Cancer Epidemiology Biomarkers & Prevention最新文献

Background: The metabolomics approach using blood samples from epidemiologic studies has the potential to elucidate pathways or uncover biomarkers for breast cancer outcomes. Therefore, understanding the within-person reproducibility of the blood metabolome and the factors that influence metabolite levels over time in breast cancer survivors are crucial, but these remain largely unknown.

Methods: We estimated the within-person reproducibility of plasma metabolites in 61 Black breast cancer survivors from the Women's Circle of Health Follow-Up Study. Samples were collected from each participant at two time points, approximately 2 and 3 years after diagnosis. Untargeted metabolomic profiles were analyzed by Metabolon using ultrahigh-performance LC/MS-MS. We calculated the intraclass correlation coefficients (ICC) for each metabolite by dividing the between-person variance by the total variance. ICCs were compared across preanalytic factors (e.g., fasting) and participant characteristics using the Wilcoxon test.

Results: Among 857 named metabolites, the median ICC was 0.58 (IQR: 0.44-0.70). Of the metabolites, 16.6% showed high within-person reproducibility (ICC ≥ 0.75), spanning all metabolite classes, whereas 65.6% had an ICC within 0.4 to 0.75, and 17.9% had an ICC < 0.4. Reasonable ICCs were also observed for nonfasting samples (median 0.53, IQR: 0.39-0.67), although lower than those for fasting samples (median 0.63, IQR: 0.45-0.77). ICCs were slightly lower in younger, nonobese participants and in women with estrogen receptor-positive breast cancer.

Conclusions: The within-person reproducibility of plasma metabolites over 1 year among breast cancer survivors was generally acceptable.

Impact: A single-timepoint measurement could be useful in evaluating associations between metabolites and breast cancer outcomes.

Background: The impact of changes in physical activity (PA) after cancer diagnosis on prognosis remains unclear. This study evaluated mortality risks according to changes in PA from prior to diagnosis to after diagnosis among cancer survivors.

Methods: This population-based retrospective cohort study used the Korean National Health Insurance Service database. The study included 215,191 participants (125,756 men and 89,435 women) diagnosed with cancer between 2009 and 2017. PA, measured as the total of various light-, moderate-, and vigorous-intensity activities, was assessed prior to and after diagnosis. Deaths were ascertained between 2009 and 2019. All-cause and cancer-specific mortality risks were assessed according to PA changes using Cox proportional hazards regression.

Results: Following cancer diagnosis, active patients accounted for 63.30% of men and 55.29% of women, increasing from 54.04% and 43.35% prior to diagnosis. Compared with the consistently inactive group, all-cause mortality risks were significantly lower in patients who became active after diagnosis [adjusted HR (95% confidence intervals): men, 0.82 (0.79, 0.85); women, 0.87 (0.82, 0.93)] and in the consistently active group [men, 0.77 (0.74, 0.80); women, 0.81 (0.76, 0.86)]. Lower mortality risks were observed across cancer stages in men and localized/regional stages in women. PA and all-cause mortality had a dose-response association. PA was inversely associated with all-cause or cancer-specific mortality in men with gastric, colorectal, liver, and lung cancers and women with colorectal cancer.

Conclusions: Being physically active after diagnosis is associated with reduced all-cause mortality among cancer survivors in a dose-response manner, regardless of PA levels prior to diagnosis.

Impact: PA should be promoted as a standard component of cancer care to improve prognosis.

Background: Historical redlining was a 1930s residential segregation policy, in which neighborhoods were graded according to race, class, and land use. As contemporary neighborhood profiles differ according to historical redlining grade, historical redlining may contribute to current breast cancer disparities. We evaluated whether historical redlining grade is associated with overall 5-year survival in a cohort of breast cancer cases in New York State. We hypothesize that worse redlining grade is associated with lower survival.

Methods: This New York State Cancer Registry-based cohort included 60,773 breast cancer cases diagnosed between 2008 and 2018 and in a census tract at diagnosis with a historical redlining grade. Cases were assigned a grade: A (best) to D (hazardous). Cox models estimated HRs for 5-year mortality associated with historical redlining grade. We stratified models by case factors and neighborhood characteristics.

