Cancer Epidemiology Biomarkers & Prevention最新文献

Background: Fusobacterium nucleatum (Fn) has been associated with the risk of colorectal cancer, poor colorectal cancer survival, and tumor attributes. Accurate and sensitive detection of Fn in tumor tissue is critical for evaluating their role in colorectal cancer.

Methods: We developed a droplet digital PCR (ddPCR) assay for detecting Fn using the transcription termination/antitermination gene (nusG) normalized for host tissue (solute carrier organic anion transporter family member 2A1). We assayed Fn(nusG) in matched tumor and normal tissues for 613 participants in the Seattle site of the Colon Cancer Family Registry. We used logistic regression to determine the odds of Fn enrichment in tumor tissue according to the tumor site and stage, adjusting for age, sex, and body mass index.

Results: The limit of quantitation for Fn(nusG) was 4.1 copies/10 ng host tissue. Detection of Fn was quenched and poor at low levels in formalin-fixed, paraffin-embedded tissues using qPCR. There was a low agreement between qPCR and ddPCR (Cohen's kappa = 0.46). Fn(nusG) was detected in tumor (21%) and normal (10%) tissues and was enriched in 19% of tumors. Individuals with tumors enriched in Fn were more likely to be female (59% vs. 48%, respectively; P = 0.04) with proximal colon tumors (57% vs. 43%; P = 0.026). In multivariable-adjusted analyses, proximal colon tumors were significantly associated with Fn enrichment (OR vs. rectal tumors: 1.86; 95% confidence interval, 1.11-3.24).

Conclusions: We established a sensitive and specific method to detect Fn enrichment in human tissues.

Impact: ddPCR enhanced detection of Fn(nusG) for studies targeting tumor-associated bacteria.

Background: Endocrine-disrupting chemicals (EDC) found in many household and personal care products have hormonal properties and effects on the mammary gland. It is unclear whether urinary concentrations of EDCs are associated with higher percent breast density, a major risk factor of breast cancer.

Methods: We conducted a cross-sectional study of 97 college-aged women. We quantified individual levels of bisphenol A, bisphenol S, bisphenol F, triclosan, triclocarban, 3-benzophenone, seven phthalate metabolites, four parabens, and two other phenols in three 24-hour urine samples combined into a single pooled sample. Each woman had non-enhanced MRI to assess percent breast density. Associations between estimated concentrations of individual EDCs and percent breast density were analyzed using adjusted linear regression.

Results: There was no evidence of a statistically significant increase in mean percent breast density in the middle or highest tertile for any EDC measured. There was a suggestion that the mean percent breast density was elevated in individuals in the middle and highest tertile levels of ethyl paraben compared with those in the lowest tertile, with a relative increase in mean percent breast density of 16% (β = 1.16; 95% CI, 0.92-1.46) in tertile 2 and 24% (β = 1.24; 95% CI, 0.99-1.57) in tertile 3, relative to tertile 1 (Ptrend = 0.07). Similar trends in percent breast density were observed for methylparaben, propylparaben, and butylparaben.

Conclusions: Urinary levels of EDCs were not associated with percent breast density in college-aged women.

Impact: The estimated effect of EDCs on the breast tissue of young women is unclear and warrants larger studies.

Background: Food insecurity is associated with a 40% increase in the prevalence of chronic conditions, including cancer. Stress-evoked inflammation is a hypothesized mechanism driving these associations. This study tested the association between food insecurity and inflammation in cancer survivors.

Methods: Our sample included individuals with a history of lung, breast, prostate, and colorectal cancers from the All of Us Research Program. Food insecurity was measured using validated questions, and inflammatory biomarkers were obtained from electronic health records (EHR). Our primary analysis tested the association between food insecurity and C-reactive protein (CRP; n = 413) using multivariable regression models, controlling for sociodemographics and current cancer treatment.

Results: The primary cohort was 69.8 ± 9.5 years in age, 61.0% female, 89.3% non-Hispanic White, and 9.9% had food insecurity. A higher proportion of racial/ethnic minorities (40.8%) and individuals with lower annual household income (33.3%) and education (29.4%) had food insecurity. The mean CRP was higher among those with food insecurity (14.5 ± 18.5) than among food-secure individuals (10.4 ± 17.8), but it was not significantly associated with CRP in our fully adjusted models.

