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1.
Curr Eye Res ; : 1-8, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33445973

RESUMO

PURPOSE: To evaluate whether principal component analysis (PCA) can assess various diagnostic tests of dry eye disease (DED), providing a simplified, more informative measure of disease status than individual clinical test parameters (ICTP). MATERIALS AND METHODS: ICTP were analyzed using PCA in two groups of normal rabbits (Groups 1 and 2). Group 3, not truly normal, was also assessed. DED was induced in Group 1 by complete dacryoadenectomy; in Groups 2 and 3 by injection of concanavalin A. Tear break up time, tear osmolarity, Schirmer's tear test and rose bengal staining were the ICTP measured in all groups. Statistical analysis including descriptive statistics, t test, correlation coefficients and PCA was done. PCA using ICTP data from Group 1 generated axes; Group 2 and 3 were plotted over these axes. RESULTS: All groups had induction of DED. Correlations for all ICTP were in the correct direction and were strongest for Group 1 and weakest in Group 3. PCA clearly separated DED and normal eyes. Principal component (PC) 1, made up of nearly equal contributions from the four clinical tests, explained 73% of the variation and provided a means to separate normal from DED. PC 1 values under 0.52 can be mathematically defined as DED. Of all pairwise comparisons, PC 1 vs PC 2 and PC 1 vs PC 3 were the most informative providing excellent spatial separation and additional information regarding DED status. CONCLUSIONS: PCA proved useful for evaluating DED providing a simpler, more comprehensive assessment than ICTP. PC 1 is a valuable, clinically relevant, and informative metric for DED status and severity having superior diagnostic value and statistical strength compared to ICTP. Spatial information on biplots of PC 1 vs PC 3 is also informative. PCA, and specifically PC 1, has the potential to serve as a biomarker for DED.

2.
Lung ; 198(6): 967-972, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33159560

RESUMO

INTRODUCTION: Lung cancer is the leading cause of cancer death in the USA, claiming more than 140,000 deaths annually. Delays in diagnosis and treatment can lead to missed opportunities for both curative and life prolonging therapies. This study aimed to evaluate duration of time to diagnosis and first treatment, as well as investigate reasons for delays in care. METHODS: This retrospective study included all lung cancer cases diagnosed by Stony Brook's Lung Cancer Evaluation Center (LCEC) between 2013 and 2019. Demographic, radiologic, pathologic and clinical variables were investigated, including cancer staging, histology, and medical and family histories. Evaluations included the determination of median time from initial encounter to diagnosis, median time from diagnosis to start of treatment and an exploration of the factors that influence possible causes for delays in care. RESULTS: The LCEC's comprehensive multidisciplinary lung nodule program yielded a median length of time from CT to PET of 11 days, PET to procedure of 13 days, procedure to treatment consult of 9 days, and from consult to treatment of 9 days. LCEC patients experienced an overall median of 44 days from initial presentation to first treatment compared to the national ideal of 62 days, thereby representing a 29% reduction in time from first CT to onset of treatment. CONCLUSION: Delays in lung cancer diagnosis and treatment can negatively impact patient morbidity and mortality. This study suggests that a coordinated multidisciplinary lung cancer program may reduce delays in care, thereby improving patient outcomes.