Results: Five-year survival displayed a significant gradient with historical redlining (P < 0.001). Compared with A-grade, residence in B-grade, C-grade, and D-grade neighborhoods was associated with a 29%, 37%, and 64% increase in mortality, respectively (P < 0.001). Associations persisted after adjustment for health insurance and treatments. Elevated risk associated with D-grade was specifically observed among non-Hispanic White cases, local and regional stages, hormone receptor-positive tumors, non-triple-negative cases, and across neighborhood characteristics. We found significant interaction with redlining grade for race/ethnicity and neighborhood characteristics.

Conclusions: Historical redlining was associated with progressively lower survival for each grade among breast cancer cases. Associations are not fully explained by healthcare factors or contemporary neighborhood characteristics.

Impact: Historical redlining has lasting effects on contemporary breast cancer survival.

Background: Retrospective reporting of cigarette use can affect the accuracy of outcomes in tobacco treatment trials. The inclusion of objective measures of smoking, such as biomarkers of nicotine and tobacco exposure, is recommended. Most trials examining biomarkers after a behavioral intervention have included predominantly White adults enrolled in cessation, versus reduction, trials. The current study examined biomarkers of nicotine and tobacco exposure within a harm reduction trial in Black adults who smoke (AWS).

Methods: Nontreatment-seeking socioeconomically disadvantaged Black AWS (N = 65) were randomized to a treatment-as-usual control or enhanced care single-session intervention aimed to reduce their smoking. Biospecimens were collected at baseline and 1 month after treatment to measure objective markers of nicotine and smoke exposure, including expired carbon monoxide, urinary metabolites of nicotine (cotinine and trans-3'-hydroxycotinine), and urinary tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.

Results: Those in the enhanced care condition self-reported a significant reduction in smoking at follow-up (P < 0.01), but there were no concomitant decreases across biomarkers (all P values > 0.05). Exploratory analyses in participants who reported at least 50% smoking reductions or reduced daily cigarette intake by at least three cigarettes at follow-up compared with baseline revealed nonsignificant changes across all biomarkers (all P values > 0.05).

Conclusions: Self-reported smoking reductions were not biochemically verified across measures. It is possible that compensatory behaviors when reducing smoking (e.g., deeper inhalations) or underreporting of smoking contributed to this discrepancy.

Impact: Partial smoking reduction does not seem to reduce biomarkers of carcinogen exposure and may not be an effective strategy to narrow tobacco-related health disparities in Black AWS.

Background: Telomere length attrition has been proposed as a mediator through which the adverse neighborhood social and environmental context affects cancer risk through stress-related pathways, but associations have been inconsistent. We examined associations between neighborhood social and environmental factors in a population with extensive capture of behavioral factors and comorbidities.

Methods: Data were pooled from nested case-control studies using blood samples collected in two large prospective US-based cohorts of male (n = 3,065) and female (n = 9,993) health professionals. Relative leukocyte telomere length was assayed using qPCR and geospatial measures of socioeconomic status, air pollution, green space, and temperature were linked to participants' address at blood draw.

Results: After adjusting for sociodemographic and lifestyle covariates, no statistically significant associations of relative leukocyte telomere length with any of the address-level neighborhood socioeconomic or environmental factors were observed.

Conclusions: In this large nation-wide cross-sectional study of male and female health professionals in the United States, neighborhood social and environmental contextual factors were not associated with telomere length.

Impact: Further cross-sectional studies of associations between neighborhood social and environmental factors and telomere length are unlikely to improve understanding of this potential mediating mechanism. Studies with repeated measures may be required.

Background: We previously demonstrated differences in treatment and mortality between non-Hispanic Black (NHB) and non-Hispanic White (NHW) women with triple-negative breast cancer (TNBC). The impact of residential segregation on TNBC treatment and outcomes remains unknown.

