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1.
Hepatology ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33205438

RESUMO

Hepatitis C virus (HCV) is a major risk factor for hepatocellular carcinoma (HCC), one of the deadliest cancers with increasing incidence over the past few decades (1). Direct-acting antiviral (DAA) therapy in HCV-infected patients has been shown to lower the risk of liver-related events, including HCC (2). Despite sustained virological responses (SVR >95%), the risk of developing HCC in DAA-treated HCV patients with advanced fibrosis or cirrhosis remains high at 0.3 to 1.8% per year (3). On a molecular level, persistent epigenetic changes despite DAA cure are associated with hepatic carcinogenesis (4). Current AASLD-IDSA (5) and EASL (6) guidelines recommend lifelong surveillance for HCV-cured patients with cirrhosis; therefore, a more precise identification of clinical and molecular markers associated with HCC risk among these patients will have significant cost-effectiveness and resource utilization implications.

2.
J Natl Cancer Inst ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33252629

RESUMO

BACKGROUND: The causes of racial disparities in epithelial ovarian cancer (EOC) incidence remain unclear. Differences in the prevalence of ovarian cancer risk factors may explain disparities in EOC incidence among African American (AA) and White women. METHODS: We used data from four case-control studies and three case-control studies nested within prospective cohorts in the Ovarian Cancer in Women of African Ancestry Consortium to estimate race-specific associations of ten known or suspected EOC risk factors using logistic regression. Using the Bruzzi method, race-specific population attributable risks (PAR) were estimated for each risk factor individually and collectively, including groupings of exposures (reproductive factors and modifiable factors). All statistical tests were two-sided. RESULTS: Among 3,244 White EOC cases and 9,638 controls and 1,052 AA EOC cases and 2,410 controls, AA women had a statistically significantly higher PAR (false discovery rate (FDR) P < .001) for first-degree family history of breast cancer (PAR = 10.1%, 95% CI = 6.5% to 13.7%) compared to White women (PAR = 2.6%, 95% CI = 0.8% to 4.4%). After multiple test correction, AA women had a higher PAR than White women when evaluating all risk factors collectively (PAR = 61.6%, 95% CI = 48.6% to 71.3% vs. PAR = 43.0%, 95% CI = 32.8% to 51.4%, respectively; FDR P = .06) and for modifiable exposures, including BMI, oral contraceptives, aspirin, and body powder (PAR = 36.0%, 95% CI = 21.0% to 48.8% vs. PAR = 13.8%, 95% CI = 4.5% to 21.8%, respectively; FDR P = .04). CONCLUSIONS: Collectively, the selected risk factors accounted for slightly more of the risk among AA than White women, and interventions to reduce EOC incidence that are focused on multiple modifiable risk factors may be slightly more beneficial to AA women than White women at risk for EOC.

3.
Cancer Epidemiol Biomarkers Prev ; 29(10): 2019-2025, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32732248

RESUMO

BACKGROUND: Incidence rates of epithelial ovarian cancer (EOC) vary across racial/ethnic groups, yet little is known about the impact of hormone-related EOC risk factors in non-Whites. METHODS: Among 91,625 female Multiethnic Cohort Study participants, 155 incident EOC cases were diagnosed in Whites, 93 in African Americans, 57 in Native Hawaiians, 161 in Japanese Americans, and 141 in Latinas. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between race/ethnicity and EOC risk and between hormone-related factors and EOC risk across racial/ethnic groups. RESULTS: Compared with Whites, African Americans and Japanese Americans had a lower multivariable-adjusted EOC risk; Native Hawaiians had a suggestive higher risk. Parity and oral contraceptive (OC) use were inversely associated with EOC risk (P int race/ethnicity ≥ 0.43); associations were strongest among Japanese Americans (e.g., ≥4 vs. 0 children; HR = 0.45; CI, 0.26-0.79). Age at natural menopause and postmenopausal hormone (PMH) use were not associated with EOC risk in the overall population, but were positively associated with risk in Latinas (e.g., ≥5 years vs. never PMH use; HR = 2.13; CI, 1.30-3.49). CONCLUSIONS: We observed strong associations with EOC risk for parity and OC use in Japanese Americans and PMH use and age at natural menopause in Latinas. However, differences in EOC risk among racial/ethnic groups were not fully explained by established hormone-related risk factors. IMPACT: Our study indicates there are racial/ethnic differences in EOC risk and risk factors, and could help improve prevention strategies for non-White women.

