Cancer Epidemiology Biomarkers & Prevention最新文献

Background: Observed neighborhood disinvestment is a chronic social determinant that is understudied in relation to cancer outcomes. This study investigated associations between neighborhood disinvestment, stage at diagnosis, and breast cancer-specific survival (BCSS) time.

Methods: Individual-level data included 844 women, diagnosed 2013 to 2019, from the Women's Circle of Health Follow-up Study, a population-based cohort of breast cancer survivors self-identifying as Black or African American. Neighborhood disinvestment was from a virtual audit of six indicators-garbage, graffiti, dumpsters, building conditions, yard conditions, and abandoned buildings-within 14,671 Google Street View streetscapes estimated at residential addresses using Universal Kriging. We fit accelerated failure time models of BCSS time as functions of neighborhood disinvestment by stage, adjusted for covariates (sociodemographic, lifestyle, and tumor- and treatment-related factors). Participants not experiencing an event at the end of follow-up (August 13, 2023) were right-censored.

Results: With a median follow-up time of 89 months, there were 91 breast cancer-specific deaths. Disinvestment and stage statistically interacted (P < 0.01). For stage III and stage II diagnoses, BCSS time decreased by 27% (95% confidence interval, 1%, 48%) and 37% (95% confidence interval, 5%, 58%), respectively, with each SD increase in disinvestment after adjustment for covariates. There was little evidence of associations between disinvestment and survival time among stages I and IV.

Conclusions: The tumor stage-dependent association between greater neighborhood disinvestment and shorter survival time could reflect chronic stress exposures suspected to adversely accumulate over time.

Impact: Neighborhood disinvestment might be an important, independent marker of social disadvantage impacting breast cancer survival.

Background: The goal of this article was to provide an overview of the current NCI-funded large cancer epidemiology survivor cohorts (CESC).

Methods: Large CESCs were defined as observational cohort studies following at least 1,000 cancer survivors over time and collecting data on survivorship outcomes. CESCs with NCI grant funding on June 1, 2024 were identified in two ways: (i) by identifying grants funded under cancer epidemiology cohort-relevant Notice of Funding Opportunities and (ii) by applying the Research, Condition, and Disease Categorization-indexed concepts related to cohorts to the entire NCI grant portfolio in the NIH's proprietary Query, View, Reporting System and reviewing grants identified via this search for inclusion.

Results: Thirty active grants supporting large CESCs were identified. Of the 30 CESCs, 36.7% are comprised of survivors of mixed cancer types; the remaining 63.3% are following survivors diagnosed with cancer of a single anatomic type or grouping (e.g., blood cancers). Special populations of focus include adult survivors of pediatric cancers, adolescent and young adult cancer survivors, pediatric cancer survivors, and stem cell transplant survivors. Notable gaps include cohorts following long-term cancer survivors, survivors of less common cancer types, and survivors from understudied populations.

Conclusions: CESCs highlighted in this article represent a substantial investment in exploring the multifaceted factors that influence cancer outcomes. These cohorts encompass an increasing diversity of cancer types, treatments, and populations.

Impact: CESCs provide valuable insights into clinical and molecular risk factors associated with cancer survivorship outcomes that inform guidelines and interventions.

Background: Recent genome-wide association studies (GWAS) have identified new susceptibility loci for melanoma, but their associations with multiple primary melanoma (MPM) are unclear.

Methods: We investigated the associations of 69 SNPs in 39 GWAS-identified loci with odds of MPM relative to single primary melanoma in the international, population-based Genes, Environment, and Melanoma study. Per-minor-allele ORs and 95% confidence intervals (CI) for individuals with MPM "cases" (n = 1,205) relative to single primary melanoma "controls" (n = 2,458) were estimated using multivariable logistic regression, and polygenic risk scores (PRS) were calculated and weighted based on a 2020 GWAS meta-analysis (57 of the 68 independent GWAS SNPs available).

Results: Thirteen SNPs in 11 gene regions (PARP1, CYP1B1/RMDN3, TERT, RAPGEF5, TYRP1, MTAP, CDKN2A/CDKN2B, KLF4, TYR, SOX6, and ASIP) were statistically significantly associated (P < 0.05) with MPM adjusting for age, sex, age-by-sex interaction, and study center. The highest versus lowest PRS quintile was associated with a 2.81-fold higher odds of MPM (95% CI, 2.10-3.78; P = 7.5 × 10-13); this association was attenuated but remained statistically significant after excluding SNPs individually associated with MPM (OR = 1.75, 95% CI, 1.32-2.31).

