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1.
Nat Commun ; 12(1): 1236, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33623038

RESUMO

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10-180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

2.
Clin Cancer Res ; 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33500355

RESUMO

PURPOSE: In metastatic castrate-sensitive prostate cancer (mCSPC), combined androgen axis inhibition is a standard of care. Noninvasive biomarkers that guide initial therapy decisions are needed. We hypothesized that CellSearch circulating tumor cell (CTC) count, an FDA-cleared assay in metastatic castrate-resistant prostate cancer (mCRPC), is a relevant biomarker in mCSPC. EXPERIMENTAL DESIGN: SWOG S1216 is a phase III prospective randomized trial of androgen deprivation therapy (ADT) combined with orteronel or bicalutamide for mCSPC. CellSearch CTC count was measured at registration (baseline). Prespecified CTC cut-off points of 0, 1-4, and ≥5 were correlated with baseline patient characteristics and, in a stratified subsample, were also correlated with two prespecified trial secondary endpoints: 7-month PSA ≤0.2 ng/mL versus 0.2-4.0 versus >4.0 (intermediate endpoint for overall survival); and progression-free survival (PFS) ≤ versus >2 years. RESULTS: A total of 523 patients submitted baseline samples, and CTCs were detected (median 3) in 33%. Adjusting for two trial stratification factors (disease burden and timing of ADT initiation), men with undetectable CTCs had nearly nine times the odds of attaining 7-month PSA ≤ 0.2 versus > 4.0 [OR 8.8, 95% confidence interval (CI), 2.7-28.6, P < 0.001, N = 264] and four times the odds of achieving > 2 years PFS (OR 4.0, 95% CI, 1.9-8.5, P < 0.001, N = 336) compared with men with baseline CTCs ≥5. CONCLUSIONS: Baseline CTC count in mCSPC is highly prognostic of 7-month PSA and 2-year PFS after adjusting for disease burden and discriminates men who are likely to experience poor survival outcomes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33420416

RESUMO

BACKGROUND: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). MATERIALS AND METHOD: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy. RESULTS: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer. CONCLUSIONS: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

4.
Cancers (Basel) ; 12(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158149

RESUMO

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

5.
JCO Precis Oncol ; 4: 32-43, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32832836

RESUMO

PURPOSE: In studies of men of European ancestry, rare pathogenic variants in DNA repair pathway genes have been shown to be associated with risk of aggressive prostate cancer. The contribution of rare coding variation to prostate cancer risk in men of African ancestry has not been established. METHODS: We sequenced a panel of 19 DNA repair and cancer predisposition genes in 2,453 African American and 1,151 Ugandan prostate cancer cases and controls. Rare variants were classified as pathogenic or putatively functionally disruptive and examined in association with prostate cancer risk and disease aggressiveness in gene and pathway-level association analyses. RESULTS: Pathogenic variants were found in 75 out of 2,098 cases (3.6%) and 31 out of 1,481 controls (2.1%) (OR=1.82, 95% CI=1.19 to 2.79, P=0.0044) with the association being stronger for more aggressive disease phenotypes (OR=3.10, 95% CI=1.54 to 6.23, P=0.0022). The highest risks for aggressive disease were observed with pathogenic variants in the ATM, BRCA2, PALB2 and NBN genes, with odds ratios ranging from ~4 to 15 in the combined study sample of African American and Ugandan men. Rare, non-pathogenic, non-synonymous variants did not have a major impact on risk of overall prostate cancer or disease aggressiveness. CONCLUSIONS: Rare pathogenic variants in DNA repair genes have appreciable effects on risk of aggressive prostate cancer in men of African ancestry. These findings have potential implications for panel testing and risk stratification in this high-risk population.

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.
J Assist Reprod Genet ; 37(6): 1459-1466, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32372302

