Cancer In High-risk Population Research Articles

Effect of Helicobacter pylori Eradication on Gastric Cancer Prevention: Updated Report From a Randomized Controlled Trial With 26.5 Years of Follow-up

Helicobacter pylori infection is considered as the most important risk factor in the pathogenesis of gastric cancer. This study aims to evaluate the long-term effects of H pylori eradication treatment on the incidence and mortality of gastric cancer among a high-risk population. This prospective, randomized, placebo-controlled trial was conducted in a high-risk area in southern China in July 1994. A total of 1630 asymptomatic, H pylori-infected individuals were randomly assigned to receive standard triple therapy for H pylori eradication (n= 817) or placebo (n= 813), and were followed up until December 2020. The primary outcome was incidence of gastric cancer. Total and cause-specific mortalities were the secondary outcomes. During 26.5 years of follow-up, 21 participants (2.57%) in the treatment arm and 35 (4.31%) in the placebo arm were diagnosed with gastric cancer. Participants receiving H pylori treatment had a lower incidence of gastric cancer compared with their placebo counterparts (hazard ratio [HR], 0.57; 95% CI, 0.33-0.98). More obvious risk reduction was observed among those without premalignant gastric lesions (HR, 0.37; 95% CI, 0.15-0.95) and those without dyspepsia symptoms at baseline (HR, 0.44; 95% CI, 0.21-0.94). Furthermore, compared with 32 cases of gastric cancer observed among 527 participants with persistent H pylori infection in the placebo group, only 16 were identified in 625 subjects with successful eradication in the treatment group (HR, 0.46; 95% CI, 0.26-0.83). However, there were no statistically significant differences for any mortality end points between the 2 groups. Eradication of H pylori might confer a long-term protection against gastric cancer in high-risk populations, especially for infected individuals without precancerous gastric lesions at baseline.

A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.

P68.09 Precision Cut Lung Slices Models for Lung Cancer Chemoprevention Investigations

Chemoprevention of lung cancer is key to reducing the burden of lung cancer in high-risk populations. However, studying chemoprevention mechanisms currently relies largely on animal models of lung cancer. While these in vivo studies are critical to support chemoprevention clinical trials, they are costly, time consuming, and require large numbers of animals. Precision-cut lung slices (PCLS) address these challenges by retaining the complexity of living tissue while enabling ex vivo studies of pathogenesis.

S1425 A Community-Based Screening Survey for Gastric Cancer in High-Risk Populations

S1425 A Community-Based Screening Survey for Gastric Cancer in High-Risk Populations

Cost Utility Analysis of a Pilot Study for the Korean Lung Cancer Screening Project.

PurposeThe aim of this study was to evaluate the cost utility of a pilot study of Korean Lung Cancer Screening Project.Materials and MethodsWe constructed a Markov model consisting of 26 states based on the natural history of lung cancer according to the Surveillance, Epidemiology, and End Results summary stage (localized, regional, distant). In the base case, people aged 55–74 years were under consideration for annual screening. Costs and quality-adjusted life years were simulated to calculate the incremental cost utility ratio. Sensitivity analyses were performed on the uncertainty associated with screening target ages, stage distribution, cost, utility, mortality, screening duration, and discount rate.ResultsThe base case (US$25,383 per quality-adjusted life year gained) was cost-effective compared to the scenario of no screening and acceptable considering a willingness-to-pay threshold of US$27,000 per quality-adjusted life years gained. In terms of the target age of screening, the age between 60 and 74 years was the most cost-effective. Lung cancer screening was still cost-effective in the sensitivity analyses on the cost for treatment, utility, mortality, screening duration, and less than 5% discount rates, although the result was sensitive to a rise in positive rates or variation of stage distribution.ConclusionOur results showed the cost-effectiveness of annual low-dose computed tomography screening for lung cancer in high-risk populations.