3.
J Nurse Pract ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33250671

RESUMO

Background: According to the Centers for Disease Control and Prevention, COVID-19 has affected more than 5,119,711 patients with more than 163,651 confirmed deaths reported. The mass media coverage and widespread eruption of illnesses have been associated with adverse mental health outcomes.1 Cancer patients represent an already-compromised population with elevated levels of anxiety and distress; the introduction of the COVID-19 pandemic places this vulnerable group at an even higher risk for mental health consequences. The purpose of this quality improvement initiative was to identify lung cancer patients in our care who demonstrated increased levels of anxiety and distress directly related to the COVID-19 pandemic and to facilitate the acquisition of appropriate care to address their mental health needs. This initiative was designed to aid in the reduction of stress and anxiety in an already burdened population. Methods: The sample included 441 patients undergoing treatment for or surveillance of lung cancer who were screened from April 2020 to July 2020 through the Lung Cancer Evaluation Center. Using the National Comprehensive Cancer Network (NCCN) Distress Thermometer, patients were called and asked a series of questions regarding their distress levels in relation to the COVID-19 pandemic. The NCCN tool uses a numeric scale from 0 to 10 to quantify level of distress, with 0 representing no distress and 10 indicating severe distress. Any patient scoring a 6 or greater was referred to the cancer center social worker. The social worker evaluated the patients' needs and formulated a plan. Any patient who reported a distress level between 3 and 5 was counseled by the nurse practitioner to evaluate further needs. Patients reported reasons for distress as fear of delayed testing, contracting the virus, and changes in their lifestyle (not seeing family, isolation, etc.). Results: We found that screening all patients during the pandemic yielded a higher than normal percentage of individuals who were in need of some level of mental health services. Cancer patients, particularly lung cancer patients, have increased fear due to the respiratory symptoms of COVID-19. After completion of this quality improvement initiative, we have incorporated distress assessment and triage protocols into our practice for all patients. Importance and Implications: Patients with underlying medical conditions including cancer know that they are at increased risk of complications from the COVID-19 virus. This may cause them increased anxiety, distress, and fear. Screening this population with phone calls can effectively identify patients at risk, and with the implementation of this initiative, we can ensure that those who feel isolated or experience heightened levels of distress receive the appropriate care they need.

4.
Cancer Epidemiol ; 68: 101804, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32896806

RESUMO

BACKGROUND: Longitudinal data are limited regarding the impact of a multidisciplinary team (MDT) approach on patient outcomes among those diagnosed with lung cancer. The purpose of this study is to 1) compare 1- and 3-year recurrence and mortality rates among patients receiving a MDT vs. standard model of care; and 2) assess trends in these proportions over a 10-year period. METHODS: This investigation included 2044 lung cancer cases reported to the Stony Brook Cancer Registry between 2006 and 2015. Patients were stratified into 2 groups, those participating in Stony Brook's Lung Cancer Evaluation Center's (LCEC) MDT Program (n = 1179) and those receiving a standard model of care (n = 865). 1- and 3-year stage-stratified recurrence and mortality rates are reported. Logistic regression analyses are performed and linear by linear associations are used to assess trends over time. RESULTS: A higher proportion of patients in the MDT program (LCEC) remained disease-free at 1-year compared those receiving standard care (80.0 % vs 62.3 %, p < 0.01). There were no significant changes in mortality over the 10-year observation period in either group, however the rates were significantly lower among LCEC vs non-LCEC cases after adjusting for possible confounders (OR = 0.68 (0.51,0.90) at 1-year; OR = 0.50 (0.36, 0.70) at 3-years). Recurrence was also lower at 3-years in the MDT group (OR = 0.51 (0.32, 0.79)). CONCLUSIONS: This study suggests that a comprehensive MDT program for lung cancer yields improved patient outcomes compared to the standard model of care and this approach may help to decrease rates of disease recurrence and mortality.

5.
Cancer Manag Res ; 12: 7165-7171, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848470

RESUMO

Background: The purpose of this study was to determine which factors predicted survival and to derive a risk prediction model for patients with locally advanced non-small cell lung cancer (NSCLC) receiving concurrent chemo-radiotherapy (cCRT). Methods: This investigation included 149 patients with locally advanced NSCLC who were treated with cCRT at Stony Brook University Hospital between 2007 and 2015. A finite set of demographic, clinical, and treatment variables were evaluated as independent prognostic factors. Kaplan-Meier survival curves were generated, and log rank tests were used to evaluate difference in survival between groups. To derive a risk score for mortality, a machine learning approach was utilized. To maximize statistical power while examining replicability, the sample was split into discovery (n=99) and replication (n=50) subsamples. Elastic-net regression was used to identify a linear prediction model. Youden's index was used to identify appropriate cutoffs. Cox proportional hazards regression was used to examine mortality risk; model concordance and hazards ratios were reported. Results: One-quarter of the patients survived for three years after initiation of cCRT. Prognostic factors for survival in the discovery group included age, sex, smoking status, albumin, histology, largest tumor size, number of nodal stations, stage, induction therapy, and radiation dose. The derived model had good risk predictive accuracy (C=0.70). Median survival time was shorter in the high-risk group (0.93 years) vs the low-risk group (2.40 years). Similar findings were noted in the replication sample with strong model accuracy (C=0.69) and median survival time of 0.93 years and 2.03 years for the high- and low-risk groups, respectively. Conclusion: This novel risk prediction model for overall survival in patients with stage III NSCLC highlights the importance of integrating patient, clinical, and treatment variables for accurately predicting outcomes. Clinicians can use this tool to make personalized treatment decisions for patients with locally advanced NSCLC treated with concurrent chemo-radiation.