4.
Hepatol Commun ; 4(8): 1112-1123, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32766472

RESUMO

The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population-specific genetic variants associated with liver fat. We conducted a genome-wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population-based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin-like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10-15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10-8) was also observed. Rs7724941 was associated with HOMA-IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high-density lipoprotein (beta = -0.046; P = 0.04), and sex hormone binding globulin (beta = -0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association.

5.
PLoS One ; 15(7): e0236353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730345

RESUMO

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH), a subtype of non-alcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma, is characterized by hepatic inflammation. Despite evolving therapies aimed to ameliorate inflammation in NASH, the transcriptional changes that lead to inflammation progression in NAFLD remain poorly understood. The aim of this pilot study was to define transcriptional changes in early, non-fibrotic NAFLD using two independent biopsy-proven NAFLD cohorts. METHODS: We extracted RNA from liver tissue of 40 patients with biopsy-proven NAFLD based on NAFLD Activity Score (NAS) (23 patients with NAS ≤3, 17 with NAS ≥5) and 21 healthy controls, and we compared changes in expression of 594 genes involved in innate immune function. Using plasma from an independent cohort of 67 patients with NAFLD and 15 healthy controls, we validated the gene changes observed using a multiplex protein assay. RESULTS: Compared to healthy controls, NAFLD patients with NAS ≥5 had differential expression of 211 genes, while those with NAS ≤3 had differential expression of only 14 genes. Notably, osteopontin (SPP1) (3.74-fold in NAS ≤3, 8.28-fold in NAS ≥5) and CXCL10 (2.27-fold in NAS ≤3, 8.28-fold in NAS ≥5) gene expression were significantly upregulated with histologic progression of NAFLD. Plasma osteopontin (SPP1) and CXCL10 are significantly increased in the presence of NAFLD, regardless of histologic grade. In addition, the plasma levels of these two proteins distinguish clearly between the presence or absence of NAFLD (AUC>0.90). CONCLUSIONS: Osteopontin (SPP1) and CXCL10 are upregulated early in non-fibrotic NAFLD and may serve as valuable non-invasive biomarkers.


Assuntos
Quimiocina CXCL10/sangue , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Osteopontina/sangue , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Transcrição Genética , Transcriptoma/genética
6.
Front Genet ; 10: 494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178898

RESUMO

Background: Chronic kidney disease (CKD) is common and disproportionally burdens United States ethnic minorities. Its genetic determinants may differ by disease severity and clinical stages. To uncover genetic factors associated CKD severity among high-risk ethnic groups, we performed genome-wide association studies (GWAS) in diverse populations within the Population Architecture using Genomics and Epidemiology (PAGE) study. Methods: We assembled multi-ethnic genome-wide imputed data on CKD non-overlapping cases [4,150 mild to moderate CKD, 1,105 end-stage kidney disease (ESKD)] and non-CKD controls for up to 41,041 PAGE participants (African Americans, Hispanics/Latinos, East Asian, Native Hawaiian, and American Indians). We implemented a generalized estimating equation approach for GWAS using ancestry combined data while adjusting for age, sex, principal components, study, and ethnicity. Results: The GWAS identified a novel genome-wide associated locus for mild to moderate CKD nearby NMT2 (rs10906850, p = 3.7 × 10-8) that replicated in the United Kingdom Biobank white British (p = 0.008). Several variants at the APOL1 locus were associated with ESKD including the APOL1 G1 rs73885319 (p = 1.2 × 10-9). There was no overlap among associated loci for CKD and ESKD traits, even at the previously reported APOL1 locus (p = 0.76 for CKD). Several additional loci were associated with CKD or ESKD at p-values below the genome-wide threshold. These loci were often driven by variants more common in non-European ancestry. Conclusion: Our genetic study identified a novel association at NMT2 for CKD and showed for the first time strong associations of the APOL1 variants with ESKD across multi-ethnic populations. Our findings suggest differences in genetic effects across CKD severity and provide information for study design of genetic studies of CKD in diverse populations.

