Cancer Epidemiology Biomarkers & Prevention最新文献

Background: Residential segregation limits the access to resources, primarily because of disinvestment. This study evaluated the association between residential segregation and colorectal cancer screening in the United States and whether findings differed by race and ethnicity.

Methods: Restricted National Health Interview Survey data (2010-2018) were used to ascertain colorectal cancer screening adherence per US Preventive Services Task Force recommendations. Residential segregation was operationalized using the Index of Concentration at the Extremes (ICE), based on income, race, and ethnicity information obtained from the 2014 to 2018 American Community Survey estimates for counties. Multivariable logistic regression models with robust variance estimators accounting for within-county correlation were used. Analyses were stratified by race and ethnicity and weighted to represent the US population.

Results: In this cross-sectional study (n = 44,690), participants residing in less advantaged counties had lower colorectal cancer screening adherence than those residing in the most advantaged counties [Q1 vs. Q5, OR (95% confidence interval): ICE income, 0.77 (0.70-0.86); ICE race, 0.86 (0.77-0.96); ICE race + income, 0.75 (0.67-0.84)]. In analyses stratified by race and ethnicity, we observed that overall findings were mostly driven by White people and estimates were less precise with no clear gradients among racial and ethnic minoritized groups. Among Black participants, colorectal cancer screening did not vary across quintiles of economic segregation.

Conclusions: Residential segregation was associated with colorectal cancer screening.

Impact: Interventions aimed at improving colorectal cancer screening uptake in the United States should address structural barriers present in areas with higher concentrations of low-income minoritized racial and ethnic groups and how features of residential segregation might differentially affect racial and ethnic groups.

Background: Telomere length (TL) shortens with age and is associated with an increased risk of numerous chronic diseases. However, the causal direction of the association between TL and cancer risk remains uncertain. This study aimed to assess the causal impact of TL on cancer risk using Mendelian randomization (MR) analysis.

Methods: Genome-wide association studies from Singapore and China data, the Korean Cancer Prevention Study II (KCPS-II), the Korean Genome Epidemiologic Study, and the Biobank of Japan were utilized. A two-sample MR study was performed using summary-level genome-wide association study data from individuals of East Asian ancestry. SNPs associated with TL were used as instrumental variables.

Results: Longer TL per 1-SD increase due to germline genetic variants was associated with a higher risk of site-specific cancer. In the KCPS-II and Korean Genome Epidemiologic Study, the strongest association was observed with thyroid cancer {OR, 2.49 [95% confidence interval (CI), 1.79-3.47] and 2.27 (1.49-3.46)}, followed by lung cancer [OR, 2.19 (95% CI, 1.60-3.08) and 1.45 (1.12-1.87)]. Similar results were observed in the Biobank of Japan, with OR, 2.92 (95% CI, 1.75-4.88) for thyroid cancer and 2.04 (1.41-2.94) for lung cancer. In histologic subgroup analysis of KCPS-II, a significant relationship was found with lung adenocarcinoma [OR, 2.26 (95% CI, 1.55-3.31)] but not with lung squamous cell carcinoma (1.21, 0.47-3.06). After removing outlier SNPs in the radial MR analysis, significant associations were identified for both lung adenocarcinoma [OR, 1.88 (95% CI, 1.25-2.82)] and lung squamous cell carcinoma (2.29, 1.05-4.98).

Conclusions: Our findings suggest that longer TL increases the risk of various cancers in East Asian populations.

Impact: Genetically determined longer TL may contribute to a risk of certain cancers.

Background: Late bladder toxicity is a concern for patients receiving prostate cancer radiotherapy and negatively affects survivors. Few risk factors are known beyond the radiation dose and volume of bladder exposed. A polygenic risk score (PRS) could identify susceptible patients.

