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1.
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
2.
Prostate ; 77(16): 1573-1582, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28971497

RESUMO

BACKGROUND: Prospective cohort studies of circulating sex steroid hormones and prostate cancer risk have not provided a consistent association, despite evidence from animal and clinical studies. However, studies using male pattern baldness as a proxy of early-life or cumulative androgen exposure have reported significant associations with aggressive and fatal prostate cancer risk. Given that androgens underlie the development of patterned hair loss and chest hair, we assessed whether these two dermatological characteristics were associated with circulating and intraprostatic concentrations of sex steroid hormones among men diagnosed with localized prostate cancer. METHODS: We included 248 prostate cancer patients from the NCI Prostate Tissue Study, who answered surveys and provided a pre-treatment blood sample as well as fresh frozen adjacent normal prostate tissue. Male pattern baldness and chest hair density were assessed by trained nurses before surgery. General linear models estimated geometric means and 95% confidence intervals (95%CIs) of each hormone variable by dermatological phenotype with adjustment for potential confounding variables. Subgroup analyses were performed by Gleason score (<7 vs ≥7) and race (European American vs. African American). RESULTS: We found strong positive associations of balding status with serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG), and a weak association with elevated intraprostatic testosterone. Conversely, neither circulating nor intraprostatic sex hormones were statistically significantly associated with chest hair density. Age-adjusted correlation between binary balding status and three-level chest hair density was weak (r = 0.05). There was little evidence to suggest that Gleason score or race modified these associations. CONCLUSIONS: This study provides evidence that balding status assessed at a mean age of 60 years may serve as a clinical marker for circulating sex hormone concentrations. The weak-to-null associations between balding status and intraprostatic sex hormones reaffirm differences in organ-specific sex hormone metabolism, implying that other sex steroid hormone-related factors (eg, androgen receptor) play important roles in organ-specific androgenic actions, and that other overlapping pathways may be involved in associations between the two complex conditions.


Assuntos
Alopecia/sangue , Alopecia/diagnóstico , Hormônios Esteroides Gonadais/sangue , Folículo Piloso/metabolismo , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Alopecia/epidemiologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Seguimentos , Hormônios Esteroides Gonadais/metabolismo , Cabelo/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Neoplasias da Próstata/epidemiologia , Tórax/metabolismo
3.
Cancer Epidemiol Biomarkers Prev ; 26(11): 1660-1666, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28830872

RESUMO

Background: Sex hormones have been implicated in prostate carcinogenesis, yet epidemiologic studies have not provided substantiating evidence. We tested the hypothesis that circulating concentrations of sex steroid hormones reflect intraprostatic concentrations using serum and adjacent microscopically verified benign prostate tissue from prostate cancer cases.Methods: Incident localized prostate cancer cases scheduled for surgery were invited to participate. Consented participants completed surveys, and provided resected tissues and blood. Histologic assessment of the ends of fresh frozen tissue confirmed adjacent microscopically verified benign pathology. Sex steroid hormones in sera and tissues were extracted, chromatographically separated, and then quantitated by radioimmunoassays. Linear regression was used to account for variations in intraprostatic hormone concentrations by age, body mass index, race, and study site, and subsequently to assess relationships with serum hormone concentrations. Gleason score (from adjacent tumor tissue), race, and age were assessed as potential effect modifiers.Results: Circulating sex steroid hormone concentrations had low-to-moderate correlations with, and explained small proportions of variations in, intraprostatic sex steroid hormone concentrations. Androstane-3α,17ß-diol glucuronide (3α-diol G) explained the highest variance of tissue concentrations of 3α-diol G (linear regression r2 = 0.21), followed by serum testosterone and tissue dihydrotestosterone (r2 = 0.10), and then serum estrone and tissue estrone (r2 = 0.09). There was no effect modification by Gleason score, race, or age.Conclusions: Circulating concentrations of sex steroid hormones are poor surrogate measures of the intraprostatic hormonal milieu.Impact: The high exposure misclassification provided by circulating sex steroid hormone concentrations for intraprostatic levels may partly explain the lack of any consistent association of circulating hormones with prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(11); 1660-6. ©2017 AACR.


