Biomedical subjects

Hoda Anton-Culver

Publications and source records attributed to Hoda Anton-Culver.

At least 19 recordsLinked to original sources

PubMed2022

Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence.

Accurate, highly specific immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to evaluate seroprevalence. This study investigated the concordance of results across four immunoassays targeting different antigens for sera collected at the beginning of the SARS-CoV-2 pandemic in the United States. Specimens from All of Us participants contributed between January and March 2020 were tested using the Abbott Architect SARS-CoV-2 IgG (immunoglobulin G) assay (Abbott) and the EuroImmun SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) (EI). Participants with discordant results, participants with concordant positive results, and a subset of concordant negative results by Abbott and EI were also tested using the Roche Elecsys anti-SARS-CoV-2 (IgG) test (Roche) and the Ortho-Clinical Diagnostics Vitros anti-SARS-CoV-2 IgG test (Ortho). The agreement and 95% confidence intervals were estimated for paired assay combinations. SARS-CoV-2 antibody concentrations were quantified for specimens with at least two positive results across four immunoassays. Among the 24,079 participants, the percent agreement for the Abbott and EI assays was 98.8% (95% confidence interval, 98.7%, 99%). Of the 490 participants who were also tested by Ortho and Roche, the probability-weighted percentage of agreement (95% confidence interval) between Ortho and Roche was 98.4% (97.9%, 98.9%), that between EI and Ortho was 98.5% (92.9%, 99.9%), that between Abbott and Roche was 98.9% (90.3%, 100.0%), that between EI and Roche was 98.9% (98.6%, 100.0%), and that between Abbott and Ortho was 98.4% (91.2%, 100.0%). Among the 32 participants who were positive by at least 2 immunoassays, 21 had quantifiable anti-SARS-CoV-2 antibody concentrations by research assays. The results across immunoassays revealed concordance during a period of low prevalence. However, the frequency of false positivity during a period of low prevalence supports the use of two sequentially performed tests for unvaccinated individuals who are seropositive by the first test. IMPORTANCE What is the agreement of commercial SARS-CoV-2 immunoglobulin G (IgG) assays during a time of low coronavirus disease 2019 (COVID-19) prevalence and no vaccine availability? Serological tests produced concordant results in a time of low SARS-CoV-2 prevalence and no vaccine availability, driven largely by the proportion of samples that were negative by two immunoassays. The CDC recommends two sequential tests for positivity for future pandemic preparedness. In a subset analysis, quantified antinucleocapsid and antispike SARS-CoV-2 IgG antibodies do not suggest the need to specify the antigen targets of the sequential assays in the CDC's recommendation because false positivity varied as much between assays targeting the same antigen as it did between assays targeting different antigens.

Humans↗

PubMed2016

Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study.

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression.

Adult↗

PubMed2007

Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival.

Elevated polyamine and nitric oxide levels (both derived from arginine) promote tumorigenesis, whereas non-steroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal cancer (CRC) incidence in experimental and epidemiologic studies. We investigated dietary arginine-induced intestinal tumorigenesis and NSAID-inhibitory effects in Apc(Min/+) mice differentially expressing nitric oxide synthase-2 (Nos2). We also studied effects of estimated arginine exposures through meat consumption on tumor characteristics and survival in human CRC cases. Dietary arginine increased high-grade colon adenoma incidence in Apc(Min/+)Nos2(+/+) mice, but not in Nos2 knockout mice. Additionally, celecoxib suppressed intestinal steady state ornithine decarboxylase RNA levels (p < 0.001), induced steady state spermidine/spermine N(1)-acetyltransferase RNA levels (p = 0.002), decreased putrescine levels (p = 0.04) and decreased tumor number in the small intestines of Apc(Min/+)Nos2(+/+) mice (p = 0.0003). Five hundred and eleven cases from our NCI-supported CRC gene-environment study were analyzed based on self-reported meat (as a surrogate for arginine) consumption. Familial CRC cases (n = 144) in the highest meat consumption quartile (Q4) had no statistically significant differences in tumor grade compared to cases in Q1-Q3 (p = 0.32); however, they were observed to have decreased overall survival (OS) (10-year OS = 42% vs. 65%; p = 0.017), and increased risk of death in an adjusted analysis (hazards ratio [HR] = 2.24; p = 0.007). No differences in tumor grade, OS or adjusted HR were observed for sporadic CRC cases (n = 367) based on meat consumption. Our results suggest important roles for arginine and meat consumption in CRC pathogenesis, and have implications for CRC prevention.