Methods: A PRS was built using genome-wide association results from the Radiogenomics Consortium (N = 3,988) and then tested in the prospective REQUITE and URWCI studies (N = 2,034). The primary outcome was time to patient-reported gross [grade ≥2, (≥G2)] hematuria, analyzed using Cox proportional hazards regression. Secondary outcomes were ≥G2 urinary retention and frequency. The PRS was externally validated for clinically diagnosed irradiation cystitis in the UK Biobank (N = 8,430). A gene-burden test evaluated rare coding variants.

Results: A 115-variant PRS was associated with a significantly increased risk of ≥G2 hematuria [hazard ratio (HR) per SD = 1.22; P = 0.009] as well as urinary retention (HR per SD = 1.18; P = 0.016) and frequency (HR per SD = 1.14; P = 0.036). When binarized, men in the upper decile (PRShigh) had a >2-fold increased risk of hematuria after adjusting for clinical risk factors [HR = 2.12; P = 0.002; Harrel's concordance index = 0.71 (95% confidence interval, 0.65-0.76)]. A similar effect size was seen in the UK Biobank for clinically diagnosed irradiation cystitis [odds ratio (OR) = 2.15; P = 0.026]. The burden test identified BOD1L1 as a putative novel radiosensitivity gene.

Conclusions: This PRS identifies susceptible patients and could guide the selection of those needing reoptimized treatment plans that spare the bladder beyond currently recommended constraints.

Impact: PRS-guided treatment planning in radiation oncology could lower the incidence of clinically relevant bladder toxicity and reduce the impact of this outcome on prostate cancer survivors.

Background: Children living in upstream oil and natural gas (O&G) areas may be exposed to leukemogens and at increased risk for acute lymphoblastic leukemia (ALL).

Methods: We conducted a case-control study of children born in Colorado between 1992 and 2019. We matched 451 children diagnosed with ALL at ages 2 to 9 years starting in 2002 to 2,706 controls based on birth month/year and Hispanic ethnicity. We estimated upstream O&G activity intensities from conception through a 10-year latency using our intensity-adjusted inverse distance weighted (IA-IDW) model. We applied logistic regression models adjusted for confounders to evaluate associations between ALL and IA-IDW.

Results: For children within 5 km of an O&G well site, we observed a 62% [OR = 1.62; 95% confidence interval (CI), 0.964-2.62], 84% (OR = 1.84; 95% CI, 1.35-2.48), and 100% (OR = 2.00; 95% CI, 1.14-3.37) increase in ALL risk for low, medium, and high IA-IDW groups, compared with the referent group. Within 13 km, we observed a 59% (OR = 1.59; 95% CI, 1.03-2.37), 40% (OR = 1.40; 95% CI, 1.09-1.80), and 164% (OR = 2.64; 95% CI, 1.80-3.86) increase in ALL risk for low, medium, and high IA-IDW groups.

Conclusions: Colorado's children living within 13 km of O&G well sites are at increased risk for ALL, with children within 5 km bearing the greatest risk. Current setbacks between O&G well sites and residences may not be sufficient to protect the health of these children.

Impact: Our results can be applied to policies to reduce childhood leukemogen exposures.

The use of smokeless tobacco and betel quid is a significant risk factor for head and neck cancer, posing a major global public health concern. This meta-analysis evaluates the impact of cessation of the use of these products on head and neck cancer risk to guide interventions. Case-control and cohort studies were found through PubMed, Scopus, and Embase databases. Two independent reviewers screened studies and then extracted data. RRs and 95% confidence intervals (CI) for different product cessation were calculated from raw data and meta-analyzed by using random-effects models. A total of 13 studies met the inclusion criteria. Findings were predominantly derived from Asian (n = 9) studies in which betel quid use is widespread. Results showed reduced head and neck cancer risk following cessation of betel quid use with (RR = 0.66; 95% CI, 0.54-0.81) or without tobacco (RR = 0.73; 95% CI, 0.56-0.95). However, other tobacco chewing products showed an RR of 1.07 (95% CI, 0.75-1.53). Long-term cessation (≥20 years) conferred substantial benefits (RR = 0.37; 95% CI, 0.22-0.61; risk estimates = 4). The study highlights the importance of cessation programs and targeted interventions to encourage smokeless tobacco quitting. Future research includes conducting detailed subgroup analyses based on cancer subsites and smokeless tobacco product types.

