Cancer Epidemiology Biomarkers & Prevention最新文献

Background Waist circumference (WC) and its allometric counterpart, "a body shape index" (ABSI), are risk factors for colorectal cancer (CRC); however, it is uncertain whether associations with these body measurements are limited to specific molecular subtypes of the disease. Methods Data from 2,772 CRC cases and 3,521 controls were pooled from four cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium. Four molecular markers (BRAF mutation, KRAS mutation, CpG island methylator phenotype, and microsatellite instability) were analysed individually and in combination (Jass-types). Multivariable logistic and multinomial logistic models were used to assess the associations of WC and ABSI with overall CRC risk and in case-only analyses evaluating heterogeneity by molecular subtype, respectively. Results Higher WC (ORper 5cm=1.06, 95%CI:1.04-1.09) and ABSI (ORper 1-SD=1.07, 95%CI:1.00-1.14) were associated with elevated CRC risk. There was no evidence of heterogeneity between the molecular subtypes. No difference was observed regarding the influence of WC and ABSI on the four major molecular markers in proximal colon, distal colon, and rectal cancer, as well as in early and later onset CRC. Associations did not differ in the Jass-type analysis. Conclusions Higher WC and ABSI were associated with elevated CRC risk; however, they do not differentially influence all four major molecular mutations involved in colorectal carcinogenesis but underscore the importance of maintaining a healthy body weight in CRC prevention. Impact The proposed results have potential utility in colorectal cancer prevention.

Background: Current evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer (CRC). However, the mediating role of the circulating metabolome in this relationship remains unclear.

Methods: Targeted metabolomics data from 6,055 participants in the EPIC cohort were used to identify metabolites associated with PA and derive a metabolomic signature of PA levels. PA levels were estimated using the validated Cambridge PA index based on baseline questionnaires. Mediation analyses were conducted in a nested case-control study (1,585 cases, 1,585 controls) to examine whether individual metabolites and the metabolomic signature mediated the PA-CRC association.

Results: PA was inversely associated with CRC risk (odds ratio [OR] per category change: 0.90, 95% confidence intervals [CI]: 0.83, 0.97; p-value = 0.009). PA levels were associated with 24 circulating metabolites after false discovery rate correction (FDR), with the strongest associations observed for phosphatidylcholine acyl-alkyl (PC ae) C34:3 (FDR-adjusted p-value = 1.18 × 10⁻¹⁰) and lysophosphatidylcholine acyl (lysoPC a) C18:2 (FDR-adjusted p-value = 1.35 × 10⁻⁶). PC ae C34:3 partially mediated the PA-CRC association (natural indirect effect: 0.991, 95% CI: 0.982, 0.999; p-value = 0.04), explaining 7.4% of the association. No mediation effects were observed for the remaining metabolites or the overall PA metabolite signature.

Conclusions: PC ae C34:3 mediates part of the PA-CRC inverse association, but further studies with improved PA measures and extended metabolomic panels are needed.

Impact: These findings provide insights into PA-related biological mechanisms influencing CRC risk and suggest potential targets for cancer prevention interventions.

Background: Worldwide trends support the increasing contribution of hepatic steatosis on the incidence of hepatocellular carcinoma (HCC). This study investigates if similar changes are seen in Hawaii, where the incidence of HCC is higher than most of the United States. Methods; This is a retrospective study of 1651 patients diagnosed with HCC (1991-2023) that includes 60-70% of Hawaii's HCC cases. We evaluated changes in patient demographics, risk factors, and disease etiology over the three decades.

Results: From 1991-2023, there were significant increases in the proportion of HCC cases attributable to metabolic-associated steatotic liver disease(MASLD), coinciding with a rise in the prevalence of metabolic risk factors including obesity, diabetes, hyperlipidemia, and hypertension. Cases with a history of smoking also increased through 2020. Conversely, HCC cases presenting with cirrhosis alone decreased. HCV-associated cases increased through 2015 and then tapered, while HBV-associated cases decreased through 2020. There was no significant change in the proportion of alcohol-associated cases.

