Cancer prevention research (Philadelphia, Pa.)最新文献

The United States Preventive Services Task Force updated its lung cancer screening (LCS) recommendations in 2021, and the American Cancer Society (ACS) updated its LCS guidelines in 2023. Each update expanded screening eligibility criteria, thus increasing the total number of individuals eligible for LCS. However, it is not clear whether different population subgroups benefit equally from the recent updates of LCS recommendations in terms of becoming newly eligible. We identified 85,395 individuals who were between 50 and 80 years old, smoked cigarettes formerly or currently, and did not have a history of lung cancer from the Behavioral Risk Factor Surveillance System survey of 2022. We used descriptive analysis to illustrate the weighted proportions of the newly screening-eligible population among different subgroups. We also applied multivariable logistic regression models to estimate the ORs of being newly eligible for LCS under each LCS recommendation update in 2021 and 2023. For both LCS updates, individuals who were non-Hispanic White males and had chronic obstructive pulmonary disease were significantly more likely to become newly eligible for LCS. A significantly larger proportion of older-age individuals became newly eligible under the 2023 ACS guideline. Noticeably, both guideline updates substantially increased the population eligible for screening among males and older individuals, two groups experiencing the majority of lung cancer incidence and mortality. Results also indicate that the screening eligibility criteria updates did not increase the OR of being eligible among racial/ethnic minority and female subgroups. Prevention Relevance: This study examines the evolving LCS guidelines and their public health impact. Analyzing the 2021 United States Preventive Services Task Force and 2023 ACS updates, we show expanded eligibility but persistent disparities among sociodemographic groups. Our findings highlight the need for targeted interventions to improve screening uptake and promote equitable, inclusive prevention strategies.

Screening digital breast tomosynthesis (DBT) aims to identify breast cancer early when treatment is most effective, leading to reduced mortality. In addition to early detection, the information contained within DBT images may also inform subsequent risk stratification and guide risk-reducing management. Using transfer learning, we refined a model in the Joanne Knight Breast Health Cohort at Washington University, a cohort of 5,066 women with DBT screening (mean age, 54.6), among whom 105 were diagnosed with breast cancer (26 ductal carcinoma in situ). We applied the model to external data from the Emory Breast Imaging Dataset, a cohort of 7,017 women free from cancer (mean age, 55.4), among whom 111 pathology-confirmed breast cancer cases were diagnosed more than 6 months after initial DBT (17 ductal carcinoma in situ). We obtained a 5-year AUC of 0.75 [95% confidence interval (CI), 0.73-0.78] in the internal validation. The model validated in external data gave an AUC of 0.72 (95% CI, 0.69-0.75). The AUC was unchanged when age and Breast Imaging-Reporting and Data System density were added to the model with synthetic DBT images. The model significantly outperforms the Tyrer-Cuzick model, with a 5-year AUC of 0.56 (95% CI, 0.54-0.58; P < 0.01). Our model extends risk prediction applications to synthetic DBT, provides 5-year risk estimates, and is readily calibrated to national risk strata for clinical translation and guideline-driven risk management. The model could be implemented within any digital mammography program. Prevention Relevance: We develop and externally validate a 5-year risk prediction model for breast cancer using synthetic DBT and demonstrate clinical utility by calibrating to the national risk strata as defined in breast cancer risk management guidelines.

Cancer screening lowers morbidity and mortality from cancer and is cost-effective. The COVID-19 pandemic upended cancer screening utilization in 2020 with data showing a deficit in screened patients in 2020 and 2021 as compared with 2019, with return to 2019 baseline screening levels by December 2022. The cumulative shortfall in screenings, lasting nearly 3 years into the pandemic, is predicted by models to generate an incremental population cancer burden in the out-years of the models. Recovery of screening rates may vary based on the racial or ethnic population, and time will tell if there is an uneven burden of future cancers that worsen cancer incidence and mortality in those populations, some even after years of gains of reducing disparities for cancer screening. For some cancer screenings, particularly cervical and colorectal cancers, use of at-home noninvasive tests may increase screening participation overall across multiple populations and help mitigate some of the screening shortfalls from 2020 to 2022 by elevating numbers of the population screened. For colorectal cancer, new additional comparably sensitive or ease-of-use noninvasive screening tests are being added for utilization.