RESUMO

PURPOSE: Tyrosine kinase inhibitors (TKIs) such as imatinib are commonly used chemotherapeutics, but the effects of long-term treatments on reproductive outlook for cancer survivors are unknown. The purpose of this study was to examine the effects of long-term imatinib treatments on follicle development and embryo quality. Since prospective studies are not possible in healthy humans, we have incorporated a commonly used mouse model. METHODS: Adult female mice were treated with daily IP injections of imatinib for 4-6 weeks. Liquid chromatography-mass spectrometry was used to measure imatinib in serum and ovarian tissues. At the end of treatments, females were superovulated and mated to yield fertilized embryos. Oocytes and embryos were collected from oviducts, assessed for development by microscopy, and fertilized embryos were cultured in vitro. Blastocysts were fixed and stained for differential cell counts. RESULTS: Long-term imatinib treatments caused a shift in follicle development, with imatinib-treated females having fewer primordial follicles, but an increase in primary and secondary follicles (P < 0.05). There was no effect on ovulation or fertilization rates. However, blastocysts from imatinib-treated females had fewer total cells (P < 0.05) and a significant shift from inner cell mass to increased trophectoderm cells. CONCLUSION: This pilot study indicates that long-term TKI treatments may have significant impact on ovarian reserve and embryo developmental capacity. More studies are needed in other model systems to determine the long-term impact of TKIs in patients. Knowing the potential effects of chemotherapeutics on reproductive outlook is critical for quality of life and more research is needed.

8.
Int J Cancer ; 147(7): 1808-1822, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32064598

RESUMO

We pooled multiethnic data from four population-based studies and examined associations of menstrual and reproductive characteristics with breast cancer (BC) risk by tumor hormone receptor (HR) status [defined by estrogen receptor (ER) and progesterone receptor (PR)]. We estimated odds ratios and 95% confidence intervals using multivariable logistic regression, stratified by age (<50, ≥50 years) and ethnicity, for 5,186 HR+ (ER+ or PR+) cases, 1,365 HR- (ER- and PR-) cases and 7,480 controls. For HR+ BC, later menarche and earlier menopause were associated with lower risk in non-Hispanic whites (NHWs) and Hispanics, and higher parity and longer breast-feeding were associated with lower risk in Hispanics and Asian Americans, and suggestively in NHWs. Positive associations with later first full-term pregnancy (FTP), longer interval between menarche and first FTP and shorter time since last FTP were limited to younger Hispanics and Asian Americans. Except for nulliparity, reproductive characteristics were not associated with risk in African Americans. For HR- BC, lower risk was associated with later menarche, except in African Americans and older Asian Americans and with longer breast-feeding in Hispanics and Asian Americans only. In younger African Americans, HR- BC risk associated with higher parity (≥3 vs. 1 FTP) was increased fourfold in women who never breast-fed, but not in those with a breast-feeding history, suggesting that breast-feeding may mitigate the adverse effect of higher parity in younger African American women. Further work needs to evaluate why menstrual and reproductive risk factors vary in importance according to age and ethnicity.

9.
Int J Cancer ; 146(7): 1819-1826, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31226226

RESUMO

Latinos represent <1% of samples analyzed to date in genome-wide association studies of cancer. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts across populations. In the present study, we performed a GWAS of prostate cancer (PrCa) in 2,820 Latino PrCa cases and 5,293 controls to search for novel PrCa risk loci and to examine the generalizability of known PrCa risk loci in Latino men. We also conducted a genetic admixture-mapping scan to identify PrCa risk alleles associated with local ancestry. Genome-wide significant associations were observed with 84 variants all located at the known PrCa risk regions at 8q24 (128.484-128.548) and 10q11.22 (MSMB gene). In admixture mapping, we observed genome-wide significant associations with local African ancestry at 8q24. Of the 162 established PrCa risk variants that are common in Latino men, 135 (83.3%) had effects that were directionally consistent as previously reported, among which 55 (34.0%) were statistically significant with p < 0.05. A polygenic risk model of the known PrCa risk variants showed that, compared to men with average risk (25th-75th percentile of the polygenic risk score distribution), men in the top 10% had a 3.19-fold (95% CI: 2.65, 3.84) increased PrCa risk. In conclusion, we found that the known PrCa risk variants can effectively stratify PrCa risk in Latino men. Larger studies in Latino populations will be required to discover and characterize genetic risk variants for PrCa and improve risk stratification for this population.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hispano-Americanos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Idoso , Alelos , Biomarcadores Tumorais , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Razão de Chances , Polimorfismo de Nucleotídeo Único
10.
Epidemiology ; 30(3): 449-457, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30964816

RESUMO

BACKGROUND: Data on breastfeeding and breast cancer risk are sparse and inconsistent for Hispanic women. METHODS: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the United States and Mexico, we examined the association of breastfeeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, and the joint effects of breastfeeding, parity, and age at first birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RESULTS: Among parous Hispanic women, older age at first birth was associated with increased breast cancer risk, whereas parity was associated with reduced risk. These associations were found for hormone receptor positive (HR+) breast cancer only and limited to premenopausal women. Age at first birth and parity were not associated with risk of ER- and PR- breast cancer. Increasing duration of breastfeeding was associated with decreasing breast cancer risk (≥25 vs. 0 months: OR = 0.73; 95% CI = 0.60, 0.89; Ptrend = 0.03), with no heterogeneity by menopausal status or subtype. At each parity level, breastfeeding further reduced HR+ breast cancer risk. Additionally, breastfeeding attenuated the increase in risk of HR+ breast cancer associated with older age at first birth. CONCLUSIONS: Our findings suggest that breastfeeding is associated with reduced risk of both HR+ and ER- and PR- breast cancer among Hispanic women, as reported for other populations, and may attenuate the increased risk in women with a first pregnancy at older ages.