Conclusions: While HBV continues to be a major contributor to HCC in Hawaii, HCV-related HCC cases have tapered, while metabolic risk factors for HCC and cases attributable to MASLD have increased over time, parallelling overall trends observed in the United States. Efforts are needed to manage these metabolic factors to address the burden of HCC. Impact; Although Hawaii continues to have a large burden of viral hepatitis related HCC, metabolic factors and MASLD have affected the pathogenesis of liver cancer in Hawaii over the past the past 3 decades.

Background: Esophageal squamous cell carcinoma (ESCC) exhibits a long latency period and has a significant geographical disparity in incidence, which underscores the need for models predicting the long-term absolute risk adaptable to regional disease burden.

Methods: 31,883 participants in a large-scale population-based screening trial (Hua County, China) were enrolled to develop the model. Severe dysplasia and above (SDA) identified at screening or follow-up were defined as the outcome. We calculated the absolute risk in three steps: 1) constructing a relative risk model using logistic regression, 2) calculating the age-specific baseline hazard, and 3) adjusting for the competing risk of all-cause death excluding ESCC. Flexible incidence rate parameters were integrated into the model to ensure its relevance across diverse regions worldwide.

Results: A total of 295 SDAs were detected. The relative risk model consisted of old age, male gender, irregular meal pattern, preference for hot or hard food, BMI of less than 22 kg/m2, and ESCC family history. The area under the receiver operating characteristic curve was 0.753 (95% CI: 0.749-0.757). The averaged 5-year and 10-year absolute risk were 0.53% and 1.30% among participants. Based on our model, we developed an online calculator incorporated flexible incidence rate parameters, demonstrating ideal risk stratification tailored to regions with varying disease burdens (https://pkugenetics.shinyapps.io/escc_risk_prediction/).

Conclusions: We developed an absolute risk model to predict individualized long-term risk of ESCC, accounting for local disease burden.

Impact: This model has the potential to mitigate the global burden of ESCC by enabling targeted screening and personalized prevention strategies.

Background: Oropharyngeal cancer (OPC) incidence is rising globally, predominantly in high-income countries due to human papillomavirus (HPV) infection. However, further data on OPC incidence in Brazil is needed. The aim of this study was to estimate the incidence, trends, and predictions of OPC in Brazilian population-based cancer registries (PBCRs) by period, sex, and topography.

Methods: Data on OPC were collected from PBCRs (1988-2020). Age-standardized rates were calculated from 2000 onwards, using the 2010 Brazilian census and world standard population. Annual average percent change was analyzed using the Joinpoint Regression Model. Predictions up to 2034 were made using the Nordpred program and the age-period-cohort model.

Results: A total of 17,980 OPC cases were recorded across 30 PBCRs (1988-2020). Most cases involved males (81.58%) aged 55-59 years (17.06%). The oropharynx NOS (not otherwise specified) (40.58%), base of the tongue (24.98%), and tonsils (22.52%) were the sites most affected. The highest incidence rates were found in the Southeastern and Southern regions (3.1 to 9.4/100,000). Incidence trends increased for 10 PBCR regions in males and six regions in females. Predictions up until 2034 indicate decreasing trends for females and increasing trends for males in the North and South of Brazil.

Conclusions: The incidence of OPC in Brazil differs among regions, with higher rates observed in the South and Southeast. The prevalence of the HPV-attributable fraction for OPC is unknown.

Impact: Analysis of OPC incidence rates and regional trends aims to better understand the epidemiology of this malignancy in the Brazilian population.

Background: Kentucky is within the top five leading states for breast mortality nationwide. This study investigates the association between neighborhood socioeconomic disadvantage and breast cancer outcomes, including surgical treatment, radiation therapy, chemotherapy, and survival, and how associations vary by race and ethnicity in Kentucky.

