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

Although several retrospective studies have investigated the association of TP53 rs1042522 and ApoB rs693 with the risk of biliary tract cancer (BTC), results have been inconsistent. In this study, to provide evidence from a prospective study, we analyzed the association of these two genetic polymorphisms with BTC risk using data from the Japan Public Health Center-based Prospective Study. We conducted a case-cohort study with 152 BTC cases and 12,159 subcohort subjects and estimated HRs and 95% confidence intervals (CI) using a weighted Cox proportional hazards model. TP53 rs1042522 showed a statistically significant association with the risk of BTC (HR, 1.89; 95% CI, 1.27-2.82, in the recessive genetic model), whereas ApoB rs693 showed no apparent association. Of interest, TP53 rs1042522 seemed to be associated with BTC risk in a recessive model, but not in a dominant model. On comparison of three BTC subtypes, TP53 rs1042522 seemed to be associated with the incidence of gallbladder cancer and extrahepatic bile duct cancer (HR, 2.21; 95% CI, 1.14-4.28 and HR, 1.97; 95% CI, 1.00-3.88, respectively) but showed only a nonsignificant association with intrahepatic bile duct cancer (HR, 1.58; 95% CI, 0.63-3.96). In this prospective case-cohort study, we found evidence to support an association between the TP53 rs1042522 polymorphism and the risk of BTC. The null finding for ApoB rs693 might be due to the extremely low T-allele frequency (4.4%) in the study population.

Prevention relevance: This prospective study highlights the effect of TP53 rs1042522 on BTC risk in Japanese individuals. Identifying carriers of the high-risk CC genotype may facilitate targeted surveillance and early detection strategies, potentially reducing mortality and improving outcomes. Further large-scale studies are required to clarify environmental interactions and optimize prevention.

Higher T-cell infiltration in colorectal tumors has been associated with better prognosis. Evidence indicates that calcium signaling is essential for T-cell functioning. However, as it is unknown whether calcium intake influences T-cell infiltration, we investigated the association of calcium intake with T-cell subsets in the tumor microenvironment of colorectal cancer. In total, 943 participants from three cohort studies, for which data on tumor-infiltrating T cells and calcium intake were available, were included for these analyses. Immune cell infiltration was quantified by digital image analyses with machine learning algorithms using a customized 9-plex multispectral immunofluorescence assay (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and di-(4-amidinophenyl)-1H-indole-6-carboxamidine). Associations between prediagnostic calcium intake and densities of nonoverlapping subsets of epithelial and stromal tissue area T cells were assessed using multivariable binary or ordinal logistic regression analyses. A higher dietary calcium intake was positively associated with CD3+CD4-CD8- double-negative T-cell density in the epithelial (OR, 1.57; 95% confidence interval, 1.13-2.24) and stromal (OR, 1.24; 95% confidence interval, 1.06-1.45) tumor tissue areas. No other statistically significant associations were observed after correcting for multiple testing. In conclusion, dietary calcium intake was associated with a higher density of CD4-CD8- double-negative T cells in the epithelial and stromal tumor tissue areas but not with the infiltration of CD4+ or CD8+ T cells. More research is needed to further unravel the role of calcium in tumor-immune profiles and associations with clinical outcomes. Our findings offer a promising basis for further research.

Prevention relevance: Our research contributes to the understanding of how diet could influence immune cell infiltration in and around the tumor. Understanding which factors influence antitumor immune responses is of importance in the prevention of cancer recurrence and/or progression.

Cervical cancer is one of the most common cancers in women. Despite progress in prevention and success in early detection through cytologic screening and human papillomavirus (HPV) detection, there remains a challenge in triaging women appropriately to colposcopy and biopsy. We sought to validate the CervicalMethDx test, a precision DNA methylation classifier for cervical cancer detection, as a reflex test in women with HPV-positive samples. A blinded retrospective study was performed on well-characterized samples in PreservCyt media from a large referral clinical laboratory in the United States. DNA methylation was assessed in three gene promoters (ZNF516, FKBP6, and INTS1) and a control gene (β-actin) by quantitative real-time methylation-specific PCR (qMSP) analysis, using machine learning algorithms. We compared DNA methylation levels in HPV-positive patients presenting with lesions in the Pap test and cervical intraepithelial neoplasia grade 2 (CIN2) or CIN3 histologic diagnosis with DNA methylation levels in HPV-positive patients with lesions in the Pap test but no intraepithelial lesion or malignancy. The CervicalMethDx test correctly classified 95% of the CIN2 samples (n = 210), with 91% sensitivity, 100% specificity, and an area under the ROC curve (AUC) of 0.96, and 94% of CIN3 samples (n = 141), with 90% sensitivity, 100% specificity, and an AUC of 0.96. Moreover, the CervicalMethDx test correctly classified 94% of combined CIN2/CIN3 samples (n = 351), with 93% sensitivity, 97% specificity, and an AUC of 0.96. CervicalMethDx demonstrated strong discriminatory power for identifying CIN2/CIN3 risk and may complement current triage strategies for colposcopy referral. Prospective, population-based studies, including those in low-resource settings, are needed for further evaluation.