Assuntos
Aleitamento Materno/etnologia , Neoplasias da Mama/etnologia , Hispano-Americanos/estatística & dados numéricos , Paridade , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Adulto , Idoso , Aleitamento Materno/estatística & dados numéricos , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Estados Unidos/epidemiologia
12.
Nat Commun ; 9(1): 4616, 2018 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-30397198

RESUMO

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10-15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.


Assuntos
Cromossomos Humanos Par 8/genética , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Mapeamento Cromossômico , Suscetibilidade a Doenças , Marcadores Genéticos , Predisposição Genética para Doença/epidemiologia , Genótipo , Haplótipos , Humanos , Masculino , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Medição de Risco , Fatores de Risco
13.
Cancer Causes Control ; 29(10): 951-966, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30136012

RESUMO

PURPOSE: The reasons behind socio-economic disparities in prostate cancer incidence remain unclear. We tested the hypothesis that individual-level factors act jointly with neighborhood-level social and built environment factors to influence prostate cancer risk and that specific social and built environment factors contribute to socio-econmic differences in risk. METHODS: We used multi-level data, combining individual-level data (including education and known prostate cancer risk factors) for prostate cancer cases (n = 775) and controls (n = 542) from the San Francisco Bay Area Prostate Cancer Study, a population-based case-control study, with contextual-level data on neighborhood socio-economic status (nSES) and specific social and built environment factors from the California Neighborhoods Data System. Multivariable logistic regression models were used to compute adjusted odds ratios separately for localized and advanced stage prostate cancer while controlling for neighborhood clustering. RESULTS: We found a more than twofold increased risk of both localized and advanced prostate cancer with increasing levels of nSES, and decreased risk of advanced prostate cancer with increasing levels of education. For localized disease, the nSES association was largely explained by known prostate cancer risk factors and specific neighborhood environment factors; population density, crowding, and residential mobility. For advanced disease, associations with education and nSES were not fully explained by any available individual- or neighborhood-level factors. CONCLUSIONS: These results demonstrate the importance of specific neighborhood social and built environment factors in understanding risk of localized prostate cancer. Further research is needed to understand the factors underpinning the associations between individual- and neighborhood-level SES and risk of advanced prostate cancer.


Assuntos
Neoplasias da Próstata/epidemiologia , Características de Residência , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , São Francisco/epidemiologia , Classe Social , Fatores Socioeconômicos
14.
PLoS One ; 13(4): e0195666, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29641614

RESUMO

BACKGROUND: Circulating melatonin is a good candidate biomarker for studies of circadian rhythms and circadian disruption. However, epidemiologic studies on circulating melatonin are limited because melatonin is secreted at night, yet most epidemiologic studies collect blood during the day when melatonin levels are very low, and assays are lacking that are ultrasensitive to detect low levels of melatonin reliably. OBJECTIVE: To assess the performance of a refined radioimmunoassay in measuring morning melatonin among women. METHODS: We used morning serum samples from 47 postmenopausal women ages 48-80 years without a history of breast cancer who participated in the San Francisco Bay Area Breast Cancer Study, including 19 women who had duplicate measurements. The coefficient of variation (CV) and intraclass coefficient (ICC) were estimated using the random effect model. RESULTS: Reproducibility for the assay was satisfactory, with a CV of 11.2% and an ICC of 98.9%; correlation between the replicate samples was also high (R = 0.96). In the 47 women, serum melatonin levels ranged from 0.6 to 62.6 pg/ml, with a median of 7.0 pg/ml. CONCLUSION: Our results suggest that it is possible to reliably measure melatonin in postmenopausal women in morning serum samples in large epidemiologic studies to evaluate the role of melatonin in cancer etiology or prognosis.