Conclusions: Inherited genetic variants spanning 11 gene regions were independently associated with MPM. Nonsignificant SNPs were associated with MPM when aggregated into a PRS, indicating that their cumulative effect may influence MPM risk despite lacking individual statistical significance in our study population.

Impact: Our findings provide additional evidence that these loci are associated with melanoma risk and estimate the magnitude of their genetic effect on subsequent (multiple) primary melanoma risk.

Background: We previously identified associations of esophageal adenocarcinoma risk with four inflammation-related candidate biomarkers: TNF receptor 2 (TNFR2), IL17A, VEGFR3, and resistin.

Methods: We aimed to replicate these candidates and discover novel associations with additional proteins. We conducted a nested case-control study of men with prediagnostic biospecimens stored at the US Department of Defense Serum Repository, including 203 incident esophageal adenocarcinoma cases. Controls were matched to cases in a ∼2:1 ratio by date of birth, race, service branch, and blood draw date. Multiplex immunoassays (Olink/Proseek panels) measured 254 proteins detected in ≥10% of all samples. Multivariable-adjusted conditional logistic regression models calculated associations between biomarker quantiles and esophageal adenocarcinoma. P values (<0.05) were used to indicate the statistical significance of candidates, and FDR was applied to the additional proteins. ORs from the current analysis and those from previous studies were combined for the candidate markers using fixed-effects meta-analysis.

Results: Among the four candidates, the highest category of TNFR2 was associated with significantly increased esophageal adenocarcinoma risk (ORQ4 vs. Q1 = 1.87; 95% confidence interval: 1.02-3.42). In the meta-analysis, associations with esophageal adenocarcinoma were positive for TNFR2 (meta-analyzed ORhighest-vs.-lowest = 2.04; 1.12-2.95) and inverse for IL17A (meta-analyzed ORhighest-vs.-lowest = 0.53; 0.26-0.80). Of the additional 250 proteins, 45 were associated with esophageal adenocarcinoma risk and 6 (monocyte chemotactic protein 3, IL6, TNFR1, hepatocyte growth factor, TFF3, and FURIN) remained significant after FDR correction.

Conclusions: We confirmed associations of TNFR2 and IL17A with esophageal adenocarcinoma risk. Additionally, our study expands the range of proteins associated with esophageal adenocarcinoma development.

Impact: This is the largest assessment to discover novel associations of inflammation-related proteins with esophageal adenocarcinoma to date.

Background: Understanding the change in emotional well-being (EWB) and functional well-being (FWB) in breast cancer survivors can facilitate targeted support for unmet needs.

Methods: Among 2,767 women with breast cancer in the Carolina Breast Cancer Study Phase 3, we assessed EWB and FWB with the Functional Assessment of Cancer Therapy - Breast instrument at 5 (baseline), 25, and 84 months after diagnosis. We identified well-being trajectories using latent class growth analysis, and relative frequency differences (RFD) with 95% confidence intervals (CI) were estimated for associations between trajectory group membership and demographic or clinical characteristics.

Results: Five trajectory groups were identified for both EWB and FWB. Most participants (∼70%) were classified into "good well-being" ("stable high" or "stable medium"). A small percentage (∼10%) fell into "very low baseline" or "early decrease", and the rest were "stable low" (∼20%). Overall, younger vs. older age was associated with "stable low" EWB (25.4% vs. 19.3%; RFD 6.1%; 95% CI, 3.0%-9.2%). Black participants more frequently had "stable low" FWB (24.2% vs. 16.6%; RFD 7.6%; 95% CI, 4.6%-10.6%). Breast cancer recurrence was strongly associated with "stable low" EWB (28.7% vs. 21.3%; RFD 7.3%; 95% CI, 2.3%-12.3%) and FWB (28.7% vs. 19.2%; RFD 8.6%; 95% CI, 3.7%-13.5%). Being unmarried, lower income, having nonprivate insurance, advanced stage, mastectomy vs. breast conservation surgery, and chemotherapy were also predictors of poor well-being trajectories.

