Cancer Epidemiology Biomarkers & Prevention最新文献

Background: Despite the promise of mail-based human papillomavirus (HPV) self-collection programs for increasing cervical cancer screening, few have been evaluated in the United States. We report the results of a mail-based HPV self-collection program for underscreened women living in Appalachia.

Methods: We conducted a group randomized trial during 2021-2022 in the Appalachian regions of Kentucky, Ohio, Virginia, and West Virgnia. Participants were women ages 30-64 who were underscreened for cervical cancer and from a participating health system. Participants in the intervention group (n=464) were mailed an HPV self-collection kit followed by telephone-based patient navigation (if needed), and participants in the usual care group (n=338) were mailed a reminder letter to get a clinic-based cervical cancer screening test. Generalized linear mixed models compared cervical cancer screening between study groups.

Results: Overall, 14.9% of participants in the intervention group and 5.0% of participants in the usual care group were screened for cervical cancer. The mail-based HPV self-collection intervention increased cervical cancer screening compared to the usual care group (OR=3.30, 95% CI: 1.90-5.72, p=0.005). One or more high-risk HPV types were detected in 10.5% of the returned HPV self-collection kits. Among participants in the intervention group who patient navigators attempted to contact, 44.2% were successfully reached.

Conclusions: HPV self-collection increased cervical cancer screening, and future efforts are needed to determine how to optimize such programs, including the delivery of patient navigation services.

Impact: Mail-based HPV self-collection programs are a viable strategy for increasing cervical cancer screening among underscreened women living in Appalachia.

Background: Ferritin, an iron storage protein and acute phase reactant, has been implicated in various aspects of human health and disease, including cancer. Previous studies have identified elevated serum ferritin (SF) levels in several cancer types, but a comprehensive examination across different malignancies remains lacking. This study aims to fill this gap by utilizing anonymized data from Maccabi Health Services (MHS), one of Israel's largest health organizations, to explore the association between elevated SF levels and the diagnosis of different malignancies.

Methods: An extensive dataset from MHS, comprising 2.7 million members, including 1.3 million individuals who underwent SF level testing, was analyzed. Odds Ratios (OR) and 95% confidence intervals (CI) were calculated to assess the association between high SF levels and cancer diagnosis. Subgroup analysis was conducted to investigate variations across different malignancies.

Results: The analysis revealed a significant association between elevated SF levels and cancer diagnosis among MHS members, with an OR of 1.9 (95% CI 1.71-2.15). Sub- group analysis unveiled differences in the association across malignancy types, with hematological, hepatobiliary and respiratory malignancies more strongly associated with high SF levels.

Conclusions: This study provides further support for the link between elevated SF levels and malignancy, leveraging a vast dataset from MHS, underscoring potential utilities of elevated SF levels as a potential indicator for cancer with a variable role among different malignancy types.

Impact: The identification of elevated SF levels as a potential indicator for underlying malignancy for seemingly-healthy individuals.

Background: Invasive lobular carcinoma (ILC) exhibits differences in molecular and biological characteristics compared to invasive ductal carcinoma (IDC). We aim to compare breast cancer-specific survival (BCSS) between patients with ILC and IDC.

Methods: We used data from the Surveillance, Epidemiology, and End Results database (1992-2020). Logistic regression analyses were conducted to identify factors associated with treatment modalities. We examined BCSS at different time points using a cox regression model with time-dependent coefficient.

Results: 343,397 patients with IDC and 39,859 patients with ILC were included. Patients with ILC had more advanced stage disease (stage II, 35% vs. 34%; stage III, 16% vs.11%), and higher rate of hormone receptor-positive disease (97% vs. 81%). Compared to patients with IDC, patients with ILC had better BCSS in the first five years (Hazard ratio [HR]=0.71, p <0.001), but worse BCSS in later years (HR=1.30, p<0.001 in year 6-10; HR=1.75, p<0.001 in year 11-15; HR=2.17, p<0.001 in year 16-20).

Conclusions: Patients with ILC survive better in early years but worse in later years compared to patients with IDC. Future studies are required to identify patients with ILC who are at risk of late recurrence or mortality.

Impact: The results of this study add to the currently conflicting literature of survival of ILC and demonstrate the importance of evaluating novel therapeutic approaches and extended therapy for patients with ILC.

Background: Improvements in cancer control have led to a drastic increase in cancer survivors who may be at an elevated risk of developing subsequent primary cancers (SPC). In this study, we assessed the risk and patterns of SPC development among 196,858 adult cancer survivors in Alberta, Canada.

Methods: We used data from the Alberta Cancer Registry to identify all first primary cancers occurring between 2004 and 2020. A SPC was considered as the next primary cancer occurring in a different site. We estimated standardized incidence ratios (SIR) for SPC development as the observed number of SPC (O) divided by the expected number of SPC (E), where E is a weighted-sum of the population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up.