Colorectal cancer is highly preventable with timely screening, but screening modalities are widely underused, especially among those of low individual-level socioeconomic status (SES). In addition to individual-level SES, neighborhood-level SES may also play a role in colorectal cancer screening completion through less geographic access to health care, transportation, and community knowledge of and support for screenings. We investigated the associations of neighborhood SES using a census tract-level measure of social and economic conditions with the uptake of colonoscopy and stool-based testing. We utilized data from the Southern Community Cohort Study, a large, prospective study of English-speaking adults ages 40 to 79 from the southeastern United States with 65% of participants identifying as non-Hispanic Black and 53% having annual household income <$15,000. Neighborhood SES was measured via a neighborhood deprivation index compiled from principal component analysis of 11 census-tract variables in the domains of education, employment, occupation, and poverty; screening was self-reported at the baseline interview (2002-2009) and follow-up interview (2008-2012). We found that participants residing in the lowest SES areas had lower odds of ever undergoing colonoscopy (ORQ5vsQ1 = 0.75; 95% confidence interval, 0.68-0.82) or stool-based colorectal cancer testing (ORQ5vsQ1 = 0.71; 95% confidence interval, 0.63-0.80) while adjusting for individual-level SES factors. Associations were consistent between neighborhood SES and screening in subgroups defined by race, sex, household income, insurance, or education (P > 0.20 for all interaction tests). Our findings suggest that barriers to screening exist at the neighborhood level and that residents of lower SES neighborhoods may experience more barriers to screening using colonoscopy and stool-based modalities. Prevention Relevance: This study presents evidence that persons living in lower SES neighborhoods use colorectal cancer screening modalities at lower rates. Screening is highly preventive of colorectal cancer, but it has limited benefit if it cannot be utilized. Addressing neighborhood-level barriers to screening may improve socioeconomic disparities in colorectal cancer.

Experimental studies have shown that dietary isothiocyanates reduced cellular proliferative marker Ki-67 and increased apoptotic markers caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in animals, but human data are lacking. The present study was to assess whether sulforaphane would stop/reverse the progression of bronchial histopathology, reduce the Ki-67 index, and/or increase caspase-3 and TUNEL indices in humans. A randomized clinical trial (NCT03232138) was conducted in former smokers. Forty-three subjects were randomly assigned to the placebo or the treatment with a potential daily dose of 95 μmol sulforaphane for 12 months. The endpoints were the changes in histopathology scores and Ki-67, caspase-3, and TUNEL indices in post- versus pretreatment bronchial biopsies. Thirty-seven participants (17 in the sulforaphane and 20 in the placebo group) completed the study. Supplementation of sulforaphane did not show significant impact on bronchial histopathology but significantly reduced the Ki-67 index with a 20% decrease in the sulforaphane group and a 65% increase in the placebo (P = 0.014). The difference was even greater in high-density (3+) positive Ki-67, with a 44% decrease in the sulforaphane group compared with a 71% increase in the placebo (P = 0.004). Higher bioavailability of sulforaphane was correlated with greater reduction of the Ki-67 index (P for trend = 0.019). Sulforaphane treatment had no impact on the caspase-3 or TUNEL index in bronchial biopsies. No severe adverse event was observed in the study participants. The findings of oral sulforaphane that significantly reduced the Ki-67 index in bronchial tissue support further development as a potential chemopreventive agent against lung cancer development. Prevention Relevance: High intake of cruciferous vegetables and their sulforaphane is associated with lower incidence of lung cancer in humans and animal models. This clinical trial has demonstrated that oral supplementation of sulforaphane for 12 months significantly reduced the Ki-67 index, a potential surrogate endpoint of biomarkers for lung cancer risk.

