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

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.

Established risk factors for multiple myeloma, including obesity and sedentary lifestyles, are associated with well-known racial/ethnic disparities in disease risk. This review examines established risk determinants for multiple myeloma in Black adults, summarizes evidence linking lifestyle factors, including obesity, physical inactivity, and diet, to disease risk, and discusses energy balance interventions, including cultural tailoring, to mitigate multiple myeloma risk. We summarize current evidence for racial/ethnic disparities in risk factors for multiple myeloma, including unmodifiable heritable factors, modifiable contributors to obesity, including diet and physical activity, and barriers to meeting physical activity and healthful diet guidelines. With this evidence, we present considerations to research lifestyle interventions directed toward risk factors for multiple myeloma. Current foundational scientific evidence in energy balance interventions for cancer risk management is primarily supported in non-Hispanic White populations. Evidence for preventative exercise, diet, or lifestyle interventions for multiple myeloma among underrepresented populations is scarce. Research considerations are proposed to provide strategies utilizing community engagement, primary care education, and importantly, availability of exercise and dietary resources. The importance of tailoring exercise and dietary interventions is also underscored, in addition to generating clinical trial-based evidence to be equitable and beneficial for all populations.

The role of dietary fiber in colon cancer prevention remains controversial. We investigated its impact on antitumor immunity and the gut microbiota in APCmin/+ mice infected with enterotoxigenic Bacteroides fragilis. Mice were fed high-fiber, low-fiber, or chow diets, and the tumor burden, survival, cytokines, microbiota, and metabolites were analyzed. Contrary to the belief that high fiber inhibits tumor progression, it had no significant impact compared with chow diet. However, the low-fiber diet significantly reduced the tumor burden and improved survival. Mechanistically, high fiber increased proinflammatory cytokines and CD4+Foxp3+RORγt+IL-17A+ regulatory T cells, whereas low fiber enhanced anti-inflammatory cytokines and cytotoxic T cells. High fiber enriched microbial taxa associated with IL-17A+RORγt+ regulatory T cells and altered metabolites, including reduced tryptophan and increased short-chain fatty acids and bile acids. Low fiber produced opposite effects. These findings suggest that dietary fiber's effects on colon cancer depends on microbial infection and immune status, emphasizing the need for personalized dietary interventions in colon cancer management. Prevention Relevance: Dietary fiber's impact on colon cancer progression highlights the need for personalized dietary approaches, considering microbial infection and immune status.

Oral cancer is a major global health problem. It is commonly diagnosed at an advanced stage, although often preceded by clinically visible oral mucosal lesions, termed oral potentially malignant disorders, which are associated with an increased risk of oral cancer development. There is an unmet clinical need for effective screening tools to assist front-line healthcare providers to determine which patients should be referred to an oral cancer specialist for evaluation. This study reports the development and evaluation of the mobile detection of oral cancer (mDOC) imaging system and an automated algorithm that generates a referral recommendation from mDOC images. mDOC is a smartphone-based autofluorescence and white light imaging tool that captures images of the oral cavity. Data were collected using mDOC from a total of 332 oral sites in a study of 29 healthy volunteers and 120 patients seeking care for an oral mucosal lesion. A multimodal image classification algorithm was developed to generate a recommendation of "refer" or "do not refer" from mDOC images using expert clinical referral decision as the ground truth label. A referral algorithm was developed using cross-validation methods on 80% of the dataset and then retrained and evaluated on a separate holdout test set. Referral decisions generated in the holdout test set had a sensitivity of 93.9% and a specificity of 79.3% with respect to expert clinical referral decisions. The mDOC system has the potential to be utilized in community physicians' and dentists' offices to help identify patients who need further evaluation by an oral cancer specialist. Prevention Relevance: Our research focuses on improving the early detection of oral precancers/cancers in primary dental care settings with a novel mobile platform that can be used by front-line providers to aid in assessing whether a patient has an oral mucosal condition that requires further follow-up with an oral cancer specialist.