Methods: We conducted a retrospective cohort analysis using data from the Kentucky Cancer Registry (KCR) for breast cancer patients diagnosed between 2010 and 2017, with follow-up through December 31, 2022. We linked KCR data with census tract data to examine the relationship of Area Deprivation Index (ADI) on breast cancer outcomes. Logistic regression and Cox Proportional Hazards models analyzed binary outcomes and time-to-event data, respectively.

Results: Women in the most disadvantaged (ADI 4th quartile) neighborhoods were more likely to be diagnosed at later stages (OR: 1.26, 95% CI: 1.12-1.41) and 34% more likely to die from breast cancer (HR: 1.34, 95% CI: 1.14-1.57) after adjusting for age, race, tobacco use, tobacco pack years, marital status, insurance status, family history, stage at diagnosis, breast cancer subtype, and residence in Appalachia when compared to women living in the least disadvantaged neighborhoods (ADI 1st quartile).

Conclusions: Women in disadvantaged neighborhoods had significantly higher odds of late-stage diagnosis and breast cancer death, regardless of race, indicating that neighborhood factors contribute to breast cancer disparities.

Impact: Socioeconomic and neighborhood factors may contribute to breast cancer outcomes, suggesting the necessity for targeted interventions. Future research should explore the effectiveness of such interventions and investigate additional social determinants contributing to disparities.

Background: While community engagement has had a substantial presence in public health research, community input to inform geospatial and health analyses remains underutilized and novel. This manuscript reports on community engagement activities to solicit stakeholder perspectives on the role of neighborhood conditions in health and cancer. We discuss how this community input refined a priori conceptual model to be tested in the larger Families, Friends, and Neighborhoods (FFAN) Study.

Materials and methods: We conducted semi-structured virtual interviews with 82 stakeholders (e.g., community and faith leaders, educators, healthcare workers) across four states (Maryland, Connecticut, Alabama, Missouri). Participants discussed how where a person lives can impact their health and cancer risk. We subsequently convened a virtual group discussion with 17 randomly selected interviewees. Our study team individually reviewed discussion notes, which were synthesized into a consensus document.

Results: In addition to constructs from the original conceptual model, participants identified neighborhood-level factors not in the original model, including K-12 education quality, local property investment, homelessness, public transportation infrastructure, proximity to healthcare facilities, environmental toxin exposures, access to healthy foods, and cost of living. These factors will be incorporated into the FFAN study analytic models.

Conclusions: Though geospatial analyses in health research has not traditionally employed community engagement techniques, this study illustrates the value of informing multi-level analytic models with the lived experiences of those negatively impacted by neighborhood conditions that underlie the risk, prevention, and screening behaviors driving cancer incidence and mortality.

Impact: Future social epidemiology research can be enriched through community engagement.

Background: Skin-cancers are the most common cancers in Caucasians, and their incidence is rising. Although metabolic and anthropometric markers play a role in cancer development, the relationship of metabolic and anthropometric changes with skin-cancer remains unclear. This study aimed to examine possible associations between these changes and the risk of skin-cancer.

Methods: Participants without prior skin-cancer history from the Northern-Netherlands representative of the general population were included. Histopathology data were obtained from the Dutch Nationwide Pathology-Database. Adjusted-Cox-regression analyzed associations between metabolic changes and time to pathology-confirmed skin-cancer incidence over a 7-year follow-up, assessing overall skin-cancer risk and subtypes, including melanoma and non-melanoma skin-cancer.

Results: Out of 97,106 participants, 4,195 (4.3%) developed skin-cancer. Body-mass-index (BMI) decrease and increase were both associated with lower skin-cancer risk: adjusted-hazard-ratios(aHR) of 0.88(0.80-0.98) and 0.78(0.72-0.86), respectively. Triglyceride and waist-to-hip ratio (WHR)decreases were also associated with lower risk: aHR: 0.89(0.80-0.98) and 0.89(0.83-0.98), respectively. Increase in HbA1c was associated with higher risk in individuals under 45 years at baseline: aHR: 1.21(1.01-1.45). Subtype-analysis showed an increase in BMI was associated with lower melanoma risk: aHR: 0.72(0.58-0.91).