Acetyltransferases↗

PubMed2006

Malignancies following in situ cervical cancer in Hispanic Americans and non-Hispanic Whites.

OBJECTIVES: Some risk factors for cervical cancer in situ convey risk for malignancies of the cervix and other sites. We estimate risk of several malignancies following in situ cancer of the cervix for Hispanic Americans and non-Hispanic Whites. METHODS: Using California Cancer Registry data (1988-1999) we identify 56,020 women with cervical cancer in situ and observe subsequent malignancies in that cohort, with over three million woman-months of follow-up. We focus on cancers of the reproductive system and cancers related to smoking. Risk estimates are standardized incidence ratios, accounting for age, time at risk, cancer type, and race/ethnicity. RESULTS: There is elevated risk for invasive cervical cancer (SIR=4.1, 95% CI: 3.5-4.7), which is significantly higher for Hispanics than for non-Hispanic Whites (SIRs=5.2 and 3.2, respectively, chi2(1)=7.66, P=0.006). Excluding cervix, non-Hispanic Whites show elevated risk for a pool of reproductive cancers (SIR=1.8, 95% CI: 1.4-2.4). While both groups show elevated risk for a pool of smoking-related cancers, only non-Hispanic Whites show significant risk specifically for lung cancer (SIR=1.7, 95% CI: 1.4-2.1). Non-Hispanic Whites show elevated risk for ovarian cancer (SIR=1.8, 95% CI: 1.3-2.4). Ovarian cancer following in situ cervical cancer is disproportionately of borderline histology (G2(1)=7.43, P=0.006). CONCLUSIONS: These results have implications for public health planning for women, as well as better understanding of disparities in care or biologic paths to malignancies in women with in situ cancer of the cervix.

Adult↗

PubMed2006

Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer.

INTRODUCTION: There is growing evidence that heritable genetic variation modulates metastatic efficiency. Our previous work using a mouse mammary tumor model has shown that metastatic efficiency is modulated by the GTPase-activating protein encoded by Sipa1 ('signal-induced proliferation-associated gene 1'). The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) within the human SIPA1 gene are associated with metastasis and other disease characteristics in breast cancer. METHOD: The study population (n = 300) consisted of randomly selected non-Hispanic Caucasian breast cancer patients identified from a larger population-based series. Genomic DNA was extracted from peripheral leukocytes. Three previously described SNPs within SIPA1 (one within the promoter [-313G>A] and two exonic [545C>T and 2760G>A]) were characterized using SNP-specific PCR. RESULTS: The variant 2760G>A and the -313G>A allele were associated with lymph node involvement (P = 0.0062 and P = 0.0083, respectively), and the variant 545C>T was associated with estrogen receptor negative tumors (P = 0.0012) and with progesterone negative tumors (P = 0.0339). Associations were identified between haplotypes defined by the three SNPs and disease progression. Haplotype 3 defined by variants -313G>A and 2760G>A was associated with positive lymph node involvement (P = 0.0051), and haplotype 4 defined by variant 545C>T was associated with estrogen receptor and progesterone receptor negative status (P = 0.0053 and P = 0.0199, respectively). CONCLUSION: Our findings imply that SIPA1 germline polymorphisms are associated with aggressive disease behavior in the cohort examined. If these results hold true in other populations, then knowledge of SIPA1 SNP genotypes could potentially enhance current staging protocols.

Abortion, Spontaneous↗

PubMed2006

Changes in acquired immunodeficiency syndrome-related non-Hodgkin lymphoma in the era of highly active antiretroviral therapy: incidence, presentation, treatment, and survival.