Conclusions: Demographics and clinical features are associated with sustained poor well-being after breast cancer.

Impact: Improvements in long-term well-being may warrant targeted support.

Background: Colorectal cancer screening can reduce colorectal cancer risk, yet many men are not up to date with screening guidelines. Although previous qualitative studies have suggested links among anti-gay prejudice, traditional masculine self-concept, racial identity, and colorectal cancer screening among men, scholars have yet to fully explore these associations using quantitative data. This study used a nationally representative sample of Black and White men in the United States to test these associations and examine the sociodemographic correlates.

Methods: Using the National Opinion Research Center (NORC)/AmeriSpeak probability-based panel, we recruited a sample of Black and White men in the United States ages 45 to 74 years who had never been diagnosed with colorectal cancer (N = 909). Participants completed an online questionnaire measuring anti-gay prejudice, traditional masculine self-concept, sociodemographic variables, and screening-related outcomes (awareness of screening test options, screening intention, and adherence to screening recommendations).

Results: Black participants reported higher levels of anti-gay prejudice and traditional masculine self-concept than White participants. Anti-gay prejudice was associated with lower awareness and lower screening intention. Black participants reported higher intention to follow screening recommendations but not higher odds of actual adherence than White participants.

Conclusions: Men with anti-gay prejudice are less likely to be aware of colorectal cancer screening test options and less likely to intend to engage in colorectal cancer screening. The results have implications for the design and development of future interventions aimed at increasing colorectal cancer screening rates.

Impact: Future studies could develop targeted interventions and observe subsequent changes or conduct longitudinal studies to further explore the role of anti-gay prejudice in colorectal cancer screening.

Background: People living with HIV (PWH) have improved life expectancy because of effective human immunodeficiency virus (HIV) therapy but still experience immune impairment (e.g., altered CD4/CD8 T cells). We hypothesized that tumors diagnosed in PWH would have distinct molecular features.

Methods: We utilized whole-exome sequencing of paired tumor and germline DNA and RNA from 229 patients with cancer enrolled into the Oncology Research Information Exchange Network to classify total tumor mutation burden (TMB), MHC class I neoantigen count, and MHC class II neoantigen count.

Results: Specimens from 229 patients with cancer (110 PWH and 119 without HIV) were evaluated. Average TMB for tumors diagnosed in PWH was 249, compared with 172 for those without HIV. After adjustment for age, sex, race, smoking, and cancer site, the association between HIV and TMB remained statistically significant (OR = 1.72; 95% confidence interval (CI), 1.26-2.43). We further observed an association between HIV and higher putative class I neoantigen count (OR = 1.62; 95% CI, 1.10-2.41) but no association with putative class II neoantigens. When considering cancer sites separately in unadjusted analyses, average TMB was elevated in PWH for thyroid (P < 0.01) and bladder cancers (P = 0.03) and sarcoma (P = 0.04). Similarly, putative class I neoantigen count was elevated in PWH for head and neck (P < 0.01) and thyroid (P = 0.01) cancers, as well as sarcoma (P = 0.04).

Conclusions: Our findings indicate that tumors diagnosed in PWH harbor a higher TMB and a higher number of putative class I neoantigens.

Impact: A higher TMB in PWH may portend a more favorable response to certain cancer treatment modalities such as immune checkpoint inhibitors.

Background: Diffuse large B-cell lymphoma (DLBCL) is clinically heterogeneous, and gene expression profiling has identified at least two biologically distinct DLBCL subtypes defined by their cell of origin (COO): germinal center B cell (GCB) and activate B cell (ABC) or non-GCB. We evaluated a variety of putative DLBCL risk factors for etiologic heterogeneity by the COO in a clinic-based study of newly diagnosed DLBCL cases (N = 638) and frequency-matched controls (N = 2,253).

Methods: The COO was determined on formalin-fixed, paraffin-embedded tumor tissue, with DLBCL classified as GCB (N = 283), non-GCB (N = 188), or undetermined/missing (N = 167; mainly because of lack of tissue). Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).

