Cancer Epidemiology Biomarkers & Prevention最新文献

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

Methods: Data from patients with stage I to IV breast cancer diagnosed between 2005 and 2017 were 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 overall survival using mixed-effects Cox regression models. The final model included the 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: A total of 5,387 patients were analyzed. Fifty-two percent 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) within Hispanic EE experienced reduced HR compared with those outside of EE, evidenced by the interaction effect {EE × ADI tertile 3 - HR [95% confidence interval (CI)], 0.66 (0.44-0.98)}.

Conclusions: Hispanic EE may protect against mortality in patients with breast cancer, suggesting that positive social factors help combat negative effects of neighborhood disadvantage for patients. Understanding the 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 patients with breast cancer, suggesting that positive social factors may help mitigate the negative effects caused by the neighborhood.

Background: Few studies have examined how cancer incidence varies by the country of origin among US Hispanic/Latino adults. In this study, we describe the incidence rates (IR) of cancer overall and for screen-detectable, tobacco-related, and obesity-related cancers among 16,415 participants in the Hispanic Community Health Study/Study of Latinos, an ongoing population-based cohort study of Hispanic/Latino adults from diverse backgrounds.

Methods: Cohort participant records were linked to the state cancer registries in New York, Florida, California, and Illinois to ascertain cancer incidence from baseline (2008-2011) through 2021. We estimated weighted age-adjusted IRs and age- and sex-adjusted HRs.

Results: Over a mean follow-up of 10.7 (SD = 2.0) years, 715 incident invasive cancers were diagnosed including 118 female breast, 102 prostate, and 79 bronchus and lung cancers. The IR of all cancers combined was 26.2 [95% confidence interval (CI), 22.6-30.2] per 10,000 (10K) person-years (py). The IRs were lowest among persons of Mexican descent [IR, 19.0 (95% CI, 15.0-24.1) per 10K py] and highest for those of Puerto Rican [IR, 36.6 (95% CI, 28.4-47.0) per 10K py] descent. Compared with those of Mexican descent, those of Puerto Rican, Cuban, and Dominican descent had higher hazards of cancer incidence; the incidence of obesity-related (HR, 2.37; 95% CI, 1.43-3.95) and tobacco-related (HR, 3.00; 95% CI, 1.58-5.71) cancers was also the highest among Puerto Ricans.

Conclusions: Cancer IRs varied by Hispanic/Latino heritage and were masked when Hispanics/Latinos were aggregated into a single group.

Impact: Understanding disparities in cancer risk by Hispanic/Latino heritage may help tailor cancer prevention and control strategies.

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

Methods: Data on oropharyngeal cancer were collected from PBCRs (1988-2020). Age-standardized rates were calculated from 2000 onward 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 oropharyngeal cancer cases were recorded across 30 PBCRs (1988-2020). Most cases involved males (81.58%) ages 55 to 59 years (17.06%). The oropharynx 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 (3.1-9.4/100,000). Incidence trends increased for 10 PBCR regions in males and 6 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 oropharyngeal cancer in Brazil differs among regions, with higher rates observed in the south and southeast. The prevalence of the human papillomavirus-attributable fraction for oropharyngeal cancer is unknown.

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

Background: The stromal microenvironment (SME) is integral to breast cancer biology, impacting metastatic proclivity and treatment response. Emerging data indicate that host factors may impact the SME, but the relationship between prediagnostic host factors and SME phenotype remains poorly characterized, particularly among women of African ancestry.

Methods: We conducted a case-only analysis involving 792 patients with breast cancer (17-84 years) from the Ghana Breast Health Study. High-accuracy machine-learning algorithms were applied to standard H&E-stained images to characterize SME phenotypes [including percent tumor-associated connective tissue stroma, Ta-CTS (%); tumor-associated stromal cellular density, Ta-SCD (%)]. Associations between prediagnostic host factors and SME phenotypes were assessed in multivariable linear regression models.