6.
Eur Urol ; 78(3): 316-320, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32409115

RESUMO

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.

7.
Blood Adv ; 4(1): 181-190, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935283

RESUMO

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

8.
Cancer Prev Res (Phila) ; 12(7): 463-470, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31248853

RESUMO

This prospective investigation derived a prediction model for identifying risk of incident lung cancer among patients with visible lung nodules identified on computed tomography (CT). Among 2,924 eligible patients referred for evaluation of a pulmonary nodule to the Stony Brook Lung Cancer Evaluation Center between January 1, 2002 and December 31, 2015, 171 developed incident lung cancer during the observation period. Cox proportional hazard models were used to model time until disease onset. The sample was randomly divided into discovery (n = 1,469) and replication (n = 1,455) samples. In the replication sample, concordance was computed to indicate predictive accuracy and risk scores were calculated using the linear predictions. Youden index was used to identify high-risk versus low-risk patients and cumulative lung cancer incidence was examined for high-risk and low-risk groups. Multivariable analyses identified a combination of clinical and radiologic predictors for incident lung cancer including ln-age, ln-pack-years smoking, a history of cancer, chronic obstructive pulmonary disease, and several radiologic markers including spiculation, ground glass opacity, and nodule size. The final model reliably detected patients who developed lung cancer in the replication sample (C = 0.86, sensitivity/specificity = 0.73/0.81). Cumulative incidence of lung cancer was elevated in high-risk versus low-risk groups [HR = 14.34; 95% confidence interval (CI), 8.17-25.18]. Quantification of reliable risk scores has high clinical utility, enabling physicians to better stratify treatment protocols to manage patient care. The final model is among the first tools developed to predict incident lung cancer in patients presenting with a concerning pulmonary nodule.


Assuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Modelos Estatísticos , Nódulo Pulmonar Solitário/fisiopatologia , Idoso , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Prognóstico , Curva ROC , Fumar/efeitos adversos
9.
Lung Cancer (Auckl) ; 9: 65-71, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30197547

RESUMO

Background: Lobectomy has traditionally been recommended for fit patients diagnosed with early-stage non-small-cell lung cancer (NSCLC). Recently, however, stereotactic body radiotherapy (SBRT) has been introduced as an alternative treatment option. The purpose of this investigation is to compare survival outcomes for individuals with stage I/II NSCLC treated with lobectomy vs SBRT. Methods: This retrospective study included 191 patients (100 surgery, 91 SBRT) identified through the Lung Cancer Evaluation Center, Stony Brook, NY, between 2008 and 2012. Survival and recurrence rates were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models to adjust for possible confounders. A subset of cases was propensity-matched to address potential differences in health status between groups. Results: 1-, 3-, and 5-year survival outcomes were significantly better among patients undergoing lobectomy vs SBRT. Survival rates at 3 years were 92.8% and 59.0% (p<0.001) in the 2 groups, respectively. Propensity-matched analyses indicated similar findings. Recurrence rates were likewise lower among patients undergoing surgery (7.1% vs 21.0%, p<0.01 at 3 years); however, statistical significance was not maintained in the propensity-matched analysis. Conclusion: These findings add to a growing evidence base supporting the use of lobectomy vs SBRT in the treatment of lung cancer among healthy, early-stage NSCLC patients.

