Cancer Epidemiology Biomarkers & Prevention最新文献

Background: African American (AA) men are at increased risk of prostate cancer compared with European American (EA) men. Biological mechanisms, including epigenetics, likely contribute to this disparity, but prior studies have been limited by sample size, candidate gene approaches, or lack of epigenome-wide DNA methylation (DNAm) data.

Methods: To improve our understanding of these mechanisms, we compared DNAm features distinguishing tumor and paired histologically benign tissue from 76 AA and 75 EA patients with prostate cancer. We generated genome-wide array-based DNAm data and conducted differential methylation analyses comparing tumor and benign tissues in each ancestry group. We then examined the predictive ability of our identified sites and differential methylation by ancestry group.

Results: We identified 90,747 and 98,929 differentially methylated CpGs in AA and EA, respectively, with 76,400 common to both groups. We identified 6,267 genes with differentially methylated promoters common to both ancestries and 639 and 1,301 genes unique to AA and EA respectively, as well as differentially methylated pathways. Only 10 CpGs were needed to distinguish tumor from benign based on a receiver operating characteristic curve (AUC > 0.9), with differentially methylated CpGs in one ancestry accurately predicting tumor versus benign in the other group. We also identified ancestry-associated CpGs (89 in tumor, 423 in benign).

Conclusions: Methylation features distinguishing tumor and benign were similar for EA and AA men; however, subtle differences were identified.

Impact: Differences in tumor and ancestry-associated CpGs may reveal differential tumor growth strategies, an important area for future disparities research.

In this issue of Cancer Epidemiology, Biomarkers & Prevention, Brantley and colleagues investigated the relationships between estrogen metabolites and postmenopausal breast cancer, using data from a nested case-control study within the Nurses' Health Study. One study aim was to investigate the extent to which estrogen metabolism patterns provided further insights into mechanisms in breast cancer development beyond the role of estradiol. In this editorial, we describe the challenges in interpreting results from observational studies of biomarkers and their role in carcinogenesis due to: (i) a general lack of clarity in the research question, (ii) the limits of current knowledge about the complex underlying causal structure involving interrelated biomarkers, and (iii) the limitations in existing data sources (e.g., biomarkers measured at a single time point). We propose that applying a formal causal inference framework in these studies could be a step forward in improving their rigor, by enabling researchers to be more explicit about the causal effects of interest and the assumptions made, and to advocate for the improvement of future studies. See related article by Brantley et al., p. 375.

Background: Central nervous system (CNS) tumors are the leading cause of cancer-related deaths in children. Although most cases come from low- and middle-income countries (LMIC) where their prognosis is worse, few epidemiologic studies are conducted in these regions.

Methods: We conducted a registry-based cohort study for childhood CNS tumors at Children's Cancer Hospital, Egypt, over 15 years. Unified treatment protocols were implemented. Survival analyses were conducted using the Kaplan-Meier function. Cases were additionally annotated using the International Classification of Childhood Cancer-3 classification.

Results: In total, 5,051 children ≤18 years of age were identified, accounting for 20% of all childhood cancers treated at Children's Cancer Hospital, Egypt. The most common tumor sites were the posterior fossa (36.8%) and brainstem (17.7%). Pathologies were predominantly astrocytic (n = 1,360; 26.9%) and embryonal (n = 1,003; 19.9%) in origin. The 5-year overall survival (OS) and event-free survival for all cases were 64.6% and 51.8%, respectively. More specifically, 1,421 low-grade gliomas were identified, with a 5-year OS of 91.1%. Medulloblastoma (n = 801) recorded a 5-year OS of 66%. The entity with the worst prognosis was diffuse intrinsic pontine glioma (n = 633), with a 5-year OS of 3.2%.

Conclusions: We report on a large number of childhood CNS tumors from an LMIC. This study underscores the need to understand the burden of childhood brain tumors and its outcomes in resource-constrained settings.

Impact: This study reports on the epidemiology and clinical outcomes of 5,000+ children with CNS tumors from a specialized LMIC center. Despite the lack of many sophisticated and advanced facilities, LMICs can improve the clinical end-results with experience and augmented efforts.

Background: Estradiol and estrone are well-established risk factors for postmenopausal breast cancer. Experimental evidence suggests that specific estrogen metabolites, produced via irreversible hydroxylation of estrone and estradiol at position 2 or 16, may independently influence carcinogenesis.

Methods: We performed a nested case-control study of breast cancer (328 breast cancer cases; 639 controls) among postmenopausal women within the Nurses' Health Study to examine the role of estrogens and estrogen metabolites (jointly referred to as EM). Plasma concentrations of each EM (unconjugated + conjugated forms) were measured by LC-MS/MS. Multivariable conditional logistic regression, adjusting for breast cancer risk factors, estimated relative risks (RR) and 95% confidence intervals of breast cancer across quintiles of individual EM, EM pathways, and pathway ratios. Associations by estrogen receptor (ER) and progesterone receptor (PR) status were analyzed by unconditional logistic regression.