Conclusions: Lung, breast, prostate, and colorectal cancer survivors had moderate levels of inflammation measured by CRP; however, food insecurity was not associated with CRP in fully adjusted models.

Impact: In this cohort, there was no association between food insecurity and CRP; however, given that food insecurity and inflammation are plausible contributors to chronic disease, future studies should include underrepresented survivors with EHR data and a broader range of cancers.

Background: High-risk human papillomaviruses (HPV-HR) are implicated in more than 99% of cervical/vaginal malignancies. Despite this strong association, current guidelines recommend PET/CT imaging over HPV-HR DNA testing as the standard prognostic tool following definitive therapy. This retrospective, single-institution, proof-of-concept study evaluated HPV-HR DNA testing as a potential alternative to PET/CT imaging for posttreatment surveillance in cervical and vaginal cancers.

Methods: Female patients with cervical or vaginal cancer treated between 2010 and 2023 at our institution were retrospectively analyzed. Eligible patients had complete documentation of pre- and posttreatment PET/CT imaging and HPV-HR DNA testing. Of more than 100 patients identified, only 53 met the inclusion criteria, and both radical hysterectomy and chemoradiation patients were included. Statistical analyses, including sensitivity, specificity, and predictive values, were conducted using Stata, with significance set at 0.05.

Results: Posttreatment HPV-HR DNA testing demonstrated a superior sensitivity (92.31%) and negative predictive value (97.44% NPV) compared with PET/CT imaging (76.92% sensitivity and 92.31% NPV). Although PET/CT imaging maintained higher specificity over HPV-HR DNA testing (100% vs. 95%) and positive predictive value (100% vs. 85.71%), HPV-HR DNA testing offers a more sensitive and cost-effective method for identifying patients requiring further evaluation.

Conclusions: HPV-HR DNA testing is a promising, cost-effective surveillance tool with higher sensitivity and NPV than PET/CT. Its clinical use may reduce PET/CT need, improve safety, and lower costs and require further validation.

Impact: HPV-HR DNA testing offers a cost-effective alternative to PET/CT, reducing costs, unnecessary imaging, and improving accessibility.

Background: Childhood cancer survivors (CCS) are at risk of chronic health conditions due to their cancer and treatment. Cancer survivor programs offer screening services; however, there are disparities in care. Rurality has been understudied; thus, we examined whether rural CCS are at increased risk for non-engagement in survivor care compared with their urban counterparts.

Methods: This retrospective analysis of an institutional CCS cohort evaluated noninitiation of survivor care within 3 years of eligibility and noncontinuation (i.e., no subsequent visit within 18 months of an initial visit). Rurality was defined using rural-urban commuting area codes. Distance from clinic was defined as near (<25 miles) or far (≥25 miles). Outcomes were compared among rural versus urban and urban-near, urban-far, and rural-far CCS using multivariable logistic regressions and cumulative event analysis.

Results: Of 1,515 CCS, 10.7% were rural. Compared with urban CCS, rural CCS had higher odds of survivor care noninitiation [27% vs. 35%; adjusted OR (aOR) = 1.55 (1.06-2.23)] and noncontinuation [23% vs. 32%; aOR = 1.87 (1.17-2.93)]. When including distance, rural-far and urban-far survivors were more likely to not initiate care compared with urban-near survivors [rural-far aOR = 1.95 (1.30-2.90); urban-far aOR = 1.66 (1.28-2.15)], whereas only rural-far CCS were more likely to not continue care [aOR = 2.14 (1.26-3.56)].

Conclusions: A higher proportion of rural CCS did not initiate or continue survivor care compared with urban-near CCS. Rurality and distance to clinic are important in survivor care.

Impact: This analysis reveals that rural CCS are at risk for disparate care. Further studies are needed to determine barriers to care.

Background: Lung cancer screening excludes individuals not considered at an increased risk for lung cancer, as predicted by risk models like the Liverpool Lung Project version 3 (LLPv3). In this study, we sought to validate whether plasma glycosaminoglycan profiles (GAGomes) could predict lung cancer independent of LLPv3 and other prespecified comorbidities.