Assuntos
Análise Química do Sangue/métodos , Neoplasias da Mama/sangue , Estudos Epidemiológicos , Melatonina/sangue , Pós-Menopausa/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Tempo
15.
Pregnancy Hypertens ; 12: 144-149, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29580923

RESUMO

OBJECTIVE: The purpose of this study was to validate our previous genetic association findings related to the endoglin (ENG) pathway from an American Caucasian preeclampsia cohort in independent preeclampsia cohorts. We also sought to explore the ENG pathway for new genetic associations in these independent cohorts. STUDY DESIGN: We used a tagging single nucleotide (tSNP) approach to assess genetic variability across five ENG pathway genes (ENG, TGFß1, TGFßR1, ALK1, and TGFßR2) in a Caucasian cohort from Norway (n = 77 preeclampsia cases & n = 63 normotensive controls) and a White Hispanic cohort from Southern California (n = 69 preeclampsia cases & n = 106 normotensive controls). MAIN OUTCOME MEASURES: Univariate analyses (Chi Square, Fisher's Exact) and multivariate logistic regression were conducted to evaluate the association between tSNP genotype distributions and pregnancy outcome in each cohort. Logistic regression models were adjusted for maternal age at delivery, infant sex, parity, smoking during pregnancy, and pre-pregnancy BMI. RESULTS: Although we were unable to replicate our previous SNP-specific findings (ENG rs11792480, rs10121110; TGFßR2 rs6550005; p's > 0.05), we found that genetic variation in TGFßR1[ALK5] (rs6478974) and TGFßR2 (rs11129420, rs6802220, rs1155708, rs3773640, rs3773663) was significantly associated with preeclampsia in the Norwegian cohort and genetic variation in ALK1 (rs706819) and TGFßR2 (rs9843942) was significantly associated with preeclampsia in the Latina cohort. CONCLUSION: Overall, our results provide further support for the involvement and investigation of the endoglin pathway in preeclampsia.


Assuntos
Endoglina/genética , Grupo com Ancestrais do Continente Europeu/genética , Hispano-Americanos/genética , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genética , Receptores de Activinas Tipo II/genética , Adolescente , Adulto , California/epidemiologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Análise Multivariada , Noruega/epidemiologia , Fenótipo , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/etnologia , Gravidez , Proteínas Serina-Treonina Quinases/genética , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/genética , Fatores de Risco , Fator de Crescimento Transformador beta1/genética , Adulto Jovem
17.
Nutr J ; 17(1): 3, 2018 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-29306332

RESUMO

BACKGROUND: Despite the numerous associations of vitamin D with health and disease, vitamin D deficiency is still common from a global perspective. While basic research, clinical and preventive activities grow constantly in vitamin D research, there is no in-depth analysis of the related global scientific productivity available so far. METHODS: Density equalizing mapping procedures (DEMP) were combined with socioeconomic benchmarks using the NewQIS platform. RESULTS: A total of 25,992 vitamin D-related research articles were identified between 1900 to 2014 with a significant increase (r2 = .6541) from 1900 to 2014. Authors located in Northern America - especially in the USA - distributed the majority of global vitamin D research, followed by their Western European counterparts. DEMP-analysis illustrates that Africa and South America exhibit only minor scientific productivity. Among high-income group countries, Scandinavian nations such as Denmark or Finland (2147.9 and 1607.7 vitamin D articles per GDP in 1000 billion USD) were highly active with regard to socioeconomic figures. CONCLUSION: Networks dedicated to vitamin D research are present around the world. Overall, the Northern American and Western European nations occupy prominent positions. However, South American, African and Asian countries apart from Japan only play a minor role in the global research production related to vitamin D. Since vitamin D deficiency is currently increasing in the Americas, Europe and parts of the Middle East, research in these regions may need to be encouraged.


Assuntos
Internacionalidade , Projetos de Pesquisa , Deficiência de Vitamina D/epidemiologia , África/epidemiologia , Ásia/epidemiologia , Australásia/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Oriente Médio/epidemiologia , América do Norte/epidemiologia , Fatores Socioeconômicos , América do Sul/epidemiologia
18.
Cancer Epidemiol ; 53: 1-11, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29328959