7.
Int J Cancer ; 145(1): 58-69, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30561796

RESUMO

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.


Assuntos
Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Idoso , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Paridade , Gravidez , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fumar/epidemiologia
8.
J Natl Cancer Inst ; 111(2): 137-145, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29860330

RESUMO

BACKGROUND: Aspirin use is associated with reduced risk of several cancers. A pooled analysis of 12 case-control studies showed a 10% decrease in ovarian cancer risk with regular aspirin use, which was stronger for daily and low-dose users. To prospectively investigate associations of analgesic use with ovarian cancer, we analyzed data from 13 studies in the Ovarian Cancer Cohort Consortium (OC3). METHODS: The current study included 758 829 women who at study enrollment self-reported analgesic use, among whom 3514 developed ovarian cancer. Using Cox regression, we assessed associations between frequent medication use and risk of ovarian cancer. Dose and duration were also evaluated. All statistical tests were two-sided. RESULTS: Women who used aspirin almost daily (≥6 days/wk) vs infrequent/nonuse experienced a 10% reduction in ovarian cancer risk (rate ratio [RR] = 0.90, 95% confidence interval [CI] = 0.82 to 1.00, P = .05). Frequent use (≥4 days/wk) of aspirin (RR = 0.95, 95% CI = 0.88 to 1.03), nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs; RR = 1.00, 95% CI = 0.90 to 1.11), or acetaminophen (RR = 1.05, 95% CI = 0.88 to 1.24) was not associated with risk. Daily acetaminophen use (RR = 1.28, 95% CI = 1.00 to 1.65, P = .05) was associated with elevated ovarian cancer risk. Risk estimates for frequent, long-term (10+ years) use of aspirin (RR = 1.15, 95% CI = 0.98 to 1.34) or nonaspirin NSAIDs (RR = 1.19, 95% CI = 0.84 to 1.68) were modestly elevated, although not statistically significantly so. CONCLUSIONS: This large, prospective analysis suggests that women who use aspirin daily have a slightly lower risk of developing ovarian cancer (∼10% lower than infrequent/nonuse)-similar to the risk reduction observed in case-control analyses. The observed potential elevated risks for 10+ years of frequent aspirin and NSAID use require further study but could be due to confounding by medical indications for use or variation in drug dosing.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Neoplasias Ovarianas/prevenção & controle , Medição de Risco/métodos , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
9.
PLoS One ; 13(7): e0200486, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30044860

RESUMO

Current knowledge of the genetic architecture of key reproductive events across the female life course is largely based on association studies of European descent women. The relevance of known loci for age at menarche (AAM) and age at natural menopause (ANM) in diverse populations remains unclear. We investigated 32 AAM and 14 ANM previously-identified loci and sought to identify novel loci in a trans-ethnic array-wide study of 196,483 SNPs on the MetaboChip (Illumina, Inc.). A total of 45,364 women of diverse ancestries (African, Hispanic/Latina, Asian American and American Indian/Alaskan Native) in the Population Architecture using Genomics and Epidemiology (PAGE) Study were included in cross-sectional analyses of AAM and ANM. Within each study we conducted a linear regression of SNP associations with self-reported or medical record-derived AAM or ANM (in years), adjusting for birth year, population stratification, and center/region, as appropriate, and meta-analyzed results across studies using multiple meta-analytic techniques. For both AAM and ANM, we observed more directionally consistent associations with the previously reported risk alleles than expected by chance (p-valuesbinomial≤0.01). Eight densely genotyped reproductive loci generalized significantly to at least one non-European population. We identified one trans-ethnic array-wide SNP association with AAM and two significant associations with ANM, which have not been described previously. Additionally, we observed evidence of independent secondary signals at three of six AAM trans-ethnic loci. Our findings support the transferability of reproductive trait loci discovered in European women to women of other race/ethnicities and indicate the presence of additional trans-ethnic associations both at both novel and established loci. These findings suggest the benefit of including diverse populations in future studies of the genetic architecture of female growth and development.