Conclusions: Changes in BMI and decrease in triglycerides and WHR are related to lower skin-cancer risk, whereas increase in HbA1c may elevate risk in individuals younger than 45 at baseline. These findings highlight the importance of non-sunlight-related risk factors for skin-cancer prevention and the need for further research into underlying mechanisms.

Impact: This study contributes to the broader understanding of how metabolic health impacts skin-cancer development, offering potential avenues for targeted prevention strategies.

Background: The association between skeletal muscle and adipose tissue (body composition) and early response using positron emission tomography (PET) in pediatric Hodgkin lymphoma (HL) remains unstudied.

Methods: Patients enrolled on Children's Oncology Group studies AHOD0031 (intermediate-risk HL) and AHOD0831 (high-risk HL) with digital abdominal computed tomography (CT) scans at diagnosis and PET scans after 2 cycles (PET2) were included. Two consecutive slices at the third lumbar vertebra were identified and skeletal muscle index (SMI, in cm2/m2) and total adipose tissue index (TATI, in cm2/m2) were calculated using sliceOmatic (Magog, Canada) and height at diagnosis. SMI and TATI were divided into quintiles (Q1 [lowest] to Q5 [highest]). Body mass index (BMI) was calculated using height and weight at diagnosis. The association between baseline body composition (SMI, TATI, BMI) and positive PET2 was examined using logistic regression, adjusting for age at diagnosis, sex, race/ethnicity, stage, histology, bulk disease and 'B' symptoms.

Results: Among 1,033 included patients, PET2 was positive in 314 (30.4%). SMI was not associated with positive PET2. Extremes of TATI were associated with positive PET2, when compared with the middle TATI quintile (reference: Q3; odds ratio [ORQ1]=1.63, 95% confidence interval [CI]=1.03-2.60, P=0.04; ORQ2=1.82, 95%CI=1.17-2.82, P=0.008; ORQ5=1.94, 95%CI=1.23-3.05, P=0.005). The association between BMI in obesity range and positive PET2 trended towards significance (OR=1.42, 95%CI=0.98-2.04, P=0.06; ref=normal weight).

Conclusions: Extremes of adipose tissue at diagnosis influences early response among pediatric HL.

Impact: Validation of results from this study could inform studies investigating body composition-based chemotherapy dosing.

Background: To evaluate the impact of Hispanic ethnic enclaves (EE) on the relationship between neighborhood disadvantage and overall survival (OS) in breast cancer (BCa) patients.

Methods: Data from BCa patients with stage I-IV disease diagnosed between 2005-2017 was used to analyze the effects of Area Deprivation Index (ADI) scores, a measure of neighborhood disadvantage, and census-tract level Hispanic density, a measure of EE, on OS using mixed-effects Cox regression models. The final model included the following individual-level factors (age, income, race, Hispanic/Latino origin, nativity, insurance status, and comorbidities (hypertension, diabetes, and body mass index) and clinical factors (National Comprehensive Cancer Network guideline-concordant treatment, stage, and receptor subtype).

Results: 5,387 patients were analyzed. 52% resided in Hispanic EE. Enclave residents were predominantly White (93%), with Cubans the predominant subgroup (37%). Overall, there were 1,040 deaths within the cohort. Patients residing in highly disadvantaged neighborhoods (ADI Tertile 3 [ADIT3]) within Hispanic EE experienced reduced HR compared to those outside of EE, evidenced by the interaction effect [EE x ADIT3 - HR (95% CI): 0.66 (0.44, 0.98)].

Conclusions: Hispanic EE may protect against mortality in BCa patients, suggesting positive social factors help combat negative effects of neighborhood disadvantage for patients. Understanding protective attributes of EE can help create effective cancer interventions and promote more equitable outcomes in minority populations.

Impact: This study found that EE may protect against mortality in BCa patients, suggesting positive social factors may help mitigate the negative effects caused by the neighborhood.