10.
Mol Carcinog ; 57(10): 1311-1318, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29873413

RESUMO

Gene expression changes within the Hippo pathway were found to be associated with large tumor size and metastasis in breast cancer. The combined effect of genetic variants in genes of this pathway may have a causal role in breast cancer development. We examined 7086 SNPs that were not highly correlated (r2 < 0.8) in 35 Hippo pathway genes using data from the genome-wide association study of breast cancer from the Root Consortium, which includes 3686 participants of African ancestry from Nigeria, United States of America, and Barbados: 1657 cases (403 estrogen receptor-positive [ER+], 374 ER-) and 2029 controls. Gene-level analyses were conducted using improved AdaJoint test for large-scale genetic association studies adjusting for age, study site and the first four eigenvectors from the principal component analysis. SNP-level analyses were conducted with logistic regression. The Hippo pathway was significantly associated with risk of ER+ breast cancer (pathway-level P = 0.019), with WWC1 (Padj = 0.04) being the leading gene. The pathway-level significance was lost without WWC1 (P = 0.12). rs147106204 in the WWC1 gene was the most statistically significant SNP after gene-level adjustment for multiple comparisons (OR = 0.53, 95%CI = 0.41-0.70, Padj = 0.025). We found evidence of an association between genetic variations in the Hippo pathway and ER+ breast cancer. Moreover, WWC1 was identified as the most important genetic susceptibility locus highlighting the importance of genetic epidemiology studies of breast cancer in understudied populations.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/genética , Barbados , Neoplasias da Mama/etnologia , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Pessoa de Meia-Idade , Nigéria , Receptores Estrogênicos/metabolismo , Estados Unidos
11.
Clin Lung Cancer ; 19(4): 346-351, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29506890

RESUMO

BACKGROUND: Evidence favoring a multidisciplinary team (MDT) approach in the treatment of lung cancer is scarce, especially in the United States. The purpose of the present investigation was to evaluate survival outcomes of lung cancer patients treated with an MDT compared with a traditional care model. PATIENTS AND METHODS: The Stony Brook Cancer Center Registry was used to identify all lung cancer cases diagnosed between 2002 and 2016. We compared survival outcomes among 1956 lung cancer patients participating in our institution's Lung Cancer Evaluation Center's (LCEC) MDT program and 2315 lung cancer patients receiving traditional care. Log-ranks tests were used to evaluate differences in the 1-, 3-, 5-, and 10-year survival outcomes between the 2 groups. To address inherent biases, Cox proportional hazard models were used to estimate the effects on survival outcomes and adjust for possible confounders. Propensity matching was also performed to account for the effects of selection bias. RESULTS: The 5-year survival rates in the propensity-matched sample were one third greater among LCEC patients compared with those receiving a traditional care approach (33.6% vs. 23.0%; P < .001). After adjusting for potential confounders in the multivariable propensity-matched analyses, the LCEC model demonstrated a significant beneficial effect on 5-year survival outcomes compared with the standard treatment model (hazard ratio, 0.65; 95% confidence interval, 0.54-0.77). CONCLUSION: The results of the present investigation suggest an improved survival benefit from usage of an MDT model versus a traditional care model in the treatment of lung cancer. Despite the use of sophisticated statistical methods to mitigate bias in a nonrandomized study, additional research is needed to determine the extent to which an MDT approach for lung cancer influences patient outcomes.


Assuntos
Prestação Integrada de Cuidados de Saúde/métodos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Oncologia/métodos , Equipe de Assistência ao Paciente/organização & administração , Idoso , Prestação Integrada de Cuidados de Saúde/organização & administração , Feminino , Humanos , Masculino , Oncologia/organização & administração , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos
12.
Breast Cancer Res Treat ; 168(3): 703-712, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29302764