Methods: In this retrospective cohort-based case-control study, we included patients who were suspected of having lung cancer at baseline and were either diagnosed with lung cancer (cases) or remained cancer-free for 5 years after baseline (controls). Plasma GAGomes were measured at baseline and used to compute a prespecified GAGome score to discriminate lung cancer from controls. We then applied multivariable Bayesian logistic regression to evaluate the likelihood that 7 LLPv3 predictors or 14 comorbidities had an effect on the GAGome score. We tested the independence of the GAGome score from LLPv3-predicted 5-year risk using the likelihood ratio test and assessed whether it improved lung cancer risk prediction in a set equivalent to an LLPv3-predicted 5-year risk of ≥1.51%.

Results: We included 653 lung cancer and 653 controls. The AUC of the GAGome score was 0.63 (95% confidence interval, 0.62-63). None of the LLPv3 predictors or comorbidities were compatible with a significant effect on the score. The GAGome score was independent of LLPv3 (P < 0.001) and improved its sensitivity (72% vs. 69%) and specificity (61% vs. 59%).

Conclusions: Plasma GAGomes identified additional lung cancer cases beyond those predicted by LLPv3 alone.

Impact: GAGomes could improve risk-stratified lung cancer if validated in a screening population.

Background: Human papillomavirus (HPV) assays and self-collection devices for HPV detection have evolved. We aim to compare two self-sampling devices against speculum-based testing for HPV genotype agreement and their accuracy for cervical intraepithelial neoplasia grade 2 (CIN2+) disease. Secondarily, we aim to compare two HPV assays for different HPV genotype detection agreement and their accuracy for CIN2+ disease.

Methods: Women from colposcopy (N = 97) and primary care (N = 96) were block-randomized to two different self-sampling device groups. Self-sampling and speculum-collected pairs of HPV specimens were analyzed with the research assay. A second speculum-collected specimen provided clinical results using the clinical HPV assay. Agreement (prevalence-based κ) and accuracy (sensitivity/specificity ratios) provided the statistical comparison.

Results: The two devices did not differ in their κ agreement scores for overall HPV detection compared with the speculum-collected sample [κ = 0.83 (0.72-0.94) and κ = 0.90 (0.81-0.98), respectively, nonsignificant exact McNemar test results]. The two devices did not differ in accuracy as measured by the relative sensitivity/specificity for overall HPV at the CIN2+ disease threshold [1.0 (0.15-6.77) and 1.19 (0.56-2.54), respectively]. The two assays did not differ in HPV agreement nor assay accuracy for CIN2+ (n = 10).

Conclusions: HPV self-sampling devices robustly detected high-risk HPV types for cervical cancer screening when using the research assay to compare them. Both research and clinical HPV assays provide equivalent HPV detection for specific and aggregated HPV types.

Impact: This study provides a US-based population to show that self-collection for primary HPV testing is accurate for CIN2+ detection with multiple devices using a validated HPV assay.

Background: Evaluating the impact/effectiveness of human papillomavirus (HPV) vaccination generally assumes stability in factors driving transmission, which might not be valid. We aimed to develop, validate, and test a grouping of non-vaccine-preventable HPV (NVP-HPV) types as a molecular indicator associated with sexual behaviors to control for changes in HPV transmission risk.

Methods: We used data from the National Surveys of Sexual Attitudes and Lifestyles (Natsal-2, 1999-2001, N = 1,849; Natsal-3, 2010-2012, N = 2,407) to validate the association of NVP-HPV (26/53/66/70/73) with self-reported sexual behaviors. We calculated NVP-HPV-adjusted HPV16/18 vaccine impact/effectiveness estimates in two real-world scenarios: Natsal-2/Natsal-3 (sexually experienced women in Britain, 18-44 years), and England's HPV surveillance (women, 16-24 years; 2008, N = 3,539; 2010-2020, N = 24,707). Samples (urine/vulvovaginal swabs) were tested for 21 HPV genotypes (6/11/16/18/26/31/33/35/39/45/51/52/53/56/58/59/66/68/70/73/82) using an in-house multiplex PCR and Luminex-based genotyping assay.