Background: Black Americans experience a higher incidence of colorectal cancer than Whites despite undergoing prevention screenings similar to those of Whites since 2010. We compared the colorectal adenoma status of Black and White patients at screening colonoscopy, a measure of colorectal cancer risk.

Methods: Using cross-sectional, observational data, we studied colorectal adenomas at first-time screening colonoscopy in average-risk patients aged 40 to 89 years, screened between September 2001 and July 2016 in South Carolina. We analyzed the age-adjusted odds of Black men and women (vs. White) having adenomas, advanced adenomas, ≥3 nonadvanced adenomas, and right hyperplastic polyps, and compared their total polyp burden (the sum of the diameters of all adenomas and right polyps detected).

Results: Among 28,100 patients (58.4% Black and 53.8% women), we found that Black patients had lower age- and gender-adjusted odds than White patients of having adenoma (OR = 0.88, P < 0.01) and right hyperplastic polyp (OR = 0.74, P < 0.01), with a similar pattern within gender groups. Black and White patients were similar about advanced adenoma and 3+ nonadvanced adenoma. Among patients with lesions, mean polyp burden ranged from 8.5 mm (±7.2) for Black women aged 40 to 49 years to 12.3 mm (±7.4) for Black men aged more than 70 years. Age-adjusted polyp burden was 0.4 mm higher for Black men than for White men and 0.3 mm lower for Black women than for White women patient groups (P < 0.01).

Conclusions: In a large, racially balanced patient sample, Black and White patients showed similar polyp profiles.

Impact: Given similar adenoma status, other evidence-supported clinical factors associated with suboptimal polyp detection should be explored to understand the continuing colorectal cancer disparities affecting Black Americans.

Background: Alcoholic beverages and the main metabolite of alcohol, acetaldehyde, are known carcinogens. A genetic variant in aldehyde dehydrogenase 2 (ALDH2, G>A, rs671) leads to decreased efficiency in metabolizing acetaldehyde and is associated with an increased cancer risk. As alcohol consumption is a modifiable risk factor for various cancers, the identification of ALDH2 deficiency presents an opportunity for precision cancer prevention.

Methods: Our primary objectives were to examine the prevalence of ALDH2 deficiency and alcohol consumption behavior among affected individuals within a large, diverse US national cohort. The prevalence of ALDH2 deficiency was determined by examining the rs671 genotype among 311,290 participants within the All of Us Research Program. Relationships among self-reported alcohol consumption, sociodemographic factors, and the rs671 genotype were analyzed.

Results: ALDH2 deficiency was most prevalent among individuals who identified as Asian, among whom 23.5% had at least one deficient ALDH2 allele compared with <2.5% in all other racial/ethnic groups. Among those with one and two deficient ALDH2 alleles, 61.2% and 24.4% reported drinking in the past year, respectively, and of these, 30.3% and 16.0% reported binge drinking. Multivariable analysis showed that ALDH2 genotype, sex, age, race, education, income, employment, marital status, and country of birth were associated with alcohol consumption behavior.

Conclusions: Most individuals with ALDH2 deficiency reported drinking alcohol in the past year, and consumption was associated with various sociodemographic variables, particularly sex, age, and country of birth.

Impact: Our findings suggest a significant opportunity for precision cancer prevention targeting the unique prevalence of ALDH2 deficiency among Asian Americans.

Background: The heterogeneous biology of cancer subtypes, especially in lung cancer, poses significant challenges for biomarker development. Standard model building techniques often fall short in accurately incorporating various histologic subtypes because of their diverse biological characteristics. This study explores a nested biomarker model to address this issue, aiming to improve lung cancer early detection.

Methods: The study included 337 patients from two clinical sites. Blood biomarkers were analyzed and various statistical methods employed to develop a nested model. This model was designed to account for the biological heterogeneity across histologic subtypes, compared against traditional logistic regression models.