Assuntos
Hormônios Esteroides Gonadais/análise , Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Globulina de Ligação a Hormônio Sexual
4.
Am J Prev Med ; 53(3): 363-372, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28676254

RESUMO

INTRODUCTION: Colorectal cancer is a leading cause of cancer-related death in the U.S. Although screening reduces colorectal cancer incidence and mortality, screening rates among U.S. adults remain less than optimal, especially among disadvantaged populations. This study examined the efficacy of patient navigation to increase colonoscopy screening. STUDY DESIGN: RCT. SETTING/PARTICIPANTS: A total of 843 low-income adults, primarily Hispanic and non-Hispanic blacks, aged 50-75 years referred for colonoscopy at Boston Medical Center were randomized into the intervention (n=429) or control (n=427) groups. Participants were enrolled between September 2012 and December 2014, with analysis following through 2015. INTERVENTION: Two bilingual lay navigators provided individualized education and support to reduce patient barriers and facilitate colonoscopy completion. The intervention was delivered largely by telephone. MAIN OUTCOME MEASURE: Colonoscopy completion within 6 months of study enrollment. RESULTS: Colonoscopy completion was significantly higher for navigated patients (61.1%) than control group patients receiving usual care (53.2%, p=0.021). Based on regression analysis, the odds of completing a colonoscopy for navigated patients was one and a half times greater than for controls (95% CI=1.12, 2.03, p=0.007). There were no differences between navigated and control groups in regard to adequacy of bowel preparation (95.3% vs 97.3%, respectively). CONCLUSIONS: Navigation significantly improved colonoscopy screening completion among a racially diverse, low-income population. Results contribute to mounting evidence demonstrating the efficacy of patient navigation in increasing colorectal cancer screening. Screening can be further enhanced when navigation is combined with other evidence-based practices implemented in healthcare systems and the community.


Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Navegação de Pacientes/métodos , Centros Médicos Acadêmicos/estatística & dados numéricos , Idoso , Boston , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Incidência , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Sangue Oculto , Navegação de Pacientes/estatística & dados numéricos , Pobreza/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Encaminhamento e Consulta/estatística & dados numéricos , Autorrelato , Fatores Socioeconômicos
5.
Am J Epidemiol ; 186(12): 1352-1361, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28633309

RESUMO

The prevalence of fusions of the transmembrane protease, serine 2, gene (TMPRSS2) with the erythroblast transformation-specific-related gene (ERG), or TMPRSS2:ERG, in prostate cancer varies by race. However, such somatic aberration and its association with prognostic factors have neither been studied in a West African population nor been systematically reviewed in the context of racial differences. We used immunohistochemistry to assess oncoprotein encoded by the ERG gene as the established surrogate of ERG fusion genes among 262 prostate cancer biopsies from the Ghana Prostate Study (2004-2006). Poisson regression with robust variance estimation provided prevalence ratios and 95% confidence intervals of ERG expression in relation to patient characteristics. We found that 47 of 262 (18%) prostate cancers were ERG-positive, and being negative for ERG staining was associated with higher Gleason score. We further conducted a systematic review and meta-analysis of TMPRSS2:ERG fusions in relation to race, Gleason score, and tumor stage, combining results from Ghana with 40 additional studies. Meta-analysis showed the prevalence of TMPRSS2:ERG fusions in prostate cancer to be highest in men of European descent (49%), followed by men of Asian (27%) and then African (25%) descent. The lower prevalence of TMPRSS2:ERG fusions in men of African descent implies that alternative genomic mechanisms might explain the disproportionately high prostate cancer burden in such populations.