Thyroid cancer overdiagnosis revisited

BackgroundEvidence has accumulated showing that an increase in thyroid cancer incidence reflects overdiagnosis of clinically unimportant lesions due to the rise in the use of neck ultrasonography. In the manuscript we examine the hypothesis that the rise in thyroid cancer incidence in Russia is largely caused by overdiagnosis. Materials and methodsIncidence and mortality rates of thyroid cancer for Russia overall and its administrative regions were abstracted from the statistical database of the Ministry of Health of Russia. For incidence trends, we calculated the percentage change, linear regression coefficient and p-value. The calculation of excess cases was based on expected age-specific distributions assuming that the incidence of thyroid cancer increases exponentially with age, as predicted by the multistage model of carcinogenesis. FindingsOver the study period (1989–2015) the age standardized incidence of thyroid cancer has tripled in Russian women and doubled in men. Strong support for the hypothesis that the increase in thyroid cancer incidence may be artificial is evident from age-specific incidence trends: increases in incidence in middle age but not in older ages, thereby altering the age curves from the expected exponential shape to an “inverted U” shape. The number of observed cases of thyroid cancer exceeded the expected number by 138, 325 or 70 % of all cases diagnosed with thyroid cancer. We attribute the excess cases to detection by ultrasonography clinically unimportant lesions. This is supported by a very high incidence –to-mortality ratio, low case fatality, high and growing prevalence of thyroid cancer. ConclusionAlthough there is an evidence that exposure to iodine 131 (131I) is an important cause of the increase in incidence of thyroid cancer in high-risk populations, we have shown that this increase could largely be attributed to overdiagnosis associated with ultrasonography screening. Overdiagnosis is the only explanation of the increase in thyroid cancer incidence in low-risk regions.

Progress in cohort study of lung cancer in high-risk population in communities

The cohort study of lung cancer in high-risk population in communities in China was a part of Lung Cancer Cohort Study initiated in 2017 and funded by Precision Medicine Research of National Key Research and Development Program. Around 50 000 participants from the communities were enrolled from 7 cities in 7 regions in China. Information about the risk factors for lung cancer were collected and the populations at high risk for lung cancer were identified. Then, low-dose CT (LDCT) screening of lung cancer was conducted in the populations at high risk, and further information about the diagnosis of lung cancer cases and death cases were collected. Therefore, a community population-based cohort was established for lung cancer risk factor exposure survey, high risk population evaluation, LDCT screening and lung cancer case and death follow up. Meanwhile, biological samples were collected from all the participants in the cohort to support the future precision medicine research of lung cancer.

Abstract 109: Vaccination with Polyclonal Antibody Stimulator (PAS) prevents pancreatic carcinogenesis in the KRAS mouse model

Abstract Background: Survival from pancreatic cancer is poor in part because it is not recognized or treated in the precancerous or early cancer stages. Gastrin is expressed in the fetal pancreas but silenced in the adult pancreas. Gastrin is re-expressed in precancerous pancreatic intraepithelial neoplasia (PanINs) where it acts to promote epithelial growth and fibrosis of the extracellular matrix. When gastrin is knocked-out in KRAS mice, PanINs fail to progress to cancer. Polyclonal Antibody Stimulator (PAS) is a target-specific vaccine to gastrin that activates B and T-cells to neutralize the actions of gastrin Hypothesis: It was hypothesized that treatment of transgenic LSL-KrasG12D/+; P48-Cre (KC) mice with PAS will slow PanIN progression and prevent pancreatic cancer. Methods: Nineteen age-matched littermates of KC mice were divided into two groups: control/untreated (N=9) and PAS-treated (N=10). Starting when the mice were 3 months of age, when PanIN lesions are developing, the PAS-mice received an initiation dose of PAS 250µg subcutaneously (sc) at baseline, week 1 and week 3. The PAS-treated mice then received a booster dose of PAS 250µg sc every 4 weeks until the mice reached 8 months of age for a total of 4 boosters. The control mice were untreated. The pancreata were dissected and paraffin embedded for analysis. H&E stained slides were evaluated for PanIN stage, extent of PanINs, inflammation, and fibrosis by a pathologist blinded to the treatment. Sections were stained with Masson's trichrome for fibrosis analysis and arginase for M2 macrophages. Results: When euthanized at 8-months of age, 67% of the control mice had high grade PanIN-3 lesions and 33.3% had invasive carcinoma. In contrast, the histologic stage in the age-matched PAS- treated mice was significantly lower, with more stage PanIN-2 lesions and only 10% with invasive carcinoma. The volume of normal pancreas present in the PAS-treated mice was 60% greater than in the control mice. Quantitation of the extracellular matrix showed 50% less fibrosis in the mice vaccinated with PAS as compared to controls (P=0.0001). Pancreata of PAS-treated mice also had fewer M2-polarized tumor-promoting macrophages than control mice (P<0.001). Conclusion: Pancreatic cancer and the progression of PanIN lesions can be prevented by a vaccine that targets gastrin. PAS treatment alters the microenvironment rendering it less carcinogenic. This vaccine has the potential to decrease pancreatic cancer in high risk populations and to prevent recurrence in surgically treated patients. Citation Format: Jill P. Smith, Hong Cao, Bhaskar Kallakury, Teresa Phillips, Lynda Sutton, Allen Cato. Vaccination with Polyclonal Antibody Stimulator (PAS) prevents pancreatic carcinogenesis in the KRAS mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 109.