RESUMO

BACKGROUND: Few studies have evaluated the performance of existing breast cancer risk prediction models among women of African ancestry. In replication studies of genetic variants, a change in direction of the risk association is a common phenomenon. Termed flip-flop, it means that a variant is risk factor in one population but protective in another, affecting the performance of risk prediction models. METHODS: We used data from the genome-wide association study (GWAS) of breast cancer in the African diaspora (The Root consortium), which included 3686 participants of African ancestry from Nigeria, USA, and Barbados. Polygenic risk scores (PRSs) were constructed from the published odds ratios (ORs) of four sets of susceptibility loci for breast cancer. Discrimination capacity was measured using the area under the receiver operating characteristic curve (AUC). RESULTS: Flip-flop phenomenon was observed among 30~40% of variants across studies. Using the 34 variants with consistent directionality among previous studies, we constructed a PRS with AUC of 0.531 (95% confidence interval [CI]: 0.512-0.550), which is similar to the PRS using 93 variants and ORs from European ancestry populations (AUC = 0.525, 95% CI: 0.506-0.544). Additionally, we found the 34-variant PRS has good discriminative accuracy in women with family history of breast cancer (AUC = 0.586, 95% CI: 0.532-0.640). CONCLUSIONS: We found that PRS based on variants identified from prior GWASs conducted in women of European and Asian ancestries did not provide a comparable degree of risk stratification for women of African ancestry. Further large-scale fine-mapping studies in African ancestry populations are desirable to discover population-specific genetic risk variants.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Predisposição Genética para Doença , Prognóstico , Adulto , Grupo com Ancestrais do Continente Africano/genética , Idoso , Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/patologia , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Nigéria/epidemiologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco
13.
Int J Cancer ; 142(1): 36-43, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28891071

RESUMO

The vitamin D related pathway has been evaluated in carcinogenesis but its genetic contribution remains poorly understood. We examined single-nucleotide polymorphisms (SNPs) in the vitamin D related pathway genes using data from a genome-wide association study (GWAS) of breast cancer in the African Diaspora that included 3,686 participants (1,657 cases). Pathway- and gene-level analyses were conducted using the adaptive rank truncated product test. Odds ratios (OR) and 95% confidence intervals (CI) were estimated at SNP-level. After stringent Bonferroni corrections, we observed no significant association between variants in the vitamin D pathway and breast cancer risk at the pathway-, gene-, or SNP-level. In addition, no association was found for either the reported signals from GWASs of vitamin D related traits, or the SNPs within vitamin D receptor (VDR) binding regions. Furthermore, a decrease in genetically predicted 25(OH)D levels by Mendelian randomization was not associated with breast cancer (p = 0.23). However, an association for breast cancer with the pigment synthesis/metabolism pathway almost approached significance (pathway-level p = 0.08), driven primarily by a nonsense SNP rs41302073 in TYRP1, with an OR of 1.54 (95% CI = 1.24-1.91, padj = 0.007). In conclusion, we found no evidence to support an association between vitamin D status and breast cancer risk in women of African ancestry, suggesting that vitamin D is unlikely to have significant effect on breast carcinogenesis. Interestingly, TYRP1 might be related to breast cancer through a non-vitamin D relevant mechanism but further studies are needed.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Vitamina D/genética , Adulto , Grupo com Ancestrais do Continente Africano , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
14.
Cancer Epidemiol Biomarkers Prev ; 27(1): 116-118, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29254938

RESUMO

Background: Pancreatic cancer mutation signatures closely resemble breast cancer, suggesting that both cancers may have common predisposition mechanisms that may include commonly inherited SNPs.Methods: We examined 23 genetic variants known to be associated with pancreatic cancer as breast cancer risk factors in the Root genome-wide association study (GWAS; 1,657 cases and 2,029 controls of African diaspora) and GAME-ON/DRIVE GWAS (16,003 cases and 41,335 controls of European ancestry).Results: None of the pancreatic cancer susceptibility variants were individually associated with breast cancer risk after adjustment for multiple testing (at α = 0.002) in the two populations. In Root GWAS, a change by one SD in the polygenic risk score (PRS) was not significantly associated with breast cancer. In addition, we did not observe a trend in the relationship between PRS percentiles and breast cancer risk.Conclusions: The association between reported pancreatic cancer genetic susceptibility variants and breast cancer development in women of African or European ancestry is likely weak, if it does exist.Impact: Known GWAS-derived susceptibility variants of pancreatic cancer do not explain its shared genetic etiology with breast cancer. Cancer Epidemiol Biomarkers Prev; 27(1); 116-8. ©2017 AACR.