Methods: We identified NHB and NHW women with TNBC diagnosed from 2010 to 2015 and followed through 2016, using the Surveillance, Epidemiology, and End Results dataset. County-level racialized economic segregation was measured using the index of concentration at the extremes. Multilevel Cox regression and multilevel logistic regression accounting for county-level clustering were used to calculate HRs and ORs.

Results: Of 25,217 patients, 25.6% were NHB. Compared with patients in counties with the highest concentration of high-income NHW residents (most privileged), patients in counties with the highest concentration of low-income NHB residents (most deprived) had significantly higher risks of breast cancer-specific mortality [HR = 1.14; 95% confidence interval (CI), 1.01-1.30; Ptrend = 0.12], overall mortality (HR = 1.15; 95% CI, 1.02-1.29; Ptrend = 0.06), and late-stage diagnosis (OR = 1.15; 95% CI, 1.01-1.32; Ptrend = 0.03). Overall, 28.2%, 24.5%, and 18.3% of excess risks of breast cancer mortality, overall mortality, and late-stage diagnosis in NHB (vs. NHW) patients were explained by residential segregation. There was no significant association between residential segregation and treatment.

Conclusions: Living in the most deprived versus privileged neighborhoods was associated with lower likelihoods of early detection and survival of patients with TNBC, contributing to TNBC outcome disparities between NHBs and NHWs.

Impact: This highlights the importance of breast cancer screening for neighborhoods with predominantly low-income NHB residents and elucidating the pathways linking segregation to TNBC prognosis.

Background: The benefit-to-harm ratio of PSA-based prostate cancer screening may be improved through implementation of PSA reference ranges that consider innate individual characteristics. We evaluated variation in PSA levels by factors that may influence PSA levels among men eligible to undergo prostate cancer screening.

Methods: We identified men ages 40 to 79 years in the All of Us Research Program who had no history of prostate cancer or elevated PSA at cohort enrollment. PSA distributions were compared across age groups, self-identified race or ethnicity (SIRE), body mass index (BMI), polygenic risk score (PRS) for prostate cancer risk, and PRS for PSA level. Multivariable associations between these factors and PSA percentiles were evaluated using quantile regression.

Results: Among 13,749 eligible men, 95th percentiles (p95) of PSA values increased with age (40-49 years: 1.81 ng/mL, 50-59 years: 3.23 ng/mL, 60-69 years: 4.15 ng/mL, and 70-79 years: 5.53 ng/mL). p95 of PSA was 0.83 ng/mL lower [95% confidence interval (CI), 0.44-0.1.22] among participants with BMI 35 to 39 kg/m2 versus <25 kg/m2. p95 of PSA was 2.32 ng/mL higher (95% CI, 1.20-3.44) among those with PRS for prostate cancer >90th percentile versus ≤50th percentile and 1.21 ng/mL higher (95% CI, 0.50-1.92) among males with PRS for PSA >90th percentile versus ≤50th percentile. SIRE was not consistently associated with PSA levels.

Conclusions: PSA levels vary by age, BMI, and PRS but not SIRE. Further work is needed to understand how tailoring PSA reference ranges based on these characteristics would affect screening outcomes.

Impact: Consideration of factors that endogenously influence PSA levels may lead to improved benefit-to-harm ratios of prostate cancer screening.

Background: Cancer outcomes in people living with human immunodeficiency virus (PWH) may be driven in part by a distinct tumor microenvironment (TME) for cancers that develop in the setting of persistent immune dysfunction.

Methods: Tumor samples from PWH were retrospectively obtained from the AIDS Cancer Specimen Resource, Moffitt Cancer Center, and Huntsman Cancer Institute. Staining of 22 different tumor immune markers was compared between PWH and cancer and patients diagnosed with the same cancer type but without human immunodeficiency virus.