Assuntos
Fusão Gênica , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/genética , Serina Endopeptidases/genética , Idoso , Comorbidade , Grupos de Populações Continentais/estatística & dados numéricos , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prevalência , Neoplasias da Próstata/patologia , Regulador Transcricional ERG/genética
6.
Int J Cancer ; 139(11): 2467-73, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27537611

RESUMO

A small proportion of individuals infected with Epstein-Barr virus (EBV) develop nasopharyngeal carcinoma (NPC). Timing of initial exposure could alter immunological responses to primary EBV infection and explain variation in cancer risk later in life. We measured early life family structure as a proxy for the timing of primary EBV infection to examine whether earlier age at infection alters NPC risk. We utilized data from 480 NPC cases and 1,291 unaffected siblings from Taiwanese NPC multiplex families (≥ 2 family members with NPC, N = 2,921). Information on birth order within the family was derived from questionnaires. We utilized logistic regression models to examine the association between birth order and NPC, accounting for correlations between relatives. Within these high-risk families, older siblings had an elevated risk of NPC. Compared with being a first-born child, the risk (95% CIs) of NPC associated with a birth order of two, three, four and five or more was 1.00 (0.71, 1.40), 0.88 (0.62, 1.24), 0.74 (0.53, 1.05) and 0.60 (0.43, 0.82), respectively (P for trend = 0.002). We observed no associations between NPC risk and the number of younger siblings or cumulative infant-years exposure. These associations were not modified by underlying genetic predisposition or family size. We observed that early life family structure was important for NPC risk in NPC multiplex families, with older siblings having a greater risk of disease. Future studies focusing on more direct measures of the immune response to EBV in early childhood could elucidate the underlying mechanisms.


Assuntos
Ordem de Nascimento , Neoplasias Nasofaríngeas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/virologia , Prevalência , Risco , Irmãos , Taiwan/epidemiologia
7.
Nat Commun ; 7: 10979, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27052111

RESUMO

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.


Assuntos
Afro-Americanos , Epigênese Genética , Grupo com Ancestrais do Continente Europeu , Predisposição Genética para Doença , Padrões de Herança , Neoplasias da Próstata/genética , Acetilação , Atlas como Assunto , Linhagem Celular Tumoral , Loci Gênicos , Estudo de Associação Genômica Ampla , Histonas/genética , Histonas/metabolismo , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia
8.
J Natl Cancer Inst ; 108(7)2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26823525

RESUMO

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.


Assuntos
Afro-Americanos/genética , Cromossomos Humanos Par 8 , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Estados Unidos/epidemiologia
9.
Fertil Steril ; 104(4): 980-988, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26232746

RESUMO

OBJECTIVE: To examine the relationship of ovulation-stimulating drugs to risk of cancers other than breast and gynecologic malignancies. DESIGN: Retrospective cohort study, with additional follow-up since initial report. SETTING: Reproductive endocrinology practices. PATIENT(S): Among a cohort of 12,193 women evaluated for infertility between 1965 and 1988, a total of 9,892 women (81.1% of the eligible population) were followed through 2010, via passive and active (questionnaire) approaches. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Hazard ratios (HRs) and 95% confidence intervals (CIs) for various fertility treatment parameters for select cancers. RESULT(S): During 30.0 median years of follow-up (285,332 person-years), 91 colorectal cancers, 84 lung cancers, 55 thyroid cancers, and 70 melanomas were diagnosed among study subjects. Clomiphene citrate (CC), used by 38.1% of patients, was not associated with colorectal or lung cancer risks, but was related significantly to melanoma (HR = 1.95; 95% CI: 1.18-3.22), and non-significantly to thyroid cancer risks (HR = 1.57; 95% CI: 0.89-2.75). The highest melanoma risks were seen among those with the lowest drug exposure levels, but thyroid cancer risk was greatest among the heavily exposed patients (HR = 1.96; 95% CI: 0.92-4.17 for those receiving >2,250 mg). Clomiphene citrate-associated risks for thyroid cancer were somewhat higher among nulligravid, compared with gravid, women, but did not differ according to distinct causes of infertility. Gonadotropins, used by only 9.7% of subjects, were not related to risk of any of the assessed cancers. CONCLUSION(S): Our results provide support for continued monitoring of both melanoma and thyroid cancer risk among patients receiving fertility drugs.