Levonorgestrel-releasing intrauterine system (LNG-IUS) use is approved by the FDA for contraception and heavy menorrhagia. More importantly, it effectively treats endometrial hyperplasia, a precursor to endometrial cancer. Therefore, LNG-IUS use is associated with potential endometrial cancer risk reduction, but current use patterns in the United States are unknown. We analyzed LNG-IUS use prevalence among women ages 18 to 50 years using a weighted statistical analysis of the 2017 to 2019 National Survey of Family Growth. Summary statistics were stratified by race and ethnic group and known endometrial cancer sociodemographic and health risk factors and assessed statistically with bivariate Rao-Scott χ2 tests. A multivariable logistic regression model was developed to explore LNG-IUS use predictors. Current LNG-IUS use in the United States was 6.9% [95% confidence interval (CI), 5.9%-8.1%]. LNG-IUS use was lower in Hispanic women compared with White women [adjusted OR (AOR), 0.7; 95% CI, 0.5-1.0]. Compared with women with ≤high school education, LNG-IUS use was higher for women with ≥college degree (AOR, 2.0; 95% CI, 1.3-3.1). Parous (AOR, 2.6; 95% CI, 1.7-3.9) and insured (AOR, 1.7; 95% CI, 1.0-3.1) women had higher odds of LNG-IUS use, whereas women with diabetes (AOR, 0.3; 95% CI, 0.1-0.7) had lower odds of LNG-IUS use. No differences in LNG-IUS use were observed by endometrial cancer risk factors of women's body mass index, age of menarche, hypertension, and personal history of cancer. More research is needed to establish the potential benefits of LNG-IUS use on endometrial cancer, which will further highlight potential opportunities for population-level primary prevention to address the growing incidence of endometrial cancer. Prevention Relevance: This study describes the characteristics of American women using the LNG-IUS. Reproductive-age women (especially Hispanic, with lower education, nulliparous, uninsured, and with diabetes) have lower LNG-IUS use odds. These groups may benefit from LNG-IUS use for endometrial cancer primary prevention, conditioned that LNG-IUS use is proven effective in reducing endometrial cancer incidence.

Gastric cancer is the fifth most common cancer and the fifth leading cause of cancer deaths worldwide. Chronic infection by the bacterium Helicobacter pylori is the most prominent gastric cancer risk factor, but only 1% to 3% of infected individuals will develop gastric cancer. Cigarette smoking is another independent gastric cancer risk factor, and H. pylori-infected smokers are at a 2- to 11-fold increased risk of gastric cancer development, but the direct impacts of cigarette smoke (CS) on H. pylori pathogenesis remain unknown. In this study, male C57BL/6 mice were infected with H. pylori and began smoking within 1 week of infection. The mice were exposed to CS 5 days/week for 8 weeks. CS exposure had no notable impact on gross gastric morphology or inflammatory status compared with filtered-air (FA) exposed controls in mock-infected mice. However, CS exposure significantly blunted H. pylori-induced gastric inflammatory responses, reducing gastric atrophy and pyloric metaplasia development. Despite blunting these classic pathological features of H. pylori infection, CS exposures increased DNA damage within the gastric epithelial cells and accelerated H. pylori-induced dysplasia onset in the INS-GAS gastric cancer model. These data suggest that cigarette smoking may clinically silence classic clinical symptoms of H. pylori infection but enhance the accumulation of mutations and accelerate gastric cancer initiation. Prevention Relevance: These findings suggest that cigarette smoking suppresses pathophysiological hallmarks of H. pylori infection while accelerating gastric carcinogenesis. Therefore, smokers should receive screening for H. pylori infection to reduce gastric cancer risk. See related Spotlight, p. 257.