Results: A total of 292 samples were analyzed, with 51 samples obtained from PWH (lung cancer = 17; breast cancer = 14; and prostate cancer = 20). Cells positive for PD-1 were observed more frequently in PWH and lung cancer [OR, 1.88; 95% confidence interval (CI), 1.02-3.45], whereas CD11b+ cells were observed less frequently (OR, 0.4; 95% CI, 0.17-0.93). Three immune markers showed higher abundance in PWH and breast cancer, including PD-L1 (OR, 3.24; 95% CI, 1.52-6.91), CD14 (OR, 3.37; 95% CI, 1.14-10.0), and FOXP3 (OR, 1.91; 95% CI, 1.03-3.53). In PWH and prostate cancer, the abundance of five immune markers was higher, including PD-L1 (OR, 5.94; 95% CI, 3.77-9.34), whereas three markers had lower abundance including CD14 (OR, 0.40; 95% CI, 0.22-0.74), as well as CD16 and CD11c.

Conclusions: This pilot study showed that differences in the TME exist for PWH diagnosed with age-related non-AIDS-defining cancers. Future work evaluating TME differences in relation to clinical endpoints is needed.

Impact: Findings are consistent with the hypothesis of altered tumorigenesis for cancers developing in an environment of immunosuppression.

Background: Studying human papillomavirus (HPV) genotype concordance between male and female partners and between multiple anatomic sites can help our understanding of HPV epidemiology.

Methods: Heterosexual couples ages 18+ formed within the past 6 months attended visits at 0, 2, 4, 6, 9, and 12 months. They answered questionnaires and provided genital, oral, and anal samples for HPV genotyping. We calculated observed/expected (O/E) concordance [with 95% confidence intervals (CI)] between anatomic sites of HPV genotype-specific infections across all visits and cumulatively (i.e., ever-positivity). We used mixed-effects logistic regression with random intercepts at the person level to estimate ORs for concordance and to assess predictors of genital HPV detection and partner concordance.

Results: Within-individual O/E genital/anal concordance was 23.37 (CI, 15.55-38.05) for females and 14.79 (CI, 9.20-43.45) for males, whereas genital/genital O/E concordance between partners was 14.99 (CI, 12.47-18.41). Genital/genital concordance for ever-positivity within couples was substantial: O/E: 10.06 (CI, 8.55-12.12), with ORs of 70.75 (CI, 43.70-114.56) for females and 67.34 (CI, 41.96-108.06) for males. Significant predictors of genital ever-positivity were one's partner's ever-positivity, ORs of 66.2 (CI, 40.96-107.08) in females and 61.53 (CI, 38.19-99.14) in males, and age above the median in females and males, ORs of 1.66 (CI, 1.06-2.59) in females and 1.95 (CI, 1.30-2.91) in males. Concordance doubled (OR, 1.96; CI, 1.12-3.46) with occasions of intimacy above the median.

Conclusions: We observed substantial genital/anal concordance within individuals (particularly females) and genital/genital concordance between partners. Certain sociodemographic and behavioral factors influenced concordance.

Impact: Findings shed light on HPV natural history and transmissibility.

Background: Engagement in sun protection behaviors is low among young adults (ages 18-25 years). Efficacious sun safety interventions for this at-risk population and information on intervention engagement and costs are needed. The purpose was to conduct secondary analyses examining intervention implementation strategies and outcomes (e.g., engagement), intervention moderators, and costs of three digital interventions to increase sun protection behaviors previously evaluated for effectiveness in a randomized controlled trial.

Methods: The randomized controlled trial compared three conditions: a basic efficacious intervention, an enhanced version of the intervention, and an educational e-pamphlet. Sun protection measures, intervention engagement and implementation, putative moderators, and intervention costs were assessed through 1 year.

Results: Engagement (4.6 of 12 modules completed) was similar for basic and enhanced interventions. Engagement was significantly associated with sun protection. Men and individuals with lower tanning ability completed more modules than women and those with higher tanning ability. Enhanced was more effective than basic for men (but not women) through 1 year. After initial development, both active interventions were similar in cost per person at larger sample sizes.

Conclusions: Despite attempts at enhancement, engagement in basic and enhanced was similar. Although all interventions were costly to create, they were less costly to maintain and could be scaled up for dissemination. Based on both engagement and effects on sun protection, the enhanced intervention would be recommended for men, women, or both.

Impact: This digital intervention offers the potential to reduce skin cancer risk in a large population of US young adults.