Results: Estradiol and estrone were strongly associated with increased breast cancer risk [estradiol: RRQ5 vs. Q1 (95% confidence interval) = 2.64 (1.64-4.26); estrone: 2.78 (1.74-4.45); both P-trends <0.001]. The 2-hydroxylation pathway was strongly associated with risk [RRQ5 vs. Q1 = 3.09 (1.81-5.27); P-trend <0.001] and remained so after adjusting for unconjugated estradiol [RRQ5 vs. Q1 = 2.23 (1.25-3.96); P-trend = 0.01]. Although the 16-hydroxylation pathway was modestly associated with risk [RRQ5 vs. Q1 = 1.62 (1.03-2.54); P-trend = 0.01], the association was attenuated after unconjugated estradiol adjustment [RRQ5 vs. Q1 = 1.24 (0.77-1.99); P-trend = 0.19]. Similar positive associations with the 2-pathway and 16-pathway were observed for ER+/PR+ and ER-/PR- tumors.

Conclusions: In this cohort of postmenopausal women, 2-hydroxylation of estrone and estradiol was associated with increased breast cancer risk, independent of unconjugated estradiol.

Impact: These results highlight the need to revisit the role of estrogen metabolism in breast cancer etiology and prevention. See related In the Spotlight, p. 367.

Background: The relationship between omega-3 polyunsaturated fatty acid (n-3 PUFA) intake and colorectal cancer risk is unclear. Blood n-3 PUFA concentration is a biomarker of dietary n-3 PUFA intake. We examined the relationship between plasma n-3 PUFA concentrations and colorectal cancer risk in UK Biobank (UKBB) participants.

Methods: We analyzed the relationship between tertiles (T) of plasma total n-3 PUFAs and n-3 PUFA docosahexaenoic acid (DHA) levels, and overall colorectal cancer (also stratified by tumor location and sex) risk. Cox proportional hazards regression models were adjusted for clinical covariates. Nonlinearity was tested by restricted cubic splines.

Results: There were 2,602 incident colorectal cancer cases in 234,598 UKBB participants with baseline plasma fatty acid data (mean follow-up 13.4 years). There was an inverse association between the plasma total n-3 PUFA level [T2 HR = 0.88 (95% confidence interval, 0.80-0.97) compared with the T1 reference; T3 = 0.91 (0.83-1.00)], as well as the plasma DHA concentration [T2 = 0.89 (0.80-0.98); T3 = 0.91 (0.82-1.00)], and colorectal cancer risk. The relationship was nonlinear [P for nonlinearity = 0.14 (total n-3 PUFAs) and 0.008 (DHA)], with a plateau effect at the highest n-3 PUFA concentrations. The relationship was more pronounced for proximal colon cancer [T2 = 0.82 (0.69-0.97); T3 = 0.76 (0.64-0.90) for DHA] and was evident for males [T2 = 0.84 (0.74-0.95); T3 = 0.89 (0.78-1.00)], but not for females.

Conclusions: Higher plasma n-3 PUFAs are associated with reduced colorectal cancer risk in the UKBB.

Impact: Nonlinearity, as well as tumor site and sex specificities, of the inverse relationship between plasma n-3 PUFA levels and colorectal cancer risk, if confirmed in other diverse populations, has significant implications for nutritional prevention guidelines.

Background: The reports have stated that the timeliness of lung cancer care varies significantly across different regions. According to the Victorian Lung Cancer Registry report, the timeliness of lung cancer care in Victoria has changed over time. Therefore, we aimed to quantify the extent of these spatial inequalities over time and to identify area-level determinants contributing to these changes.

Methods: The study analyzed lung cancer cases reported to the Victorian Lung Cancer Registry between 2011 and 2022. Bayesian spatiotemporal conditional autoregressive models were fitted, incorporating spatial random effects, temporal random effects, and spatiotemporal interactions. The best performing model was selected using the deviance information criterion. For the final best fit model, the adjusted RRs and their 95% credible intervals were reported.

Results: More than half (51.24%) of patients with lung cancer experienced treatment delays, whereas approximately one third (30.98%) encountered diagnostic delays. Moderate spatiotemporal variations were observed in both delayed diagnosis and treatment. In the final best fit model for treatment delay, an increase in the percentage of smokers was significantly associated with a higher risk of treatment delay (RR = 2.13; 95% credible interval, 1.13-4.20).

Conclusions: Identifying high-risk areas provides useful information for policymakers, helping in the reduction of delays in lung cancer diagnosis and treatment.

Impact: This study has revealed spatiotemporal inequalities in diagnostic and treatment delays, providing valuable insights for identifying areas that should be prioritized to ensure timely care for lung cancer.

Background: Screening colonoscopy harm data are limited for adults ages 76 to 85 years.