Assuntos
Neoplasias da Mama/genética , Neoplasias Pancreáticas/genética , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Biomarcadores Tumorais/genética , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Pancreáticas/etnologia , Fatores de Risco
15.
J Natl Cancer Inst ; 109(8)2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29117387

RESUMO

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10-12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10-10). At 13q34, the signal is located 5' of the gene IRS2 and 3' of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Loci Gênicos , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Quinase do Ponto de Checagem 2/genética , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 22 , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Masculino
16.
Carcinogenesis ; 38(8): 789-796, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28582508

RESUMO

Functional studies have elucidated the role of the mammalian target of rapamycin (mTOR) pathway in breast carcinogenesis, but to date, there is a paucity of data on its contribution to breast cancer risk in women of African ancestry. We examined 47628 SNPs in 61 mTOR pathway genes in the genome wide association study of breast cancer in the African Diaspora study (The Root consortium), which included 3686 participants (1657 cases). Pathway- and gene-level analyses were conducted using the adaptive rank truncated product (ARTP) test for 10994 SNPs that were not highly correlated (r2 < 0.8). Odds ratio (OR) and 95% confidence interval (CI) were estimated with logistic regression for each single-nucleotide polymorphism. The mTOR pathway was significantly associated with overall and estrogen receptor-negative (ER-) breast cancer risk (P = 0.003 and 0.03, respectively). PRKAG3 (Padj = 0.0018) and RPS6KA3 (Padj = 0.061) were the leading genes for the associations with overall breast cancer risk and ER- breast cancer risk, respectively. rs190843378 in PRKAG3 was statistically significant after gene-level adjustment for multiple comparisons (OR = 0.50 for each T allele, 95% CI = 0.38-0.66, Padj = 3.6E-05), with a statistical power of 0.914. These results provide new insights on the biological relevance of the mTOR pathway in breast cancer progression and underscore the need for more genetic epidemiology studies of breast cancer in the African Diaspora.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Neoplasias da Mama/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Serina-Treonina Quinases TOR/genética , Grupo com Ancestrais do Continente Africano/genética , Alelos , Neoplasias da Mama/patologia , Carcinogênese/genética , Carcinogênese/patologia , Receptor alfa de Estrogênio/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Transdução de Sinais
17.
Soc Sci Med ; 187: 1-10, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28645039

RESUMO

BACKGROUND: Improvements in colorectal cancer (CRC) mortality reflect the distribution of effective preventions. Social inequalities often generate unequal diffusion of medical interventions, resulting in disparate outcomes while preventions are being disseminated throughout the population. This study used a novel method to examine whether Race (Black versus White) and SES influenced when rates of CRC mortality started to decline, and how rapidly they did so. METHOD: Mortality counts from 1968-2010 were derived from death certificates of U.S. residents aged 25 + years. Individuals' race, age, county of residence, and sex were collected from death certificates. County-level SES was measured using the decennial U.S. census. Layered joinpoint regression was used to model CRC mortality trends over time. Acceleration in rates of historical decline were used to indicate preventability within counties. RESULTS: Black race was associated with a 4.1-year delay in colonoscopy-attributable declines in CRC mortality and each standard deviation unit change in SES with a 5.7-year delay in such mortality. Following the onset of a decline, colonoscopy-attributable mortality change was slower by 0.5% among Blacks, and 2.0%/standard deviation in SES. Modifying the rapidity of colonoscopy uptake could have averted 12-14,000 and 83-86,000 deaths among Blacks and residents of lower SES counties, respectively. CONCLUSIONS: Successful interventions do not uniformly benefit the U.S. POPULATION: This study highlighted the notable impact that substantial delays in the provision of interventions, and in the relative rapidity of dissemination, and estimated the extent to which there was a preventable loss of life concentrated amongst the most disadvantaged. A more egalitarian delivery of life-saving interventions could drastically reduce mortality by improving effectiveness of interventions while also addressing inequalities in health.