BACKGROUND: The authors sought to determine whether the availability of highly active antiretroviral therapy (HAART) coincided with changes in the epidemiology of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). METHODS: Cancer registry data from 1988-2000 were linked with AIDS registry data from 1981 to July 2003 for San Diego County to identify 537 AIDS-NHL patients. By using the total number of patients with AIDS who were alive as of July 1 annually as the AIDS population denominator, the average annual incidence of NHL was estimated among patients with AIDS for the pre-HAART period (1988-1995) and post-HAART period (1996-2000). The chi-square test was used to compare proportions, and a Cox proportional hazards model was used to compare survival between the pre-HAART and post-HAART periods. RESULTS: The incidence of NHL decreased from 29.6 per 1000 person-years pre-HAART to 6.5 per 1000 person-years post-HAART. The proportion of patients who had NHL of central nervous system (CNS) origin decreased from 28% pre-HAART to 17% post-HAART. Among patients with systemic NHL, 54% received chemotherapy pre-HAART, and 72% received chemotherapy post-HAART. The percentage of intermediate-grade NHL increased from 33% pre-HAART to 49% post-HAART, and the percentage of high-grade NHL decreased from 38% to 19%, respectively. A diagnosis of human immunodeficiency virus infection preceding the NHL diagnosis and Stage IV NHL were associated with worse survival, whereas a diagnosis of NHL in the post-HAART period and chemotherapy were associated with better survival. The median survival was 4 months pre-HAART and 9 months post-HAART. CONCLUSIONS: Since the introduction of HAART, there has been a decrease in the incidence of systemic and CNS NHL among patients with AIDS. Among patients with systemic, AIDS-related NHL, there has been decreased high-grade histology, increased use of chemotherapy, and improved survival.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Improved survival and chemotherapy response among patients with AIDS-related non-Hodgkin's lymphoma receiving highly active antiretroviral therapy.

Highly active antiretroviral therapy (HAART) became available in the US in 1996. Using the population-based cancer registry, we identified 233 patients with AIDS-related systemic NHL diagnosed in San Diego or Orange County in 1994-1999, of whom 137 were diagnosed 1996-1999. We performed Kaplan-Meier analyses to compare survival between patients who received HAART at NHL diagnosis or thereafter versus untreated patients and Cox proportional hazard models for adjusted survival. We used logistic regression to determine if concomitant HAART changed the probability of complete response to chemotherapy and the Mann-Whitney U-test to compare the median number of chemotherapy cycles between patients who received HAART during chemotherapy versus those who did not. Among patients diagnosed with NHL in 1996-1999, 40 (29%) were taking HAART at NHL diagnosis. The median survival was three months among patients who did not receive HAART versus 16 months among HAART-treated patients. HAART, chemotherapy, high performance status, and NHL stage < IV were associated with improved survival. Concomitant HAART, completion of > or = 6 chemotherapy cycles, and NHL stage < IV were associated with complete response to chemotherapy. The median number of chemotherapy cycles was five among patients who received HAART concomitant with chemotherapy versus three among untreated patients. We conclude that HAART should be initiated or continued after NHL diagnosis, including during the period of chemotherapy administration.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Presentation and outcomes of systemic non-Hodgkin's lymphoma: a comparison between patients with acquired immunodeficiency syndrome (AIDS) treated with highly active antiretroviral therapy and patients without AIDS.

We used the San Diego/Orange County cancer registry to identify 64 cases of systemic non-Hodgkin's lymphoma (NHL) with AIDS who received highly active antiretroviral therapy (HAART) at the time of NHL diagnosis or thereafter and 64 NHL controls without AIDS, matched on age, sex, race, time of NHL diagnosis (1994-1995 and 1996-1999), and hospital type (academic, large community, and small community). We compared cases and controls by chi-squared tests and Kaplan-Meier methods. Thirty-three percent of cases had high grade histology versus 11% of controls (p < 0.01); 69% had baseline hemoglobin <13 g/dL versus 35% controls (p < 0.001) and 21% had baseline neutrophils <2,000/mcl versus 4% of controls (p < 0.001). Overall median survival was 16 months for cases versus 99 months for controls (p < 0.01). Among 40 matched pairs of cases and controls who received chemotherapy, 32% of cases received reduced-dose chemotherapy versus 5% of controls (p < 0.01) and median survival was 33 months for cases and 99 months for controls (p < 0.44). Patients with AIDS-related NHL who received HAART had high grade histology and baseline cytopenia and received reduced-dose chemotherapy more often than patients without AIDS. However, AIDS patients who received HAART and chemotherapy had survival similar to NHL patients without AIDS, an improvement from the pre-HAART era. Appropriate hematologic support, through growth factors, transfusions, and avoidance of drugs with hematologic toxicity, might allow full dosing of chemotherapy, and perhaps would further improve outcomes among patients with AIDS and NHL.