RESUMO

BACKGROUND: We addressed the hypothesis that individual-level factors act jointly with social and built environment factors to influence overall survival for men with prostate cancer and contribute to racial/ethnic and socioeconomic (SES) survival disparities. METHODS: We analyzed multi-level data, combining (1) individual-level data from the California Collaborative Prostate Cancer Study, a population-based study of non-Hispanic White (NHW), Hispanic, and African American prostate cancer cases (N = 1800) diagnosed from 1997 to 2003, with (2) data on neighborhood SES (nSES) and social and built environment factors from the California Neighborhoods Data System, and (3) data on tumor characteristics, treatment and follow-up through 2009 from the California Cancer Registry. Multivariable, stage-stratified Cox proportional hazards regression models with cluster adjustments were used to assess education and nSES main and joint effects on overall survival, before and after adjustment for social and built environment factors. RESULTS: African American men had worse survival than NHW men, which was attenuated by nSES. Increased risk of death was associated with residence in lower SES neighborhoods (quintile 1 (lowest nSES) vs. 5: HR = 1.56, 95% CI: 1.11-2.19) and lower education (

Assuntos
Neoplasias da Próstata/epidemiologia , Características de Residência , Fatores Socioeconômicos , Afro-Americanos , Idoso , California , Grupos de Populações Continentais , Grupos Étnicos , Grupo com Ancestrais do Continente Europeu , Hispano-Americanos , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Classe Social
19.
Int J Cancer ; 142(11): 2273-2285, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29330856

RESUMO

Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population-based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast-feeding. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression. For younger women, aged <50 years, TNBC risk was increased two-fold for parous women who never breast-fed compared to nulliparous women (OR = 2.02, 95% CI = 1.12-3.63). For younger parous women, longer duration of lifetime breast-feeding was associated with a borderline reduced risk (≥24 vs. 0 months: OR = 0.52, 95% CI = 0.26-1.04, Ptrend = 0.06). Considering the joint effect of parity and breast-feeding, risk was increased two-fold for women with ≥3 full-term pregnancies (FTPs) and no or short-term (<12 months) breast-feeding compared to women with 1-2 FTPs and breast-feeding ≥12 months (OR = 2.56, 95% CI = 1.22-5.35). None of these associations were observed among older women (≥50 years). Differences in reproductive patterns possibly contribute to the ethnic differences in TNBC incidence. Among controls aged <50 years, the prevalence of no or short-term breast-feeding and ≥3 FTPs was highest for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%) and non-Hispanic whites (6%). Breast-feeding is a modifiable behavioral factor that may lower TNBC risk and mitigate the effect of FTPs in women under age 50 years.


Assuntos
Aleitamento Materno/efeitos adversos , História Reprodutiva , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/etiologia , Adulto , Fatores Etários , Idoso , California/epidemiologia , California/etnologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Vigilância da População , Sistema de Registros , Medição de Risco , Fatores de Risco , Adulto Jovem
20.
J Matern Fetal Neonatal Med ; 31(8): 1085-1091, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28320252

RESUMO

OBJECTIVE: To examine the effect of laser surgery on angiogenic and anti-angiogenic factors in patients with twin-twin transfusion syndrome (TTTS). METHODS: Cases of TTTS and uncomplicated monochorionic diamniotic twin pregnancies between 16 and 26 weeks' gestation were prospectively enrolled into the study. Maternal blood samples were obtained to measure angiogenic factors (vascular endothelial growth factor-A [VEGF], placental-derived growth factor [PlGF], and endothelin) and anti-angiogenic factors (soluble fms-like tyrosine kinase (sFlt-1), soluble endoglin (sEng), and sFlt-1/PlGF ratio). For cases, these factors were measured at visit 1 (pre-operatively), visit 2 (postoperative day one), and visit 3 (at least 3 weeks after surgery). In controls, the factors were measured at visit 1 (enrollment) and visit 2 (at least 3 weeks later). Levels of angiogenic and anti-angiogenic factors between cases and controls were compared. RESULTS: At enrollment, the TTTS cases demonstrated an anti-angiogenic state with significantly higher sFlt-1, sEng, sFlt-1/PlGF ratio, and lower PlGF. Laser surgery, comparing visit 1-3, had a partial corrective effect on TTTS cases. sFlt-1 significantly decreased several weeks after surgery. The other factors (PlGF, endothelin, sFlt-1, sEng, and sFlt-1/PlGF ratio) were not statistically significantly different by visit 3. CONCLUSION: Laser surgery partially corrected the angiogenic profile in patients with TTTS.


Assuntos
Endoglina/sangue , Transfusão Feto-Fetal/sangue , Terapia a Laser , Fator de Crescimento Placentário/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Estudos de Casos e Controles , Feminino , Terapias Fetais , Transfusão Feto-Fetal/cirurgia , Humanos , Neovascularização Fisiológica , Gravidez , Estudos Prospectivos , Adulto Jovem
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