Methods: We conducted a retrospective cohort study of screening colonoscopies versus fecal immunochemical tests (FIT) and general population matched comparators ages 76 to 85 years within three integrated healthcare systems (2010-2019). The primary outcome was death or overnight hospitalization within 30 days. A secondary outcome also included nine harm diagnoses. Adjusted risk estimates and risk differences (RD) were obtained using Poisson regression. Narrow analyses excluded outcomes after the next lower endoscopy or colorectal procedure, whereas broad analyses included them.

Results: Patients undergoing screening colonoscopy (N = 4,435) had a higher 10-day cumulative incidence of gastrointestinal bleeding {0.18% [95% confidence interval (CI), 0.09%-0.35%]} and perforation [0.09% (95% CI, 0.03%-0.23%)] than those with FIT (N = 17,740) and the general population (N = 44,350) in the narrow analysis. Screening colonoscopy patients had a 1.04% (95% CI, 0.74%-1.34%) risk of death or hospitalization within 30 days in the narrow analysis, similar to those with FIT [RD = 0% (95% CI, -0.36% to 0.35%)] and the general population [RD = -0.07% (95% CI, -0.39% to 0.25%)]. In the broad analysis, risk following colonoscopy was 2.30% (95% CI, 1.85%-2.75%) with RD = 1.13% (95% CI, 0.67%-1.60%) versus general population [ages 76-80 years: RD = 0.93% (95% CI, 0.45%-1.41%) and ages 81-85 years: RD = 2.14% (95% CI, 0.74%-3.54%)]. Secondary outcomes followed a similar pattern by age.

Conclusions: At ages 76 to 85 years, screening colonoscopies including downstream procedures are associated with an increased short-term risk of death or hospitalization.

Impact: Harm data can be combined with benefit data to guide screening colonoscopy decisions among older adults.

Background: The growing population of male adolescent and young adult (AYA, ages 15-40 years) cancer survivors has heightened interest in their reproductive health. However, studies have reported conflicting findings on the potential risks of cancer and its treatments on birth and obstetric outcomes.

Methods: We used encrypted identification numbers for both fathers and mothers to link three nationwide Taiwan datasets from 2004 to 2019, identifying 3,785 births with a paternal history of AYA cancer. For comparison, we included 37,850 matched fathers without a cancer history, matched by paternal age and infant birth year. We used multivariable logistic regression analysis to identify independent associations between adverse birth outcomes (e.g., preterm labor, low birthweight, and congenital malformations) and obstetric outcomes (e.g., fetal growth restriction, threatened labor, and threatened abortion) and being born to male AYA cancer survivors.

Results: The offspring of male AYA cancer survivors did not exhibit a significantly increased risk of adverse birth (OR = 1.0; 95% confidence interval, 0.9-1.1) or obstetric (OR = 1.1; 95% confidence interval, 1.0-1.1) outcomes compared with offspring born to cancer-free matched fathers. Furthermore, the risk of preterm labor, low birthweight, congenital malformations, fetal growth restriction, and threatened labor or miscarriage was comparable between groups.

Conclusions: Paternal cancer history during adolescence or young adulthood does not seem to increase the risk of adverse birth or obstetric outcomes in offspring.

Impact: This study reassures the reproductive health of this population, providing valuable insights for oncology and reproductive medicine, potentially influencing patient counseling and guidelines.

Background: Hepatocellular carcinoma (HCC) disproportionately affects racial/ethnic minorities. We evaluated the impact of income and geography on racial/ethnic disparities across the HCC care cascade in the United States.

Methods: Using NCI registry data spanning 2000 to 2020, adults with HCC were evaluated to determine race/ethnicity-specific differences in tumor stage at diagnosis, delays and gaps in treatment, and survival. Adjusted regression models evaluated predictors of HCC outcomes.

Results: Among 112,389 adults with HCC, cohort characteristics were as follows: 49.8% non-Hispanic White (NHW), 12.0% African American(AA), 20.5% Hispanic, 16.5% Asian/Pacific Islander, and 1.1% American Indian/Alaska Native. Compared with NHW patients, AA patients had lower odds of localized-stage HCC at diagnosis [adjusted odds ratio (aOR), 0.84], lower odds of HCC treatment receipt (aOR, 0.77), greater odds of treatment delays (aOR, 1.12), and significantly greater risk of death [adjusted hazards ratio (aHR), 1.10]. Compared with NHW patients from large metro areas, AA patients from large metro areas had 8% higher mortality risk (aHR, 1.08), whereas AA patients from small-medium metro areas had 17% higher mortality risk (aHR, 1.17; all P < 0.05).

Conclusions: Among a population-based cohort of US adults with HCC, significant race/ethnicity-specific disparities across the HCC care continuum were observed. Lower household income and more rural geography among racial/ethnic minorities are also associated with disparities in HCC outcomes, particularly among AA patients.

Impact: Our study shows that lower income and less urban/more rural geography among racial/ethnic minorities are also associated with disparities in HCC outcomes, particularly among AA patients with HCC. This contextualizes the complex relationship between sociodemographic factors and HCC outcomes through an intersectional lens.