Assuntos
Variação Biológica da População/genética , Menarca/genética , Menopausa/genética , Fatores Etários , Alelos , Variação Biológica da População/etnologia , Feminino , Loci Gênicos/genética , Genótipo , Humanos , Menarca/etnologia , Menopausa/etnologia , Fenótipo , Polimorfismo de Nucleotídeo Único
11.
Curr Epidemiol Rep ; 3: 181-190, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27547694

RESUMO

Latinos have lower rates for most common cancer sites and higher rates of some less common cancers (gallbladder, liver, gastric, and cervical) than other ethnic/racial groups. Latinos are a highly heterogeneous population with diverse national origins, unique genetic admixture patterns, and wide spectrum of socio-demographic characteristics. Across the major cancers (breast, colorectal, prostate, lung, and liver) US-born Latinos have higher incidence and worse survival than foreign-born, and those with low-socioeconomic status have the lowest incidence. Puerto Rican and Cuban Latinos have higher incidence rates than Mexican Latinos. We have identified the following themes as understudied and critical to reduce the cancer burden among US Latinos: (1) etiological studies considering key sources of heterogeneity, (2) culturally sensitive cancer prevention strategies, (3) description of the molecular tumor landscape to guide treatments and improve outcomes, and (4) development of prediction models of disease risk and outcomes accounting for heterogeneity of Latinos.

12.
J Clin Oncol ; 34(24): 2888-98, 2016 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-27325851

RESUMO

PURPOSE: An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). PATIENTS AND METHODS: Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. RESULTS: Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. CONCLUSION: The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.


Assuntos
Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/epidemiologia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/epidemiologia , Adenocarcinoma Mucinoso/patologia , Adulto , Ásia/epidemiologia , Carcinoma Endometrioide/epidemiologia , Carcinoma Endometrioide/patologia , Carcinoma Epitelial do Ovário , Cistadenocarcinoma Seroso/epidemiologia , Cistadenocarcinoma Seroso/patologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , América do Norte/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco
13.
Cancer Causes Control ; 26(2): 287-296, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25534916

RESUMO

PURPOSE: Endometrial cancer (EC) is the most common gynecologic cancer in the USA. Over the last decade, the incidence rate has been increasing, with a larger increase among blacks. The aim of this study was to compare risk factors for EC in black and white women. METHODS: Data from seven cohort and four case-control studies were pooled. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95 % confidence intervals for each risk factor in blacks and whites separately. RESULTS: Data were pooled for 2,011 black women (516 cases and 1,495 controls) and 19,297 white women (5,693 cases and 13,604 controls). BMI ≥ 30 was associated with an approximate threefold increase in risk of EC in both black and white women (ORblack 2.93, 95 % CI 2.11, 4.07 and ORwhite 2.99, 95 % CI 2.74, 3.26). Diabetes was associated with a 30-40 % increase in risk among both groups. Increasing parity was associated with decreasing risk of EC in blacks and whites (p value = 0.02 and <0.001, respectively). Current and former smoking was associated with decreased risk of EC among all women. Both black and white women who used oral contraceptives for 10 +years were also at reduced risk of EC (OR 0.49, 95 % CI 0.27, 0.88 and OR 0.69, 95 % CI 0.58, 0.83, respectively). Previous history of hypertension was not associated with EC risk in either group. CONCLUSIONS: The major known risk factors for EC exert similar effects on black and white women. Differences in the incidence rates between the two populations may be due to differences in the prevalence of risk factors.