Prevention relevance: The CervicalMethDx test integrates DNA methylation analysis and machine learning to improve early detection of high-grade cervical lesions (high-grade squamous intraepithelial lesions), offering a noninvasive, cost-effective screening tool. Enhanced risk stratification and overtreatment reduction expand equitable access to precision prevention programs. Further validation will clarify CervicalMethDx's alignment with global cervical cancer prevention strategies.

Precision prevention trials are biologically driven interception studies conducted in high cancer risk groups. These are smaller, potentially faster, cheaper, and more commercially attractive than traditional large-scale population prevention studies. In this article, we discuss the key challenges of conducting precision prevention research and their mitigations.

Black individuals are disproportionately burdened by prostate cancer compared with White individuals. The mitochondrion is an untapped source for prostate cancer biomarkers, and previous work has shown that altered mitochondrial DNA (mtDNA) copy number is linked to mitochondrial dysfunction and tumorigenesis. We assess whether mtDNA copy number is altered in patients with and without prostate cancer in a racially specific manner. Circulating cell-free mtDNA copy number from plasma and mtDNA copy number from white blood cells (WBC) were measured in 199 patients undergoing biopsy (50:50 White cases/controls and 50:49 Black cases/controls). mtDNA copy number was determined via Droplet Digital PCR. Logistic regressions tested associations between mtDNA and prostate cancer by race. The AUC was compared between covariate-only models and models with mtDNA. In both plasma and WBCs, mtDNA copy number was significantly increased in cases compared with controls in White patients, but not in Black patients. Interestingly, Black controls had higher mtDNA copy number levels than White controls. Multivariable analysis revealed significant associations of plasma mtDNA and WBC mtDNA with prostate cancer for White patients only. Elevated mtDNA copy number was more accurate in predicting prostate cancer in White patients than in Black patients. Higher mtDNA copy number levels were associated with prostate cancer in both Black and White patients. Plasma mtDNA may be more accurate than WBC mtDNA in predicting prostate cancer incidence in Black men. Overall, Black controls had higher mtDNA copy number levels than White controls, suggesting mtDNA copy number may be implicated in prostate cancer health disparities.

Prevention relevance: Our study shows that mtDNA copy number is a significant predictor of prostate cancer in White individuals, suggesting its potential use in early detection and prevention strategies. The absence of this association in Black individuals highlights the need for race-specific biomarkers in prostate cancer prevention efforts.

Obesity is a global menace that has impacted more than 14% of adults worldwide and more than a third of Americans. Importantly, obesity is associated with an increased risk of more than 13 types of cancer and worse outcomes, including increased mortality. This review focuses on the importance of considering obesity and metabolic dysfunction in cancer risk as part of the NCI's funded consortium known as the Metabolic Dysfunction and Cancer Risk Program. It describes previous and ongoing mouse models used in studies conducted by Metabolic Dysfunction and Cancer Risk Program consortium members, as well as other relevant studies. Most cancer studies examine tumor progression, metastasis, or recurrence, which are consequences following tumor onset; however, this approach does not consider risk per se. To truly model cancer risk, parameters to measure include the quantification of cancer onset, measured as incidence or latency. Investigators must be cognizant of many factors in study design, including the choice of cancer model and genetic strain. Preclinical approaches addressing risk typically include genetically engineered mouse models or the administration of irritants or carcinogens. We also discuss the transplantation of cells or tumors such as allografts or xenografts, with a focus on tumor rejection or regression to approximate cancer risk, not cancer progression. Herein, we highlight two cancers, breast and colorectal cancers, in which risk is associated with obesity and discussed varied murine model approaches, as well as key findings that explore cancer risk, prevention, or interception.