Acquired Immunodeficiency Syndrome↗

PubMed2006

The prevalence of CDKN2A germ-line mutations and relative risk for cutaneous malignant melanoma: an international population-based study.

Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which "cases" have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and "controls" have incident first primary melanoma [single primary melanoma (SPM)]. Participants were ascertained from nine geographic regions in Australia, Canada, Italy, and United States. In the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for analysis, the relative risk of a subsequent melanoma among patients with functional mutations who have an existing diagnosis of melanoma, after adjustments for age, sex, center, and known phenotypic risk factors, is estimated to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly depending on the type of mutation involved. The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma.

Aged↗

PubMed2006

Analysis of co-aggregation of cancer based on registry data.

OBJECTIVE: An exploratory analysis of co-aggregation of cancers using registry-based data. METHODS: We utilized sibships from over 18,000 families who had been recruited to the NCI-sponsored multi-institutional Cancer Genetics Network. The analysis assesses co-aggregation at the individual and family level and adjusts for ascertainment. RESULTS: We found statistically significant familial co-aggregation of lung cancer with pancreatic (adjusted p < 0.001), prostate (adjusted p < 0.003), and colorectal cancers (adjusted p = 0.004). In addition, we found significant familial co-aggregation of pancreatic and colorectal cancers (adjusted p = 0.018), and co-aggregation of hematopoietic and (non-ovarian) gynecologic cancers (adjusted p = 0.01). CONCLUSION: This analysis identified familial aggregation of cancers for which a genetic component has yet to be established.

Female↗

PubMed2006

Dietary fat, fiber, vegetable, and micronutrients are associated with overall survival in postmenopausal women diagnosed with breast cancer.

Relatively few studies have assessed the relationship between dietary intakes and survival after breast cancer diagnosis. We investigated the influence of diet, including dietary fat (percentage energy), fiber, vegetable, and fruit intakes, and micronutrients (folate, carotenoids, and vitamin C) on overall survival in women diagnosed with breast cancer. Subjects were postmenopausal women diagnosed with breast cancer (N = 516) between 1994 and 1995 with a mean survival time of 80 mo (SD: 18). Subjects completed a food frequency questionnaire for the year prior to diagnosis. Cox proportional hazards models were used to measure the relationship between dietary intakes and death due to any cause after breast cancer diagnosis. In the multivariate analysis, we found that the hazard ratio [HR and 95% confidence interval (CI)] of dying in the highest tertile compared to the lowest tertile of total fat, fiber, vegetable, and fruit was 3.12 (95% CI = 1.79-5.44), 0.48 (95% CI = 0.27-0.86), 0.57 (95% CI = 0.35-0.94), and 0.63 (95% CI = 0.38-1.05), respectively (P <or= 0.05 for trend, except for fruit intake). Other nutrients including folate, vitamin C, and carotenoid intakes were also significantly associated with reduced mortality (P <or= 0.05 for trend). These results suggest that in postmenopausal women diagnosed with breast cancer, reduced dietary fat and increased fiber, vegetable, fruit, and other nutrient intakes associated with a plant-based, high-fiber diet improves overall survival after breast cancer diagnosis.

Body Mass Index↗

PubMed2006

Highly active antiretroviral therapy is associated with improved survival among patients with AIDS-related primary central nervous system non-Hodgkin's lymphoma.

Highly active retroviral therapy (HAART) has been in widespread use in the United States since 1996. We sought to determine how the use of HAART influenced survival among patients with acquired immunodeficiency syndrome (AIDS) and primary central nervous system (CNS) non-Hodgkin's lymphoma (NHL). We used the population-based San Diego and Orange County cancer registry to identify 94 patients with both AIDS and CNS NHL diagnosed 1994-1999, of whom 31 were diagnosed 1996-1999. We performed Kaplan-Meier analyses to compare survival between patients who received HAART at NHL diagnosis or thereafter versus untreated patients and Cox proportional hazard models for adjusted survival. Among the patients diagnosed with NHL in 1996-1999, seven (23%) were taking HAART at the time of NHL diagnosis. Median survival was eight months for those who received HAART at the time of lymphoma diagnosis or after, versus one month for untreated patients. HAART, radiation therapy, and better performance status were associated with improved survival. We conclude that HAART prolongs survival in AIDS-related CNS NHL.