The New England Bladder Cancer Study has recently reported an increased bladder cancer risk with occupational exposure to mononuclear aromatic organic solvents, including exposure to benzene, toluene, and xylene and their combination BTX. However, the mechanisms by which BTX influence bladder cancer are unclear. In this study, we evaluated the interaction between BTX and genetic markers in known bladder cancer susceptibility loci and in variants shown to impact the metabolism of these solvents. We used multivariate logistic regression to calculate the ORs, 95% confidence intervals, and P values for multiplicative interaction in 1,182 cases and 1,408 controls from a population-based case-control study from New England. Lifetime occupational exposure to benzene, toluene, xylene, and BTX were assessed using occupational histories and exposure-oriented modules in conjunction with a job-exposure matrix. Buccal cells from mouthwash samples were used to conduct genotyping. Subjects with the highest cumulative exposure to benzene and who carried a risk allele in rs72826305 (CASC15) had an increased risk of bladder cancer (OR = 2.56, 95% confidence interval, 1.28-5.12) compared with those never exposed with no risk alleles (P interaction = 0.03). Additional suggestive joint effects with benzene were evident for those carrying genetic risk variants in FGFR3 (P value = 0.01) and GSTT1 (P interaction = 0.007). Bladder cancer risk is higher among those exposed to BTX-containing solvents who also harbor common variants in CASC15, FGFR3, and GSTT1, adding to the evidence of a plausible link between these exposures and bladder cancer risk. Prevention Relevance: Our findings suggest that bladder cancer risk is higher among those exposed to BTX-containing solvents who also harbor common genetic polymorphisms associated with bladder cancer. The joint contribution of genetics and occupational exposures may play an important role in the etiology of bladder cancer.

The study by Morris and colleagues provides new insights into gastric cancer development, challenging the traditional Correa cascade model. Their findings show that cigarette smoke exposure accelerates dysplasia formation while reducing Helicobacter pylori-associated inflammation and metaplasia. This suggests that dysplasia may arise from tissue-resident stem cells rather than metaplastic cells. The study also supports the idea that metaplasia may play a protective role in maintaining epithelial integrity under chronic stress. These findings contribute to a better understanding of how environmental factors influence gastric carcinogenesis and may help refine approaches to prevention and treatment. See related article by Morris et al., p. 271.

The International Anal Neoplasia Society (IANS) has generated recommendations for anal cancer screening, identifying men who have sex with men (MSM) living with human immunodeficiency virus (HIV; MSM-LWH) ≥35 years and MSM not living with HIV (MSM-noHIV) ≥45 years as groups to prioritize. As high-resolution anoscopy (HRA) availability is still limited across Europe, a retrospective study was conducted to estimate the potential HRA referral rates of the Sexually Transmitted Infections (STI)/HIV center of a European capital city using IANS-recommended strategies. The study included participants in a program for the surveillance of anal intraepithelial neoplasia and anal human papillomavirus (HPV) natural history. MSM-LWH ≥35 years and MSM-noHIV ≥45 years with valid results for liquid-based anal cytology and HPV test at baseline were included. The following strategies were evaluated: cytology as a standalone test or with high-risk HPV (hrHPV) triage; hrHPV (with/without HPV16 genotyping) as a standalone test or with cytology triage; and cotesting with cytology and hrHPV (with/without HPV16 genotyping). Overall, 307 MSM were included (244 LWH, 79.5%). hrHPV as a standalone test led to the highest referral rate in both MSM-LWH and MSM-noHIV (74.6% and 55.6%, respectively). Cytology with hrHPV triage (without genotyping) and hrHPV with cytology triage resulted in the same referral rates (44.3% in MSM-LWH and 27.0% in MSM-noHIV). In settings with insufficient HRA capacity, only high-grade squamous intraepithelial lesions (HSIL) or atypical squamous cells-cannot exclude HSIL (4.9% and 9.5% for MSM-LWH and MSM-noHIV, respectively) and HPV16+ MSM (27.0% and 20.6%, respectively) would be referred to HRA. Adoption of IANS recommendations should balance the sensitivity of the screening algorithm and the HRA referral rate because the latter is a matter of concern in settings with limited HRA capacity. Prevention Relevance: Adopting the recent IANS recommendations for anal cancer screening in MSM may be challenging when HRA availability is limited. Estimating the HRA referral rates we would have using 12 different screening algorithms, we highlighted that application of these recommendations implies a careful analysis of the local resource capacity.