Results: We identified heterogeneity by the COO for low socioeconomic status (SES), which was only associated with non-GCB DLBCL (OR = 1.88 for low vs. average SES; 95% CI, 1.08-3.27); alcohol use, which was only associated with GCB DLBCL (OR = 0.48 for former drinkers; 95% CI, 0.29-0.80 and OR = 0.47 for current drinkers; 95% CI, 0.32-0.71); and borderline heterogeneity for the regular use of regular/extra-strength aspirin, which was only associated with non-GCB DLBCL (OR = 0.36; 95% CI, 0.16-0.85). In contrast, there was no significant heterogeneity by the COO for family history, medical history, or other lifestyle factors.

Conclusions: Although requiring confirmation, most risk factors for DLBCL did not show etiologic heterogeneity by the COO, with some notable exceptions including alcohol use, SES, and perhaps regular use of regular/extra-strength aspirin showing associations.

Impact: Mechanistically, these findings suggest that most of the DLBCL risk factors evaluated here influence lymphomagenesis prior to differentiation into COO subtypes, with selected factors acting later.

Background: Research supporting the current recommendation to adhere to a healthy lifestyle following cancer diagnosis is limited. We investigated whether a healthy lifestyle after diagnosis is associated with a lower risk of mortality among those diagnosed with any malignant cancer and breast, colorectal, and prostate cancers.

Methods: In 2006 to 2010, UK Biobank participants (ages 37-73 years) were assessed. Analyses were restricted to those with a malignant cancer diagnosis prior to baseline (n = 20,805, including 5,845 breast, 1,943 colorectal, and 2,715 prostate cancer cases). Participants were followed for all-cause and cancer-specific death up to November 2022. A lifestyle index was determined based on lifestyle recommendations for cancer prevention. Cox regression was used to examine associations with all-cause and cancer-specific mortality among those with any cancer, and separately for breast, colorectal, and prostate cancers, adjusting for relevant confounders.

Results: There were 4,328 deaths and 3,354 cancer-specific deaths in the 258,985 person-years of follow-up. A higher lifestyle index, representing greater adherence to recommendations, was associated with a lower risk of all-cause mortality [any cancer - highest vs. lowest lifestyle index tertile: HR (95% confidence interval) = 0.77 (0.71, 0.83); breast: 0.75 (0.64, 0.88); colorectal: 0.68 (0.52, 0.89); and prostate: 0.73 (0.59, 0.89)] and cancer-specific mortality in all populations examined [any cancer: 0.82 (0.75, 0.89); breast: 0.88 (0.71, 1.09); colorectal: 0.58 (0.36, 0.94); prostate: 0.70 (0.53, 0.93)], although evidence was weaker for cancer-specific mortality among colorectal and breast cancer survivors.

Conclusions: Our findings provide evidence to support the recommendation to follow a healthy lifestyle after cancer diagnosis to prolong life.

Impact: Clinical guidelines and public health programs promoting a healthy lifestyle to cancer survivors may prolong life.

Background: Cervical cancer is the second leading cause of cancer death among women in Addis Ababa and other parts of Ethiopia. Yet, there are limited age-eligible city-wide data on cervical cancer screening prevalence in Addis Ababa to inform public policy.

Methods: A population-based cross-sectional study was conducted among 1881 screening eligible women aged 30 to 49 years, who were selected from 63 enumeration areas in Addis Ababa based on multistage sampling and proportional sample size allocation. Logistic regression was used to identify barriers to screening. All statistical tests were two-sided, P < 0.05.

Results: Overall, 30.8% [95% confidence interval (CI), 28.8%-33.0%] of study participants reported receipt of screening in the past 5 years. Less than half (45.7%) of women reported that they received healthcare provider recommendation for screening, and only 15% of married women reported that they had spousal support for it. In the multivariable adjusted model, the odd of being screened was considerably higher in women with healthcare provider recommendation, with spousal support, and with good cervical cancer screening awareness and knowledge of risk factors for the disease. Factors associated with not seeking screening service included feeling healthy and perception of low risk for cervical cancer.

Conclusions: Cervical cancer screening uptake is low in Addis Ababa, and less than half received healthcare provider recommendation. Future studies should identify barriers to provider recommendations.

Impact: The findings underscore the need for a coordinated effort to enhance healthcare provider recommendations for cervical cancer screening and to raise awareness about the benefits of screening in the general population.