Determining cost-effectiveness of lung cancer screening in urban Chinese populations using a state-transition Markov model

ObjectivesThis study analyses the cost-effectiveness of annual low-dose CT (LDCT) screening of high-risk cancer populations in Chinese urban areas.DesignWe used a Markov model to evaluate LDCT screening from a sociological...

Tumor necrosis factor receptor signaling modulates carcinogenesis in a mouse model of breast cancer

Pro-inflammatory conditions have long been associated with mammary carcinogenesis and breast cancer progression. The underlying mechanisms are incompletely understood but signaling of pro-inflammatory cytokine TNFα through its receptors TNFR1 and TNFR2 is a major mediator of inflammation in both obesity and in the response of tissues to radiation, 2 known risk factors for the development of breast cancer. Here, we demonstrated the loss of one TNFR2 allele led to ductal hyperplasia in the mammary gland with increased numbers of mammary epithelial stem cell and terminal end buds. Furthermore, loss of one TNFR2 allele increased the incidence of breast cancer in MMTV-Wnt1 mice and resulted in tumors with a more aggressive phenotype and metastatic potential. The underlying mechanisms include a preferential activation of canonical NF-κB signaling pathway and autocrine production of TNFα. Analysis of the TCGA dataset indicated inferior overall survival for patients with down-regulated TNFR2 expression. These findings unravel the imbalances in TNFR signaling promote the development and progression of breast cancer, indicating that selective agonists of TNFR2 could potentially modulate the risk for breast cancer in high-risk populations.

Screening for Nasopharyngeal Cancer in High-Risk Populations: A Small Price to Pay for Early Disease Identification?

Screening for Nasopharyngeal Cancer in High-Risk Populations: A Small Price to Pay for Early Disease Identification?

Assessing barriers to genetic screening for hereditary breast, ovarian, and colon cancer in high-risk populations

Objective: The aim of this study was to identify barriers to genetic testing among individuals with a high risk of certain hereditary cancers based on National Comprehensive Cancer Network (NCCN) criteria.

Acute myocardial infarction in a high-risk cancer population: Outcomes following conservative versus invasive management

BackgroundThe benefits of invasive versus noninvasive management in oncology patients with acute myocardial infarction (AMI) are unclear. We aimed to retrospectively determine outcome differences between conservative and invasive management of AMI in cancer patients. MethodsPatients from our institution between March 2016 and December 2018 with type 1 and type 2 AMI (excluding STEMI) were classified into 2 groups: medical therapy only and invasive strategies. Analyzed outcomes were overall survival (OS), procedural complications, subsequent events, and hospice referral. Kaplan-Meier method and log-rank test were used to compare OS between subgroups. Cox proportional hazards regression analyses were conducted to find factors associated with OS. ResultsWe included 201 patients. Type 1 MI was seen in 152 patients (76%) and type 2 MI in 49 (24%). Median OS was 13 months. Most presented with symptoms other than dyspnea or chest pain (49%) and with ECG revealing changes other than ST-segment depression and T-wave inversion (62%). Patients with type 2 MI had worse OS than patients with type 1 MI (HR = 2.3, p = 0.0002). Early coronary angiography (≤72 h; HR = 0.327, p < 0.0001), late coronary angiography (>72 h; HR = 0.496, p = 0.0426), and percutaneous coronary intervention (HR = 0.481, p = 0.0116) were associated with better OS than noninvasive approaches. Single and dual agent antiplatelet therapy, beta blockers, and statins were each associated with better OS. ConclusionsCancer patients without STEMI who underwent invasive treatment for AMI had better OS compared with those treated only medically, with the highest benefit when coronary angiography was performed within 72 h of admission for AMI.

Selective Targeting of Cancer Stem Cells (CSCs) Based on Photodynamic Therapy (PDT) Penetration Depth Inhibits Colon Polyp Formation in Mice.