Smoking cessation following a cancer diagnosis is associated with improved outcomes, including reduced overall mortality. We searched the websites of 64 NCI-designated cancer centers that provide clinical cancer care to adults for webpages about smoking cessation and assessed the quality of the available content. Thirty-five of 64 (55%) websites hosted smoking cessation-focused webpages. Of those 35 webpages, 20 (57%) explicitly stated that smoking cessation decreases overall mortality, 8 (23%) included information about smoking cessation medications, 9 (26%) offered behavioral counseling tips such as setting a quit date or advising on habit replacement, and 11 (31%) described the risks and benefits of e-cigarette use. Links to other established smoking cessation organizations were evaluated; 15 (43%) webpages linked to smokefree.gov, 20 (57%) listed the phone numbers for state or national quitlines, and 5 (14%) described the Cancer Center Cessation Initiative. The average estimated reading level of the webpages was 10.5. These findings suggest that cancer center websites, which patients may access for trustworthy online medical information, often lack actionable and/or comprehensible information to help patients with cancer quit smoking. There is an opportunity to strengthen online communication to patients about effective smoking cessation strategies, which may help patients live longer and healthier lives.

Prevention relevance: Smoking cessation is paramount to preventing the onset of cancer, and in those who have a cancer diagnosis, quitting smoking will improve outcomes and also help reduce the risk of developing a second cancer.

Smoking cessation following a cancer diagnosis is associated with improved outcomes, including reduced overall mortality. We searched the websites of 64 National Cancer Institute designated cancer centers that provide clinical cancer care to adults for webpages about smoking cessation and assessed the quality of the available content. 35 of 64 (55%) websites hosted smoking cessation-focused webpages. Of those 35 webpages, 20 (57%) explicitly stated that smoking cessation decreases overall mortality, 8 (23%) included information about smoking cessation medications, 9 (26%) offered behavioral counseling tips such as setting a quit date or advising on habit replacement and 11 (31%) described the risks and benefits of e-cigarette use. Links to other established smoking cessation organizations were evaluated; 15 (43%) webpages linked to smokefree.gov, 20 (57%) listed the phone numbers for state or national quitlines, and 5 (14%) described the Cancer Center Cessation Initiative. The average estimated reading level of the webpages was 10.5. These findings suggest that cancer center websites, which patients may access for trustworthy online medical information, often lack actionable and/or comprehensible information to help patients with cancer quit smoking. There is an opportunity to strengthen online communication to patients about effective smoking cessation strategies, which may help patients live longer and healthier lives.

Colorectal cancer incidence is increasing in Korea, emphasizing the need to identify its risk factors. Serum lipids may influence colorectal cancer risk, but evidence is conflicting. We examined the associations between serum lipids and colorectal cancer risk in Koreans. Using data from the Korean Genome and Epidemiology Study's Health Examinees cohort, we assessed serum low-density lipoproteins, high-density lipoproteins, triglycerides (TG), and total cholesterol among those who did not use lipid-lowering drugs. Dyslipidemia and its subcategories were defined using established clinical thresholds. Cancer cases were identified via the national cancer registry. Associations between lipids and cancers were evaluated using Cox regression. Subgroup analyses were conducted by sex, age, diabetes, and prior screening experience, along with sensitivity analyses based on follow-up duration. During a median follow-up of 9.1 years, 821 new colorectal cancer cases occurred among 111,330 participants of 40 to 69 years of age (38,455 men and 72,875 women). For colorectal cancer, elevated TG [Q4 vs. Q1: HR = 1.32; 95% confidence interval (CI), 1.07-1.62; P-trend = 0.02] and total cholesterol (Q4 vs. Q1: HR = 1.22; 95% CI, 1.00-1.51) increased the risk. For colon cancer, high TG increased the risk (Q4 vs. Q1: HR = 1.42; 95% CI, 1.08-1.86; P-trend = 0.01). Those with hypertriglyceridemia, compared with those without, showed increased risk (HR = 1.42; 95% CI, 1.07-1.87) for rectal cancer, whereas other lipids showed no significant associations. Similar but attenuated results were found in the subgroup analyses among participants ≥50 years of age. TG was associated with colorectal, colon, and rectal cancers in Koreans. Findings suggest that lipid levels may be relevant to colorectal cancer prevention strategies.

Prevention relevance: Our findings highlight serum lipids as potential modifiable risk factors for colorectal cancer in Koreans. These results support lipid management as a preventive strategy, informing public health efforts. Targeted lipid control programs may reduce colorectal cancer risk, particularly among high-risk individuals, warranting further evaluation of lipid-lowering therapies for prevention.