Results: The risk of developing a SPC up to fifteen years after an initial cancer was 16.2% for males and 12.2% for females. Overall, both males (SIR=1.50) and females (SIR=1.58) had an increased risk of a SPC. There were significant increases in SPC risk for nearly all age groups, with a greater than 5-fold increase for survivors diagnosed between ages 18-39. Screen-detectable cancers including colorectal, lung, cervix, and breast accounted for 46% and 27% of SPCs among females and males.

Conclusions: Cancer survivors of nearly every initial site had substantially increased risk of a SPC, compared to the cancer risk in the general population.

Impact: Screen-detectable cancers were common SPC sites and highlights the need to investigate optimal strategies for screening the growing population of cancer survivors.

Background: HPV vaccination coverage is characterized by geographic disparities in the US, with national studies finding lower coverage in rural versus nonrural areas. To direct quality improvement efforts in North Carolina, we sought to understand how different rurality measures characterize these disparities.

Methods: We used separate negative binomial regression models to test associations between 5 dichotomized county-level rurality measures and HPV vaccination coverage (≥1 dose) among North Carolina adolescents, ages 11-12 (n=326,345). Rurality measures were derived from: Office of Management and Budget's Metropolitan Statistical Areas, Rural-Urban Continuum Codes, Index of Relative Rurality, US Census Bureau classifications, and North Carolina Rural Center classifications. Models controlled for Social Vulnerability Index (SVI) percentile and rate of pediatricians per county. Vaccination data came from the North Carolina Immunization Registry.

Results: HPV vaccination coverage was 29% across North Carolina's 100 counties (range: 13%, 46%). Agreement between rurality measures ranged from 54% to 93% of counties. In adjusted analyses, none of the 5 rurality measures correlated with HPV vaccination coverage, but higher SVI and higher rate of pediatricians were positively associated with coverage (p< 0.01). Exploratory moderation analyses suggested regional variation in the relationship between rurality and coverage, with a positive association in one region, a negative association in one region, and no association in four regions.

Conclusions: County-level rurality measures did not identify disparities in HPV vaccination coverage in North Carolina.

Impact: Measures related to social vulnerability and access to pediatricians may be better suited for understanding and addressing the state's substantial county-level vaccination disparities.

Background: Annual mammography screening declined year-on-year during the COVID-19 pandemic through 2021. This study examined changes in 2022 compared to 2018 in the national prevalence of self-reported up-to-date mammography.

Methods: Using 2018-2022 data from the Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS), we assess relative changes defined as annual prevalence ratios (aPR) in the SR receipt of past-year and up-to-date (UTD) breast cancer screening (bi-annual mammography in women ages 50-74 years) during the third year of the COVID-19 pandemic overall and by sociodemographic characteristics.

Results: UTD BC screening declined for the first time since 2018 (2018 compared to 2022, from 78.7% to 76.6%; aPR, 0.97; 95% CI, 0.96-0.98), despite a small increase in past-year breast cancer screening from 2020 and 2022 (57.9% to 59.6%; aPR, 1.03; 95% CI, 1.01-1.05). This translated to 747,791 fewer women reporting UTD with recommended BC screening in 2022 vs. 2018. UTD BC screening declines between 2018-2022 were largest for American Indian/Alaska Native women (74.8% to 62.2%; aPR, 0.83; 95% CI, 0.74-0.93), women with less formal educational attainment (< high school: 73.1% to 65.5%; aPR, 0.9; 95% CI, 0.85-0.95), and women without a usual source of care (48% to 42.9%; aPR, 0.85; 95% CI, 0.78-0.92).

Conclusions: Previously noted pandemic-related declines in past-year BC screening now reflect in women reporting being UTD, with the largest declines in AI/AN and lower SES women.

Impact: Future studies should monitor screening prevalence in relation to BC diagnostic stage, overall and by sociodemographic groups.

Background: Breast cancer (BC) incidence is increasing in women under age 40 years, underscoring the need for research on BC risk factors for younger women.

Methods: We used data from an international family cohort (n=26,348) to examine whether recreational physical activity (RPA) during adolescence and early adulthood are associated with BC risk before age 40. The cohort includes 2,502 women diagnosed with BC before age 40, including 2,408 diagnosed before study enrollment (68% within 5 years of enrollment). Women reported their average hours-per-week of moderate and strenuous RPA during adolescence (12-17 years) and early adulthood (25-34 years), which were converted to total age-adjusted metabolic equivalents-per-week and categorized into quartiles. We conducted attained age analyses until age 40 (follow-up time began at age 18) using Cox proportional hazards regression models adjusted for study center, race and ethnicity, and education.

Results: Being in the highest versus lowest quartile of RPA during adolescence and early adulthood were respectively associated with 12% [HR (95% CI): 0.88 (0.78, 0.98)] and 16% [HR (95% CI): 0.84 (0.74, 0.95) lower BC risks before age 40. Being in the highest quartile of RPA during both adolescence and early adulthood (Pearson correlation=0.52) versus neither timepoint was associated with a 22% lower risk [HR (95% CI): 0.78 (0.68, 0.89)].