Assuntos
Neoplasias do Endométrio/etnologia , Neoplasias do Endométrio/epidemiologia , Adolescente , Adulto , Afro-Americanos , Grupo com Ancestrais do Continente Africano , Idoso , Estudos de Casos e Controles , Criança , Estudos de Coortes , Anticoncepcionais Orais/uso terapêutico , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/etnologia , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Hipertensão/complicações , Incidência , Modelos Logísticos , Idade Materna , Menarca , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Adulto Jovem
14.
Cancer ; 120(23): 3707-16, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25081299

RESUMO

BACKGROUND: Men are 4 to 8 times more likely to develop hepatocellular carcinoma (HCC) than women. Preclinical models have suggested a role for sex hormones in the development of HCC. In the current study, the authors investigated the impact of age, sex, race, and ethnicity on the survival of patients with HCC using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients diagnosed with HCC from 1988 through 2010 were identified from the SEER registry. Hazard ratios (HR) for overall survival (OS) were derived using the Cox regression model adjusted for race, year of diagnosis, marital status, treatment, birthplace, tumor differentiation, and tumor size. RESULTS: A total of 39,345 patients were identified; 76% were men and 34% were women (50% white, 12% African American, 21% Asian, 16% Hispanic, and 1% Native American). The median age at the time of diagnosis was 61 years for men and 67 years for women. Approximately 84% of patients had liver-limited disease and 16% had metastatic disease. Treatment information was available for patients diagnosed after 1998 (34,674 patients): 11% received liver-directed therapy, 11% underwent surgical resection, and 7% underwent liver transplantation. The HR for the OS of women versus men was 0.83 (95% confidence interval [95% CI], 0.77-0.88) for patients aged <55 years. The protective effect of sex on OS was found to be greatest in patients aged 18 to 44 years (HR, 0.75; 95% CI, 0.65-0.86 [P<.001]), especially those with surgically resected tumors (HR, 0.68; 95% CI, 0.54-0.86 [P = .001]) and those who were African American (HR, 0.85; 95% CI, 0.78-0.92 [P<.001]). There was no survival difference between sexes noted among Hispanics or patients aged >65 years. CONCLUSIONS: Sex appears to be associated with survival in patients with HCC. The role of androgens and estrogens in the development and progression of HCC warrants further investigation.


Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Fatores Sexuais , Adolescente , Adulto , Afro-Americanos/estatística & dados numéricos , Fatores Etários , Idoso , Americanos Asiáticos/estatística & dados numéricos , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/terapia , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Hepatectomia , Hispano-Americanos/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Programa de SEER , Adulto Jovem
15.
Hum Mol Genet ; 19(19): 3873-84, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20634197

RESUMO

There is extensive evidence that increases in blood and tissue concentrations of steroid hormones and of insulin-like growth factor I (IGF-I) are associated with breast cancer risk. However, studies of common variation in genes involved in steroid hormone and IGF-I metabolism have yet to provide convincing evidence that such variants predict breast cancer risk. The Breast and Prostate Cancer Cohort Consortium (BPC3) is a collaboration of large US and European cohorts. We genotyped 1416 tagging single nucleotide polymorphisms (SNPs) in 37 steroid hormone metabolism genes and 24 IGF-I pathway genes in 6292 cases of breast cancer and 8135 controls, mostly Caucasian, postmenopausal women from the BPC3. We also imputed 3921 additional SNPs in the regions of interest. None of the SNPs tested was significantly associated with breast cancer risk, after correction for multiple comparisons. The results remained null when cases and controls were stratified by age at diagnosis/recruitment, advanced or nonadvanced disease, body mass index, with or without in situ cases; or restricted to Caucasians. Among 770 estrogen receptor-negative cases, an SNP located 3' of growth hormone receptor (GHR) was marginally associated with increased risk after correction for multiple testing (P(trend) = 1.5 × 10(-4)). We found no significant overall associations between breast cancer and common germline variation in 61 genes involved in steroid hormone and IGF-I metabolism in this large, comprehensive study. Although previous studies have shown that variations in these genes can influence endogenous hormone levels, the magnitude of the effect of single SNPs does not appear to be sufficient to alter breast cancer risk.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Hormônios Esteroides Gonadais/genética , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Idoso , Estudos de Coortes , Feminino , Hormônios Esteroides Gonadais/metabolismo , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Controle de Qualidade , Fatores de Risco , Estados Unidos
16.
Carcinogenesis ; 31(8): 1392-9, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20547493

