorectal cancer (CRC). Among US adults 20 years or older, obesity increased from 15% in 1980 to 40% in 2016.¹,2 Therefore, obesity is clearly not ubiquitous. Mor...

Background: A preventive potential of high calcium intake against colorectal cancer has been indicated for distal colon cancer, which is inversely associated with high-level CpG island methylator phenotype (CIMP), high-level microsatellite instability (MSI), and BRAF and PIK3CA mutations. In addition, BRAF mutation is strongly inversely correlated...