Targeting cancer stem cells (CSCs) without damaging normal stem cells could contribute to the development of novel radical cancer therapies. Cells expressing leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) constitute a cancer-causing population in the colon; therefore, targeting of Lgr5+ cells is expected to provide an opportunity to mitigate colon cancer. However, the expression of Lgr5 in normal stem cells makes it difficult to prove the efficacy of therapies targeted exclusively at Lgr5+ cancer cells. We used a modified photodynamic therapy technique involving cellular radiative transfer between green fluorescent protein (GFP)-expressing cells and a rose bengal photosensitizer. After treatment, tumors containing GFP-Lgr5+ cells were observed to be significantly suppressed or retarded with little effect on GFP-Lgr5+ stem cells at the crypt bottom. Lgr5+ CSCs were specifically eradicated in situ, when localized based on the depth from the colon lumen, revealing the potential preventive efficacy of Lgr5-targeted therapy on tumor growth. This study supports the idea that Lgr5+ cells localized near the colon luminal surface are central to colorectal cancer. With further development, the targeting of localized Lgr5+ cancer stem cells, which this study demonstrates in concept, may be feasible for prevention of colon cancer in high-risk populations.

Low-Dose Tamoxifen (LDTam) As a Breast Cancer (BC) Risk-Reduction Strategy in Lymphoma Survivors Exposed to Chest Radiation Therapy (RT) during Adolescence/Young Adulthood - a Randomized, Placebo-Controlled Double Blinded Phase IIb Trial

Background: Lymphoma patients exposed to chest RT during adolescence/young adulthood are at increased risk for BC; the cumulative incidence exceeds 20% by age 45 and the BC risk is comparable to that in women with BRCA1 mutations. These findings present an urgent yet unmet need to reduce the risk of BC in RT-exposed lymphoma survivors. The risk of BC is 50% lower in chest RT-exposed survivors who also receive ovarian radiation, suggesting a critical role of endogenous estrogens in RT-related breast carcinogenesis, making tamoxifen (a selective estrogen receptor modulator) an attractive risk-reducing option. Tamoxifen administered at 20 mg/d is effective in BC prevention in other high risk populations, but severe adverse events (SAE: venous thromboembolism, endometrial cancer) have limited its broad use. Previous biomarker trials in the general population have shown that LDTam (5mg/d) is not inferior to tamoxifen at 20 mg/d in reducing BC risk, and is associated with a safer AE profile. Mammographic breast density (MBD) is an established biomarker of BC risk; high MBD is associated with a 4-fold higher risk of BC. We hypothesized that LDTam would be effective in reducing BC risk (using MBD as a primary endpoint) in chest RT-exposed lymphoma survivors. We used an investigator-initiated, multi-institutional, randomized phase IIb, double blind, placebo controlled trial (FDA IND 107367) to test this hypothesis. Methods: Female patients from 13 sites were ≥25y at enrollment, with a history of exposure to chest RT at ≥12 Gy by age 40 for their primary cancer, and were off therapy for ≥6 mo. Subjects with a prior history of BC/DCIS, B/L mastectomy, or baseline MBD &lt;25% in both breasts were excluded. Tamoxifen 5mg or identical placebo tablets were provided by Sharp Clinical Services (Allentown, PA) under good manufacturing practice. Subjects were randomized 1:1 in a double-blinded fashion by a Web-based system to receive LDTam or placebo daily for 2y. MBD (in both breasts) was measured centrally on digital scans independently by 3 radiologists at baseline, 1y and 2y. Using an intention-to-treat analysis, the efficacy of LDTam in reducing MBD was compared between the LDTam and placebo arms by applying a linear mixed effects model for bivariate normally distributed data with random intercept and time*treatment arm effects. Correlations between the left and right breasts and within radiologists were accounted for in the model. Treating clinicians and all research staff were blinded to the treatment arm. Results: A total of 72 patients (LDTam: n=34; placebo: n=38) participated in the trial; primary diagnosis: Hodgkin lymphoma (86%); non-Hodgkin lymphoma (10%); other (3%); median age at diagnosis of primary cancer: 21.5y (IQR, 16-28), and at trial enrollment: 43.8y (35-49); median time from diagnosis of primary cancer to study: 17.0y (12-26). Median chest RT dose: 30.3 Gy (21-37.3); 11% had received pelvic radiation; 39% were post-menopausal at study. Participant characteristics were comparable between the two treatment arms, as was the mean baseline MBD (LDTam: 52.6% vs. placebo: 50.4%, p=0.6). The time*treatment arm effect was statistically significant (LDTam vs. placebo: estimate = -1.7, SE = 0.5, p = 0.001), indicating a significantly lower mean fitted MBD for LDTam (43.9%) vs. placebo (47.3%) at 2y (Figure). This represented a 16.5% relative reduction in MBD on the LDTam arm, corresponding to an estimated 33% lower risk of BC (assuming that reductions in MBD have the same benefit in lymphoma survivors as they do in the general population). There were no grade 3 or 4 AEs related to LDTam. Grade 2 AEs did not differ between treatment arms (LDTam: 44.1% vs. placebo: 36.8%, p=0.6). There was no difference in the prevalence of moderate-to-severe patient-reported outcomes between the treatment arms (Table). Conclusion: Low-dose tamoxifen was associated with a significantly steeper decline in MBD in chest RT-exposed lymphoma survivors, when compared with placebo, and was safe and well-tolerated. This is the first trial demonstrating efficacy of a pharmacologic intervention in reducing a biomarker strongly associated with breast cancer risk in lymphoma survivors with a past history of chest radiation. Disclosures Palomares: Covance: Other: Medical monitoring. Henderson:Seattle Genetics: Research Funding. OffLabel Disclosure: The drug is a low-dose tamoxifen, a selective estrogen receptor modulator. Tamoxifen in standard doses is used to reduce the risk of breast cancer in high risk populations. Tamoxifen in standard or low doses have not been tested before for chest-irradiated cancer survivors to reduce the risk of radiation-related breast cancer.