Results: Decreasing Ta-CTS and increasing Ta-SCD were associated with aggressive, mostly high-grade tumors (P-value < 0.001). Several prediagnostic host factors were associated with Ta-SCD independently of tumor characteristics. Compared with nulliparous women, parous women had higher levels of Ta-SCD [mean (standard deviation, SD) = 31.3% (7.6%) vs. 28.9% (7.1%); P-value = 0.01]. Similarly, women with a positive family history of breast cancer had higher levels of Ta-SCD than those without family history [mean (SD) = 33.0% (7.5%)] vs. 30.9% (7.6%); P-value = 0.03]. Conversely, increasing body size was associated with decreasing Ta-SCD [mean (SD) = 31.6% (7.4%), 31.4% (7.3%), and 30.1% (8.0%) for slight, average, and large body sizes, respectively; P-value = 0.005].

Conclusions: Epidemiological risk factors were associated with varying degrees of stromal cellularity in tumors, independently of clinicopathological characteristics.

Impact: The findings raise the possibility that epidemiological risk factors may partly influence tumor biology via the stromal microenvironment. See related In the Spotlight, p. 459.

Background: Worldwide trends support the increasing contribution of hepatic steatosis to the incidence of hepatocellular carcinoma (HCC). This study investigates if similar changes are seen in Hawaii, where the incidence of HCC is higher than in most of the United States.

Methods: This is a retrospective study of 1,651 patients diagnosed with HCC (1991-2023) that includes 60% to 70% of HCC cases in Hawaii. We evaluated changes in patient demographics, risk factors, and disease etiology over the past three decades.

Results: From 1991 to 2023, there were significant increases in the proportion of HCC cases attributable to metabolic dysfunction-associated steatotic liver disease (MASLD), coinciding with an increase 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. Hepatitis C virus (HCV)-associated cases increased through 2015 and then tapered, whereas Hepatitis B virus (HBV)-associated cases decreased through 2020. There was no significant change in the proportion of alcohol-associated cases.

Conclusions: Although HBV continues to be a major contributor to HCC in Hawaii, HCV-related HCC cases have tapered, whereas metabolic risk factors for HCC and cases attributable to MASLD have increased over time, paralleling 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 three decades.

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

Methods: A total of 31,883 participants in a large-scale population-based screening trial (Hua County, China) were enrolled to develop the model. Severe dysplasia and above cases identified at screening or follow-up were defined as the outcome. We calculated the absolute risk in three steps: (i) constructing a relative risk model using logistic regression, (ii) calculating the age-specific baseline hazard, and (iii) 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 severe dysplasia and above cases were detected. The relative risk model consisted of old age, male gender, an irregular meal pattern, a preference for hot or hard food, a BMI of less than 22 kg/m2, and ESCC family history. The AUC was 0.753 (95% confidence interval, 0.749-0.757). The averaged 5-and 10-year absolute risk were 0.53% and 1.30% among participants. Based on our model, we developed an online calculator and 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 the 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: Higher concentration of insulin-like growth factor-1 (IGF-1) increases postmenopausal breast cancer risk, but evidence for insulin and c-peptide is limited. Furthermore, not all studies have accounted for potential confounding by biomarkers from other biological pathways, and not all were restricted to estrogen receptor (ER)-positive breast cancer.

Methods: This was a case-cohort study of 1,223 postmenopausal women (347 with ER-positive breast cancer) from the Melbourne Collaborative Cohort Study. We measured insulin, c-peptide, IGF-1, insulin-like growth factor binding protein-3, and biomarkers of inflammatory and sex-steroid hormone pathways. Poisson regression with a robust variance estimator was used to estimate risk ratios (RR) and 95% confidence intervals (95% CI) for ER-positive breast cancer per doubling plasma concentration and for quartiles, without and with adjustment for other, potentially confounding biomarkers.

Results: ER-positive breast cancer risk was not associated with doubling of insulin (RR = 0.97, 95% CI, 0.82-1.14) or c-peptide (RR = 1.01, 95% CI, 0.80-1.26). Risk seemed to decrease with doubling IGF-1 (RR = 0.80, 95% CI, 0.62-1.03) and insulin-like growth factor binding protein-3 (RR = 0.62, 95% CI, 0.41-0.90). RRs were not meaningfully different when exposures were modeled as quartiles. RRs were less than unity but imprecise after adjustment for inflammatory and sex-steroid hormone biomarkers.

Conclusions: Circulating insulin, c-peptide, and IGF-1 were not positively associated with risk of ER-positive breast cancer in this case-cohort analysis of postmenopausal women.