Adult↗

PubMed2006

Gender and race/ethnicity affect the cost-effectiveness of colorectal cancer screening.

BACKGROUND AND AIMS: Colorectal cancer screening beginning at age 50 is recommended for all Americans considered at average risk for the development of colorectal cancer regardless of gender or race/ethnicity. We determined the influence of gender and race/ethnicity on the cost-effectiveness of recommended colorectal cancer screening regimens. METHODS: We determined age-specific colorectal cancer incidence rates; the proportion of left-sided cancers; and the proportion of localized cancers in Asian, black, Latino and white men and women using the California Cancer Registry. We incorporated these data and available data for life expectancy and colorectal cancer survival to model the cost-effectiveness of two 35-year colorectal cancer-screening interventions. RESULTS: Age-specific colorectal cancer incidence rates were highest in black men and lowest in Latino women. Screening beginning at age 50 was most cost-effective in black men and least cost-effective in Latino women (measured as dollars spent per year of life saved) using annual fecal occult blood testing combined with flexible sigmoidoscopy every five years and using colonoscopy every 10 years. The cost-effectiveness of a 35-year screening program in black men beginning at age 45 was similar to the cost-effectiveness of screening white men and black women beginning at age 50 and more cost-effective than screening nonblack women as well as Asian and Latino men beginning at age 50. CONCLUSIONS: Screening is most cost-effective in black men because of high age-specific colorectal cancer incidence rates. Initiation of colorectal cancer screening in this high-risk group prior to age 50 should be strongly considered.

Aged↗

PubMed2005

Epidemiology of bronchioloalveolar carcinoma: improvement in survival after release of the 1999 WHO classification of lung tumors.

PURPOSE: Classification changes for bronchioloalveolar carcinoma (BAC) by the WHO in May 1999 narrowed its definition. This study was undertaken in an attempt to characterize the impact of these changes on the epidemiology of BAC. PATIENTS AND METHODS: This retrospective study involves data analysis from the population-based Cancer Surveillance Programs of three Southern California counties from 1995 to 2003. BAC cases diagnosed after May 1999 are compared with BAC cases before that time by clinicopathologic variables including survival. RESULTS: Incident cases (11,969) of non-small-cell lung cancer (NSCLC) were analyzed, including 626 cases of BAC (5.2%). Median overall survival (OS) for BAC patients diagnosed after May 1999 (> 53 months) was significantly improved over median OS for BAC patients before May 1999 (32 months; P = .012). This survival benefit remained after adjustment for sex, smoking status, and stage at presentation (hazard ratio for time of diagnosis before May 1999 compared with a diagnosis after May 1999 = 1.43; P = .015). Median OS for non-BAC NSCLC patients diagnosed before May 1999 (9 months) did not differ from the median OS of such patients afterwards (10 months; P = .09). CONCLUSION: This epidemiologic study is the first to demonstrate a survival advantage for BAC patients diagnosed after May 1999 compared with BAC patients diagnosed before this time-a finding that persists after adjustment for sex, smoking status, and stage at presentation. We believe that this observed survival benefit likely reflects changes in the revised 1999 WHO classification.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2005

Feasibility of management of high-grade cervical lesions in a single visit: a randomized controlled trial.