Results: The patient cohort included a range of malignant and benign nodules and included different cancer subtypes reflecting lung cancer heterogeneity. The nested model had comparable performance overall with the Mayo Clinic model and a standard logistic regression model with an AUC of 77.6 (95% confidence interval, 72.2-83.0) in training and 77.3 (95% confidence interval, 65.8-88.9) in testing. The nested subtype versus benign model had the best performance in the training set overall and had a particular advantage for small cell subtype prediction.

Conclusions: This study highlights the challenges cancer heterogeneity present for biomarker development and the potential for nested biomarker models to improve early cancer detection. Validation of this approach in larger cohorts is essential to prove its predictive benefit in biologically diverse cancers.

Impact: This work addresses the challenge of biological heterogeneity in biomarker development. A nested modeling approach may assist in developing more effective multicancer early detection strategies.

Background: Current evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer. However, the mediating role of the circulating metabolome in this relationship remains unclear.

Methods: Targeted metabolomics data from 6,055 participants in the European Prospective Investigation into Cancer and Nutrition cohort were used to identify metabolites associated with PA and derive a metabolomic signature of PA levels. PA levels were estimated using the validated Cambridge PA index based on baseline questionnaires. Mediation analyses were conducted in a nested case-control study (1,585 cases, 1,585 controls) to examine whether individual metabolites and the metabolomic signature mediated the PA-colorectal cancer association.

Results: PA was inversely associated with colorectal cancer risk (OR per category change: 0.90, 95% confidence interval, 0.83-0.97; P value = 0.009). PA levels were associated with 24 circulating metabolites after FDR correction, with the strongest associations observed for phosphatidylcholine acyl-alkyl (PC ae) C34:3 (FDR-adjusted P value = 1.18 × 10-10) and lysophosphatidylcholine acyl C18:2 (FDR-adjusted P value = 1.35 × 10-6). PC ae C34:3 partially mediated the PA-colorectal cancer association (natural indirect effect: 0.991, 95% confidence interval, 0.982-0.999; P value = 0.04), explaining 7.4% of the association. No mediation effects were observed for the remaining metabolites or the overall PA metabolite signature.

Conclusions: PC ae C34:3 mediates part of the PA-colorectal cancer inverse association, but further studies with improved PA measures and extended metabolomic panels are needed.

Impact: These findings provide insights into PA-related biological mechanisms influencing colorectal cancer risk and suggest potential targets for cancer prevention interventions.

Background: Although community engagement has had a substantial presence in public health research, community input to inform geospatial and health analyses remains underutilized and novel. This article reports on community engagement activities to solicit stakeholder perspectives on the role of neighborhood conditions in health and cancer. We discuss how this community input refined an a priori conceptual model to be tested in the larger Families, Friends, and Neighborhoods Study.

Methods: We conducted semistructured virtual interviews with 82 stakeholders (e.g., community and faith leaders, educators, and healthcare workers) across four states (Maryland, Connecticut, Alabama, and Missouri). Participants discussed the impact where a person lives can have on their health and cancer risk. We subsequently convened a virtual group discussion with 17 randomly selected interviewees. Our study team individually reviewed discussion notes, which were synthesized into a consensus document.

Results: In addition to constructs from the original conceptual model, participants identified neighborhood-level factors not present in the original model, including K-12 educational quality, local property investment, homelessness, public transportation infrastructure, proximity to healthcare facilities, environmental toxin exposures, access to healthy foods, and cost of living. These factors will be incorporated into the Families, Friends, and Neighborhoods Study analytic models.

Conclusions: Although geospatial analyses in health research have not traditionally employed community engagement techniques, this study illustrates the value of informing multilevel analytic models with the lived experiences of those negatively affected by neighborhood conditions that underlie the risk, prevention, and screening behaviors driving cancer incidence and mortality.

Impact: Future social epidemiology research can be enriched through community engagement.