RESUMO

BACKGROUND: It is well established that estrogen increases endometrial cancer risk, whereas progesterone opposes the estrogen effects. The PROGINS allele of the progesterone receptor (PGR) gene reduces the function of PGR and has been associated with increased risk of the endometrioid type ovarian cancer. We investigated whether genetic variation in PGR is also associated with endometrial cancer risk using a haplotype-based approach. METHODS: We pooled data from two endometrial cancer case-control studies that were nested within two prospective cohorts, the Multiethnic Cohort Study and the California Teachers Study. Seventeen haplotype-tagging single nucleotide polymorphisms (SNPs) across four linkage disequilibrium (LD) blocks spanning the PGR locus were genotyped in 583 incident cases and 1936 control women. Odds ratios (ORs) and 95% confidence intervals (CIs) associated with each haplotype were estimated using conditional logistic regression, stratified by age and ethnicity. RESULTS: Genetic variation in LD block 3 of the PGR locus was associated with endometrial cancer risk (P(global test) = 0.002), with haplotypes 3C, 3D and 3F associated with 31-34% increased risk. Among whites (383 cases/840 controls), genetic variation in all four blocks was associated with increased endometrial cancer risk (P(global test) = 0.010, 0.013, 0.005 and 0.020). Haplotypes containing the PROGINS allele and several haplotypes in blocks 1, 3 and 4 were associated with 34-77% increased risk among whites. SNP analyses for whites suggested that rs608995, partially linked to the PROGINS allele (r(2) = 0.6), was associated with increased risk (OR = 1.30, 95% CI = 1.06-1.59). CONCLUSIONS: Our results suggest that genetic variation in the PGR region is associated with endometrial cancer risk.


Assuntos
Neoplasias do Endométrio/genética , Variação Genética , Receptores de Progesterona/genética , Grupo com Ancestrais do Continente Africano/genética , Sequência de Bases , Neoplasias do Endométrio/epidemiologia , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Ligação Genética , Genótipo , Haplótipos/genética , Hawaii , Hispano-Americanos/genética , Humanos , Razão de Chances , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
17.
Am J Epidemiol ; 172(1): 47-57, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20562187

RESUMO

Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of > or =75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically.


Assuntos
Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/prevenção & controle , Neoplasias Renais/epidemiologia , Neoplasias Renais/prevenção & controle , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Vitamina D/uso terapêutico , Adulto , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Feminino , Finlândia/epidemiologia , Humanos , Modelos Logísticos , Masculino , Metanálise como Assunto , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/prevenção & controle
18.
Am J Epidemiol ; 172(1): 36-46, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20562189

RESUMO

A nested case-control study, including 830 cases and 992 controls from 7 cohorts, was conducted to evaluate the association of circulating 25-hydroxyvitamin D (25(OH)D), the best indicator of vitamin D status, with risk of endometrial cancer. Matching factors included age at blood donation, date of blood donation, and race. Conditional logistic regression was used in the main analysis. The median concentration of 25(OH)D was slightly lower in cases (49.4 nmol/L) than in controls (50.8 nmol/L) (P = 0.08). However, there was no association between 25(OH)D concentration and disease risk, after adjustment for body mass index. Compared with the 50-<75 nmol/L 25(OH)D category, the body mass index-adjusted odds ratios and 95% confidence intervals were 1.08 (95% confidence interval: 0.73, 1.57) for the <25 nmol/L category and 0.90 (95% confidence interval: 0.51, 1.58) for the > or =100 nmol/L category (P(trend) = 0.99). Similarly null results were observed after further adjustment for other known risk factors and in stratified analyses. Although an effect of circulating 25(OH)D at high concentrations cannot be ruled out (the highest category of 25(OH)D was > or =100 nmol/L, and for stratified analyses, > or =75 nmol/L), these results do not support a protective role of vitamin D against endometrial cancer.