CONTEXT: The incidence of cervical cancer is higher among low-income and minority women who have never undergone a conventional Papanicolaou test or who do not follow up after testing. Screening has been shown to reduce cervical cancer incidence rates. OBJECTIVES: To determine the feasibility and acceptability of immediately treating women with severely abnormal Papanicolaou test results by using a single-visit cervical cancer screening and treatment program and to compare treatment rates and 12-month follow-up rates with those of women who received usual care. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted among 3521 women aged 18 years or older recruited between January 1999 and April 2002 at US community health centers located in predominantly Latino underserved areas. INTERVENTIONS: Women randomized to usual care (n = 1805) were discharged immediately after examination. Women randomized to the single-visit group (n = 1716) remained at the clinic until the results of their conventional Papanicolaou test were available. Large loop electrosurgical excision procedure was performed in single-visit patients with either a diagnosis of a high-grade squamous intraepithelial lesion (HGSIL)/atypical glandular cells of undetermined significance (AGUS) or suspicion of carcinoma. All other patients with abnormal Papanicolaou test results were referred to abnormal cytology clinics or elected to receive follow-up care outside the study's medical system. MAIN OUTCOME MEASURES: Treatment rates for HGSIL/AGUS at 6 months, follow-up rates at 6 months for lower-grade lesions, and 1-year follow-up rates for all patients. RESULTS: The rate of abnormal Papanicolaou test results was 4.1%. One percent of results showed high-grade lesions. In the single-visit group, the mean visit time was 2.8 hours and the mean time for delivery and processing of the Papanicolaou tests was 66 minutes. Six months after randomization, 14 (88%) of 16 single-visit and 10 (53%) of 19 usual care patients with HGSIL/AGUS had completed treatment. Fifty percent in the single-visit program and 53% of usual care with less abnormal Papanicolaou tests completed treatment within 6 months. Overall, 36% in each group presented for a follow-up Papanicolaou test 1 year later. Women in the single-visit group with high-grade lesions (10/16; 63%) were significantly more likely to attend follow-up for Papanicolaou tests 12 months later than women with similar lesions in the usual care group (4/19; 21%). CONCLUSIONS: For cervical cancer screening, the single-visit program was feasible and the degree of acceptability was high in this underserved population. Single visit programs provide an opportunity to increase the rate of immediate treatment and follow-up of women with severely abnormal Papanicolaou test results. This strategy did not improve follow-up rates for women with less-abnormal results. Trial Registration http://ClinicalTrials.govIdentifier: NCT00237562.

Adult↗

PubMed2005

Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample.

BACKGROUND: Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58% in Europe to 91% in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma. METHODS: Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53% participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1alpha, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin-cohort method. RESULTS: The risk of melanoma in CDKN2A mutation carriers was approximately 14% (95% CI = 8% to 22%) by age 50 years, 24% (95% CI = 15% to 34%) by age 70 years, and 28% (95% CI = 18% to 40%) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. CONCLUSIONS: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.

Adult↗

PubMed2005

Meeting report: NCI think tanks in cancer biology.

Over the past year and a half, the Division of Cancer Biology of NCI has been assessing the state of cancer biology, with the goal of developing a research agenda for the near future that would accelerate progress in cancer research. Our goal was to identify emerging concepts and promising opportunities for investigation across nine scientific areas with unusual promise for rapid progress. A series of meetings called Think Tanks was convened, each involving a panel of 15-25 experts. In all, over 160 leaders in cancer research and related fields discussed the current state of science in their disciplines, projected its trajectory and recommended what NCI could or should do to facilitate progress. In addition to emphasizing the importance of continued support for investigator-initiated research, the Think Tanks permitted identification of a number of overarching themes. Critical among them was the need to support the development of integrative cancer biology and to encourage studies of the tumor microenvironment by establishing an infrastructure for interactive research. There was also consensus about the importance of comparative studies of normal and tumor states, and development of mechanisms for supporting collaborative, interdisciplinary research and training.

Animals↗

PubMed2005

Dynamical interactions between multiple cancers.

Multiple tumors in a patient have the possibility to interact with each other, through the competition for new blood supply which is required for growth and progression (angiogenesis). The multiple tumors can be independent, multiple primary cancers. Alternatively, they can be metastases which originate from one primary tumor. This paper uses mathematical models to investigate such dynamical interactions between multiple cancers. We start with a model which describes the growth of a single angiogenic tumor, and then generalize this model to include multiple tumors which compete for circulating endothelial progenitor cells in order to build new blood vessels. We explore under which conditions multiple tumors can coexist, and when one tumor can exclude other tumors from growing. Based on this framework, we discuss the circumstances under which independent multiple primary tumors can arise. We further discuss the inefficiency of metastatic cells to grow successfully, and suggest an explanation for the occurrence of multiple metastases with an unknown primary cancer.

Humans↗