Impact: Associations between insulin and c-peptide and risk of ER-positive breast cancer in postmenopausal women are likely to be weak.

Background: Parity and breastfeeding are associated with systemic changes in maternal inflammation and reduced risk of ovarian cancer, but little is known about their impact on the ovarian tumor immune microenvironment.

Methods: We evaluated the associations of self-reported parity and history of breastfeeding with tumor-infiltrating T cells among 1,706 ovarian carcinoma cases with tumor tissue collected across four studies. The abundance of tumor-infiltrating T cells was measured by multiplex immunofluorescence in tumor tissue microarrays. ORs and 95% confidence intervals (CI) for the positivity of tumor immune cells were calculated using beta-binomial models and stratified by histotype.

Results: Compared with ovarian tumors in nulliparous women, there was no association between parity and ovarian tumor T-cell abundance among all histotypes combined but suggestion of increased cytotoxic T cells and T-cell exhaustion among parous women with clear-cell tumors. When restricted to parous women, history of breastfeeding was associated with increased odds for all T-cell types [i.e., total T, cytotoxic T, helper T (Th), regulatory T, and exhausted T cells], with ORs ranging from 1.11 to 1.42. For every 6 months of breastfeeding, we observed increased odds of activated Th-cell infiltration (CD3+CD4+CD69+; OR, 1.13, 95% CI, 0.99-1.29), with a similar association for high-grade serous tumors, but lower odds in clear-cell tumors (OR, 0.43, 95% CI, 0.21-0.87).

Conclusions: History of breastfeeding may alter the ovarian tumor immune microenvironment by modulating the abundance of tumor-infiltrating T cells.

Impact: Although replication is required, history of breastfeeding may play a role in the activation of the ovarian tumor immune response.

Breast cancer incidence rates for Black and White women in the United States have recently converged, with mortality rates remaining disproportionately higher for Black women. This disparity is more pronounced given the higher prevalence of hormone receptor-negative tumors in women of African ancestry, tumors which are more aggressive and harder to treat. Abubakar and colleagues' analysis of 792 breast cancer cases from the Ghana Breast Health Study offers new insights into the stromal tumoral microenvironment in sub-Saharan African women. Using machine learning techniques, tumor-associated stromal cellular density was associated with more aggressive tumors, higher tumor grade, and parity versus nulliparity, whereas breastfeeding did not significantly affect stromal characteristics. This commentary spotlights the innovative combination of traditional diagnostic methods, such as hematoxylin and eosin staining, with machine learning techniques within the Ghana Breast Health Study as a promising approach for improving breast cancer prognostication in low-resource settings. Moreover, this commentary underscores the need for inclusive, equity-driven research approaches that consider biological factors, host factors, and social and structural drivers of health when examining breast cancer disparities. See related article by Abubakar et al., p. 462.

Background: Excess adiposity has been associated with an increased risk of several types of cancer. The relationship between fat tissue distribution in the body and these outcomes is less well known. Using data from the UK Biobank imaging substudy, we evaluated the prospective relationship between MRI-derived measurements of adipose tissue distribution and the risk of the major site-specific cancers associated with obesity.

Methods: Between 2014 and 2023, MRI measurements on adipose tissue distribution and volume were obtained from 49,044 (52.2% women) cancer-free UK Biobank participants. Quantitative MRI data included volumes of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT), total abdominal fat/height squared (TAT/h2), and muscle fat infiltration (MFI). Cox proportional hazard models adjusted for cancer-specific risk factors were used to generate HRs and 95% confidence intervals.

Results: Incident cancer cases of the breast (N = 179), endometrium (n = 30), colorectum (n = 145), and kidney (n = 50) were ascertained over a median follow-up of 4.5 years. In women, VAT, TAT/h2, and MFI were positively associated with a risk of postmenopausal breast cancer, and ASAT was associated with an increased risk of endometrial cancer. In men, VAT and TAT/h2 were positively associated with a risk of colorectal cancer, whereas ASAT was associated with an increased risk of kidney cancer.

Conclusions: The present study showed that increasing volumes of VAT, ASAT, and MFI were associated with cancers at specific organ sites, indicating a potential role for adipose tissue distribution in influencing cancer risk.

Impact: Both visceral and subcutaneous fat may have an impact on the risk of certain cancers.