Conclusions: Findings suggest that RPA during adolescence and early adulthood may lower BC risk before age 40.

Impact: Policies promoting physical activity during adolescence and early adulthood may be important for reducing the growing burden of breast cancer in younger women.

Intrathoracic cancers, including lung cancer, mesothelioma, and thymoma, present diagnostic challenges in primary care. Biomarkers could resolve some challenges. We synthesized evidence on biomarkers performance for intrathoracic cancer detection in low-prevalence settings. A search in EMBASE and MEDLINE included studies that recruited participants with suspected intrathoracic cancer and reported on at least one diagnostic measure for a validated, non-invasive biomarker. Studies were excluded if participants were recruited based on a pre-established diagnosis. Fifty-two studies were included, reporting on 108 individual biomarkers and panels. CEA, CYFRA 21.1, and VEGF were evaluated for lung cancer and mesothelioma. For lung cancer, CEA and CYFRA 21.1 were most studied, with AUCs of 0.48-0.90 and 0.48-0.83, respectively. Pro-GRP and NSE had the highest NPVs (98.2%, 96.9%), while Early-CDT and MSC panels showed NPVs of 99.3% and 99.0% in smokers. For mesothelioma, Fibrillin-3 and mesothelin plus osteopontin had AUCs of 0.93 and 0.91, respectively. Thymoma panels (Binding AcHR + StrAb) and (Binding AcHR + Modulating AcHR + StrAb) had 100% NPVs in myasthenia gravis patients. The review highlights the performance of some biomarkers. However, few were evaluated in low-prevalence settings. Further evaluation is necessary before implementing these biomarkers for intrathoracic cancers in primary care.

Background: Biomarker analyses are an integral part of cancer research. Despite the intense efforts to identify and characterize biomarkers in cancer patients, little is known regarding the natural variation of biomarkers in healthy populations. Here we conducted a clinical study to evaluate the natural variability of biomarkers over time in healthy participants.

Methods: The angiome multiplex array, a panel of 25 circulating protein biomarkers, was assessed in 28 healthy participants across 8 timepoints over the span of 60 days. We utilized the intraclass correlation coefficient (ICC) to quantify the reliability of the biomarkers. Adjusted ICC values were calculated under the framework of a linear mixed-effects model, taking into consideration age, sex, body mass index (BMI), fasting status, and sampling factors.

Results: ICC was calculated to determine the reliability of each biomarker. HGF was the most stable marker (ICC=0.973), while PDGF-BB was the most variable marker (ICC=0.167). In total, ICC analyses revealed that 22 out of 25 measured biomarkers display good (≥0.4) to excellent (>0.75) ICC values. Three markers (PDGF-BB, TGF-1, PDGF-AA) had ICC values <0.4. Greater age was associated with higher IL-6 (p=0.0114). Higher BMI was associated with higher levels of IL-6 (p=0.0003) and VEGF-R3 (p=0.0045).

Conclusions: Of the 25 protein biomarkers measured over this short time period, 22 markers were found to have good or excellent ICC values, providing additional validation for this biomarker assay.

Impact: This data further supports the validation of the angiome biomarker assay and its application as an integrated biomarker in clinical trial testing.

Background: The current e-cigarette market has been rapidly evolving with an increase in the share of high nicotine concentration vaping products. This study examined urinary biomarkers of exposure (BOEs) by nicotine concentration level among exclusive e-cigarette users.

Methods: Data were drawn from Wave 5 (December 2018-November 2019) of the Population Assessment of Tobacco and Health (PATH) Study. Between-subject differences in BOEs of nicotine, metal, tobacco-specific nitrosamine (TSNA), and volatile organic compounds (VOC) were examined across e-cigarettes containing nicotine or not (yes [n=300] vs. no [n=31] vs. non-tobacco use [n=3021]) and different nicotine concentration levels (0.1-1.7%, 1.8-4.9%, and 5.0%+).

Results: Among 3353 participants, exclusive e-cigarette users exhibited higher mean concentrations of nicotine metabolites than non-tobacco users. Nicotine e-cigarette users had higher concentrations of TNE2 (mean [95% CI]=21.8 [15.2-31.2] vs. 0.2 [0.1-0.6] nmol/mg creatinine, p<.0001) and cotinine (1418.2 [998.0-2015.4] vs. 12.2 [0.1-0.6], p<.0001) ng/mg creatinine, p<.0001) than non-nicotine e-cigarette users. Users of e-cigarette products with nicotine levels of 1.8-4.9% had higher TNE2 and cotinine levels than those using 0.1-1.7%, though differences were insignificant after adjusting for covariates. As compared to non-tobacco users, nicotine vapers had higher concentrations of lead (adjusted p=0.01).

Conclusions: Nicotine containing e-cigarette users exhibited elevated levels of nicotine metabolites than non-nicotine containing vapers and non-tobacco users. Future research needs to investigate health effects of e-cigarette use across different nicotine levels Impact: Regulating the nicotine content in e-cigarettes could be crucial in managing nicotine exposure and potentially mitigating associated health risks.