Assuntos
Neoplasias do Endométrio/epidemiologia , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Vitamina D/uso terapêutico , Adulto , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Neoplasias do Endométrio/prevenção & controle , Feminino , Finlândia/epidemiologia , Humanos , Modelos Logísticos , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/prevenção & controle
19.
Cancer Causes Control ; 20(4): 491-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19132539

RESUMO

Endometrial cancer affects more than 40,000 women a year in the U.S. While the association of this disease with high body mass index and sex steroid hormones is well known, there are many questions about etiology that have not been resolved. Little is known about the genetic basis for risk associated with hormones or obesity, other common genetic factors associated with risk, or gene-environment interactions. E2C2, the Epidemiology of Endometrial Cancer Consortium, was formed in 2006 to provide a collaborative environment for addressing these questions by pooling data from existing studies. This allows for investigations of uncommon risk factors, risk for rare histologic subtypes, and associations within strata that cannot be achieved in individual studies. This report describes the establishment of the consortium, ongoing projects that demonstrate the advantages of collaborative efforts, and challenges faced. Overall, the consortium promises to provide an important means of furthering our knowledge about this cancer.


Assuntos
Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/genética , Recursos em Saúde/economia , Austrália , Estudos de Casos e Controles , China , Estudos de Coortes , Neoplasias do Endométrio/etiologia , Europa (Continente) , Feminino , Humanos , Cooperação Internacional , Internet , National Cancer Institute (U.S.) , Fatores de Risco , Estados Unidos
20.
Cancer Epidemiol Biomarkers Prev ; 16(10): 1973-81, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17932344

RESUMO

BACKGROUND: Estrogen receptor beta (ESR2) may play a role in modulating prostate carcinogenesis through the regulation of genes related to cell proliferation and apoptosis. METHODS: We conducted nested case-control studies in the Breast and Prostate Cancer Cohort Consortium (BPC3) that pooled 8,323 prostate cancer cases and 9,412 controls from seven cohorts. Whites were the predominant ethnic group. We characterized genetic variation in ESR2 by resequencing exons in 190 breast and prostate cancer cases and genotyping a dense set of single nucleotide polymorphisms (SNP) spanning the locus in a multiethnic panel of 349 cancer-free subjects. We selected four haplotype-tagging SNPs (htSNP) to capture common ESR2 variation in Whites; these htSNPs were then genotyped in all cohorts. Conditional logistic regression models were used to assess the association between sequence variants of ESR2 and the risk of prostate cancer. We also investigated the effect modification by age, body mass index, and family history, as well as the association between sequence variants of ESR2 and advanced-stage (>or=T3b, N1, or M1) and high-grade (Gleason sum >or=8) prostate cancer, respectively. RESULTS: The four tag SNPs in ESR2 were not significantly associated with prostate cancer risk, individually. The global test for the influence of any haplotype on the risk of prostate cancer was not significant (P = 0.31). However, we observed that men carrying two copies of one of the variant haplotypes (TACC) had a 1.46-fold increased risk of prostate cancer (99% confidence interval, 1.06-2.01) compared with men carrying zero copies of this variant haplotype. No SNPs or haplotypes were associated with advanced stage or high grade of prostate cancer. CONCLUSION: In our analysis focused on genetic variation common in Whites, we observed little evidence for any substantial association of inherited variation in ESR2 with risk of prostate cancer. A nominally significant (P < 0.01) association between the TACC haplotype and prostate cancer risk under the recessive model could be a chance finding and, in any event, would seem to contribute only slightly to the overall burden of prostate cancer.


Assuntos
Neoplasias da Mama/genética , Receptor beta de Estrogênio/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Neoplasias da Próstata/genética , Análise de Sequência de DNA/métodos , Idoso , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Estudos de Coortes , Éxons/genética , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Neoplasias da Próstata/patologia , Medição de Risco
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