The prostate cancer precision screening program: a preliminary report after recruitment of 2 159 men

Objective: The Chinese Anti-Cancer Association Genitourinary Cancer Committee Prostate Cancer Working Group released Consensus of prostate cancer (PCa) screening in 2017. This program aims to evaluate the methods and significance of prostate cancer precision screening in high risk population. Methods: A total of 2 159 eligible males enrolled from 13 community centers and 3 screening centers received PSA test from April 2017 to August 2018. Prostate-specific antigen (PSA) determination in serum with a cut-off of ≥4.0 ng/ml was the main screening test and indication for biopsy. The interviewer-administered questionnaire covered demographic characteristics and environmental exposure factors. The associations between these factors and prostate cancer risk were determined by multivariable unconditional logistic regression models. Results: Altogether, 271 cases (12.6%) had a confirmed PSA increase ≥ 4.0 μg/L (median 9.1, range 4.0-25.0). Subsequently, 57 subjects (21.0%) out of the 271 PSA-suspicious men underwent prostate biopsy, and 34 (59.6%) were confirmed as prostate cancer. Until now, the overall prostate cancer incidence in the first screening round was1.57%. There were no statistical differences in the distributions of PSA-suspicious and prostate cancer incidence between community centers and screening centers (P=0.578 and 0.735). Age (OR: 2.63; 95%CI: 1.84-3.75, P<0.001) and chronic prostatitis history (OR: 2.02; 95%CI: 1.55-2.63, P<0.001) were significantly associated with PSA level. After adjustment for these factors, older age (OR: 4.04; 95%CI: 1.71-9.59, P=0.002) and statins use (OR: 3.09; 95%CI: 1.25-7.69, P=0.015) were associated with an elevated risk of PCa. Conclusions: It is of substantial significance to screen prostate cancer in high risk population. Both community centers and screening centers methods are effective. Although largely underestimated, the incidence of PCa in the targeted Chinese population is higher than expected. Older men have a high risk of harboring PCa. Our study suggests a decreased risk of PCa in men with statins use. Prostate Cancer Precision Screening is promising to improve prostate cancer survival in China.

Grading immunohistochemical markers p16INK4a and HPV E4 identifies productive and transforming lesions caused by low- and high-risk HPV within high-grade anal squamous intraepithelial lesions.

SummaryObjectivesBecause current guidelines recognise high‐grade anal squamous intraepithelial lesions (HSILs) and low‐grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16INK 4a (p16) and E4 in low‐risk human papillomavirus (lrHPV) and high‐risk (hr)HPV‐associated SILs as a potential basis for more selective treatment.MethodsImmunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV‐positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10‐PCR‐DEIA‐LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0–4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0–2) to mark HPV production and life cycle completion.ResultsThere were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade.ConclusionsCombined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a ‘wait and see’ policy for productive HSILs. What's already known about this topic? For preventing anal cancer in high‐risk populations, all patients with high‐grade squamous intraepithelial lesions (HSILs) are treated, even though this group of lesions is heterogeneous, the histology is variable and regression is frequent. What does this study add? By adding human papillomavirus (HPV) E4 immunohistochemistry to p16 INK4a (p16), and grading expression of both markers, different biomarker expression patterns that reflect the heterogeneity of HSILs can be identified.Moreover, p16/E4 staining can separate high‐risk HPV‐associated HSILs into productive and more advanced transforming lesions, providing a potential basis for selective treatment.