Assuntos
Neoplasias Colorretais/mortalidade , Grupos de Populações Continentais/estatística & dados numéricos , Renda/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Colonoscopia/mortalidade , Colonoscopia/tendências , Neoplasias Colorretais/epidemiologia , Atestado de Óbito , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Análise Multivariada , Estados Unidos/epidemiologia
18.
NPJ Breast Cancer ; 3: 5, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28649645

RESUMO

A coding region polymorphism exists in the TP53 gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia. We used multivariable logistic regression to estimate associations between the TP53 Pro47Ser allele and overall breast cancer risk. Because polymorphisms in TP53 tend to be associated with cancer risk in pre-menopausal women, we also limited our analyses to this population in the AMBER and ROOT consortia, where menopausal status was known, and conducted a fixed effects meta-analysis. In an analysis of all women in the AMBER, ROOT, and AABC consortia, we found no evidence for association of the Pro47Ser variant with breast cancer risk. However, when we restricted our analysis to only pre-menopausal women from the AMBER and ROOT consortia, there was a per allele odds ratio of 1.72 (95% confidence interval 1.08-2.76; p-value = 0.023). Although the Pro47Ser variant was not associated with overall breast cancer risk, it may increase risk among pre-menopausal women of African ancestry. Following up on more studies in human populations may better elucidate the role of this variant in breast cancer etiology. However, because of the low frequency of the polymorphism in women of African ancestry, its impact at a population level may be minimal.

19.
Cancer Epidemiol Biomarkers Prev ; 26(7): 1016-1026, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28377418

RESUMO

Background: Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry.Methods: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT).Results: Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant (P < 0.05). Through fine-mapping, in six regions (3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions (11q13, 16q12/TOX3), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality.Conclusions: Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry.Impact: The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. Cancer Epidemiol Biomarkers Prev; 26(7); 1016-26. ©2017 AACR.


Assuntos
Afro-Americanos/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença , Alelos , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Mapeamento Cromossômico , Feminino , Loci Gênicos , Humanos , Polimorfismo de Nucleotídeo Único , Receptores Estrogênicos/metabolismo , Fatores de Risco
20.
J Med Screen ; 24(4): 208-213, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28201949

RESUMO

Objective Current lung cancer screening criteria based primarily on outcomes from the National Lung Screening Trial may not adequately capture all subgroups of the population at risk. We aimed to evaluate the efficacy of lung cancer screening criteria recommended by the United States Preventive Services Task Force, Centers for Medicare and Medicaid Services, and the National Comprehensive Cancer Network in identifying known cases of lung cancer. Methods An investigation of the Stony Brook Cancer Center Lung Cancer Evaluation Center's database identified 1207 eligible, biopsy-proven lung cancer cases diagnosed between January 1996 and March 2016. Age at diagnosis, smoking history, and other known risk factors for lung cancer were used to determine the proportion of cases that would have met current United States Preventive Services Task Force, Centers for Medicare and Medicaid Services, and National Comprehensive Cancer Network eligibility requirements for lung cancer screening. Results Of the 1046 ever smokers in the study, 40% did not meet the National Lung Screening Trial age requirements, 20% did not have a ≥30 pack year smoking history, and approximately one-third quit smoking >15 years before diagnosis, thus deeming them ineligible for screening. Applying the United States Preventive Services Task Force, Centers for Medicare and Medicaid Services, and National Comprehensive Cancer Network eligibility criteria to the Stony Brook Cancer Center's Lung Cancer Evaluation Center cases, 49.2, 46.3, and 69.8%, respectively, would have met the current lung cancer screening guidelines. Conclusions The United States Preventive Services Task Force and Centers for Medicare and Medicaid Services eligibility criteria for lung cancer screening captured less than 50% of lung cancer cases in this investigation. These findings highlight the need to reevaluate the efficacy of current guidelines and may have major public health implications.


Assuntos
Detecção Precoce de Câncer/normas , Neoplasias Pulmonares/diagnóstico , Guias de Prática Clínica como Assunto , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/organização & administração , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Fatores de Risco , Fumar/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Estados Unidos
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