Results: NVP-HPV infection was strongly associated with sexual behaviors (e.g., younger age at sexual debut and numbers of partners). In Natsal data, adjusting for NVP-HPV did not change vaccine impact estimates [unadjusted prevalence ratio (PR): 0.50 (0.27-0.95) and adjusted PR: 0.45 (0.25-0.82)]. In the second scenario, adjusting for NVP-HPV did not change the PR for HPV 16/18 when comparing 2020 with 2010 [0.07 (0.03-0.15), unadjusted and adjusted PR]. In both scenarios, the prevalence of NVP-HPV did not change over time.

Conclusions: We have demonstrated proof of concept that NVP-HPV is strongly associated with sexual behaviors. Adjusting for NVP-HPV in two datasets found that the original estimates were robust.

Impact: NVP-HPV might be used to control for changes in HPV transmission risk over time and between groups when evaluating vaccination impact/effectiveness.

Background: Geographic disparities in breast cancer outcomes exist. Few studies have examined community- and health system-level factors associated with care timeliness, an important measure of care quality.

Methods: The Carolina Breast Cancer Study is a population-based cohort of 2,998 women with invasive breast cancer (2008-2013). Using latent class modeling, patients' census tracts of residence were characterized by healthcare accessibility and affordability. Centers for Medicare and Medicaid Services ratings were used to classify hospitals as low- or high-quality. Six timeliness outcomes were assessed: (i) lacking prediagnostic regular care, (ii) being underscreened, (iii) late-stage diagnosis, (iv) delayed treatment initiation, (v) prolonged treatment duration, and (vi) lacking receipt of Oncotype DX genomic testing. Associations of geographic accessibility, healthcare affordability, and hospital-level quality with care timeliness were evaluated with relative frequency differences (RFD) and 95% confidence intervals (CI).

Results: Compared with "high-accessibility, high-affordability" census tracts, patients residing in "low-accessibility, low-affordability" areas were more likely to be underscreened (RFD = 18.7%, CI, 13.0, 24.3), have late-stage diagnosis (RFD = 6.2%, CI, 2.4, 10.1), and experience prolonged treatment (RFD = 6.9%, CI, 1.4, 12.3). "High-accessibility, low-affordability" areas had the highest frequency of treatment delay (RFD = 9.3%, CI, 3.9, 14.7). Initial surgery at a high-quality facility was associated with less delayed treatment (RFD = -3.9%, CI, -7.5, -0.4) and prolonged treatment (RFD = -5.9%, CI, -9.9, -1.9).

Conclusions: Community- and health system-level factors were associated with timely breast cancer care.

Impact: Policy efforts to improve access in communities should consider multiple dimensions of access, including geospatial accessibility and affordability.

Background: Emerging evidence suggests that obesity and lipid profiles may be associated with the development of hematologic malignancies. However, their specific roles in the risk of chronic myeloid leukemia (CML) remain unclear. This study investigated the associations of waist circumference (WC), body mass index (BMI), and high-density lipoprotein cholesterol (HDL-C) levels with the risk of CML in a large population-based cohort.

Methods: A total of 3,879,560 adults from the Korean National Health Insurance Service database were followed from 2009 to 2020. Cox proportional hazards regression was used to estimate adjusted HRs (aHR) and 95% confidence intervals (CI) for incident CML, adjusting for potential confounders.

Results: During a mean follow-up of 10.13 ± 1.24 years, 848 incident CML cases were identified. In women, WC ≥ 95 cm was associated with increased CML risk (aHR, 1.95; 95% CI, 1.19-3.20), as was BMI ≥30 kg/m2 (aHR, 1.97; 95% CI, 1.23-3.16), compared with reference categories. Higher HDL-C levels were inversely associated with CML risk: quartile 3 (aHR, 0.75; 95% CI, 0.62-0.92) and quartile 4 (aHR, 0.81; 95% CI, 0.67-0.99) relative to quartile 1.

Conclusions: Larger WC and higher BMI were associated with increased CML risk, particularly in women, whereas higher HDL-C levels were associated with reduced risk, especially in men.

Impact: These findings indicate that central and general obesity, along with lipid profiles, may be associated with CML risk. Further research is warranted to investigate the potential impact of modifying these factors on CML risk.