117 Gender and Racial Disparities in the Annual Percent Change of Incidence and Mortality Rates of Pancreatic Cancer

INTRODUCTION: In the United States, pancreatic cancer is the fourth leading cause of cancer death for both men and women. The purpose of this study is to investigate the impact of gender, and race/ethnicity on the annual percent change of incidence and mortality rates of pancreatic cancer from 2000–2016 using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients diagnosed with pancreatic cancer from 2000–2016 were identified from the SEER Registry. We retrospectively evaluated gender-specific, and race/ethnicity variations in age-adjusted annual percent changes in incidence rates and mortality rates for people above the age above 20. We used ethnic groups consisting of White, Non-Hispanic White, Black, Asian/Pacific Islander, American Indian/Alaska Native, and Hispanic. RESULTS: Based on the SEER 21 areas data sets, the age-adjusted incidence rates of pancreatic cancer increased from 2000–2014 but remained stable from 2014–2016. The annual percent of change in incidence for both males and females from 2000–2014 was 0.9 and was −1.4 from 2014–2016. Females had an annual percent change of incidence of 0.7 from 2000 to 2016. For males, the annual percent change was 1.2 from 2000–2009 but the annual percent change from 2009–2016 was 0.2. Females had an upward trend of annual percent change of incidence rates during this period. The annual percent change of incidence by race/ethnicity can be seen in Table 1. The annual percent change in mortality rates was analyzed during 2000–2016. Females had an annual percent change of 0.2 and males had an annual percent change of 0.3. The trend of mortality rates was upward for males and females. The annual percent change of mortality rate by race/ethnicity can be seen in Table 2. CONCLUSION: The poor outcome and silent nature of pancreatic cancer necessitates the need to understand the trends associated with disease. Females had an upward trend in the annual percent change of incidence rates of pancreatic cancer from 2000–2016. There is also upward trend for annual percent change of incidence rates for Asians, Hispanics, and Non Hispanic Whites. The trend of annual percent change of mortality rates was increasing for both males and females during 2000–2016. The trend was increasing for both Non-Hispanic White and White Americans. This may support interventions to inform certain race/ethnic populations about the importance of screening for pancreatic cancer in high-risk populations.

Inherited alterations of TGF beta signaling components in Appalachian cervical cancers.

This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. Appalachian women's survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CAREI and CAREII studies (n = 163 invasive cervical cancer cases, 842 controls) were used to assess gene-environment interactions and cancer risk. Polymorphic allele frequencies and socio-behavioral demographic measurements were compared using t tests and χ2 tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. Several alleles demonstrated significant interaction with smoking (TP53 rs1042522, TGFB1 rs1800469), alcohol consumption (NQO1 rs1800566), and sexual intercourse before the age of 18 (TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785). Interestingly, we noted a significant interaction between "Appalachian self-identity" variables and NQO1 rs1800566. Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469/TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469/TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.

Predictive value and clinical significance of increased SSAT-1 activity in healthy adults.

Aim:Spermidine/spermine N1-acetyltransferase (SSAT-1) regulates cell growth, proliferation and death. Amantadine is converted by SSAT-1 to acetylamantadine (AA). In our earlier studies, although SSAT-1 was activated in patients with cancer, a number of ostensibly healthy adult volunteers had higher than expected AA concentration. This study was therefore undertaken to examine the outlier group.Materials & methods:A follow up of urine analysis for AA by liquid chromatography-tandem mass spectrometry as well as clinical assessments and additional blood analyses were conducted.Results:In some of the outlier controls, higher than expected AA concentration was linked to increased serum carcinoembryonic antigen. Clinical and radiographic assessments revealed underlying abnormalities in other cases that could represent premalignant conditions. Hematology tests revealed elevations in white blood cells and platelets, which are markers of inflammation.Conclusion:High urine concentration of AA could be used as a simple and useful test for screening of cancer in high-risk populations.