Assuntos
Fármacos para a Fertilidade Feminina/uso terapêutico , Neoplasias/epidemiologia , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias Colorretais/epidemiologia , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Seguimentos , Neoplasias dos Genitais Femininos/epidemiologia , Humanos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/epidemiologia , Neoplasias Pulmonares/epidemiologia , Melanoma/epidemiologia , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/epidemiologia
10.
Hum Mol Genet ; 24(19): 5603-18, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26162851

RESUMO

Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10(-4)-5.6 × 10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Hispano-Americanos/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Mapeamento Cromossômico/métodos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Anotação de Sequência Molecular , Neoplasias da Próstata/etnologia , Locos de Características Quantitativas
11.
J Urol ; 192(3): 730-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24747091

RESUMO

PURPOSE: To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana. MATERIALS AND METHODS: We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent transrectal ultrasound guided biopsies. RESULTS: Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0 ng/ml. CONCLUSIONS: In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology.


Assuntos
Grupo com Ancestrais do Continente Africano , Neoplasias da Próstata/epidemiologia , Afro-Americanos , Idoso , Gana , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Antígeno Prostático Específico
12.
Cancer Epidemiol Biomarkers Prev ; 23(4): 584-93, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24700523

RESUMO

BACKGROUND: Although fertility drugs stimulate ovulation and raise estradiol levels, their effect on breast cancer risk remains unresolved. METHODS: An extended follow-up was conducted among a cohort of 12,193 women evaluated for infertility between 1965 and 1988 at five U.S. sites. Follow-up through 2010 was achieved for 9,892 women (81.1% of the eligible population) via passive as well as active (questionnaires) means. Cox regression determined HRs and 95% confidence intervals (CI) for fertility treatments adjusted for breast cancer risk factors and causes of infertility. RESULTS: During 30.0 median years of follow-up (285,332 person-years), 749 breast cancers were observed. Ever use of clomiphene citrate among 38.1% of patients was not associated with risk (HR = 1.05; 95% CI, 0.90-1.22 vs. never use). However, somewhat higher risks were seen for patients who received multiple cycles, with the risk for invasive cancers confirmed by medical records being significantly elevated (HR = 1.69; 95% CI, 1.17-2.46). This risk remained relatively unchanged after adjustment for causes of infertility and multiple breast cancer predictors. Gonadotropins, used by 9.6% of patients, mainly in conjunction with clomiphene, showed inconsistent associations with risk, although a significant relationship of use with invasive cancers was seen among women who remained nulligravid (HR = 1.98; 95% CI, 1.04-3.60). CONCLUSIONS: Although the increased breast cancer risk among nulligravid women associated with gonadotropins most likely reflects an effect of underlying causes of infertility, reasons for the elevated risk associated with multiple clomiphene cycles are less clear. IMPACT: Given our focus on a relatively young population, additional evaluation of long-term fertility drug effects on breast cancer is warranted.


Assuntos
Neoplasias da Mama/epidemiologia , Fármacos para a Fertilidade Feminina/administração & dosagem , Ovulação/efeitos dos fármacos , Adulto , Neoplasias da Mama/induzido quimicamente , Clomifeno/administração & dosagem , Clomifeno/efeitos adversos , Estudos de Coortes , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Humanos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
13.
Hum Genet ; 133(5): 509-21, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24185611

RESUMO

Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference. We conducted a genome-wide association study (GWAS) of prostate cancer in West African men in the Ghana Prostate Study. Association testing was performed using multivariable logistic regression adjusted for age and genetic ancestry for 474 prostate cancer cases and 458 population-based controls on the Illumina HumanOmni-5 Quad BeadChip. The most promising association was at 10p14 within an intron of a long non-coding RNA (lncRNA RP11-543F8.2) 360 kb centromeric of GATA3 (p = 1.29E-7). In sub-analyses, SNPs at 5q31.3 were associated with high Gleason score (≥7) cancers, the strongest of which was a missense SNP in PCDHA1 (rs34575154, p = 3.66E-8), and SNPs at Xq28 (rs985081, p = 8.66E-9) and 6q21 (rs2185710, p = 5.95E-8) were associated with low Gleason score (<7) cancers. We sought to validate our findings in silico in the African Ancestry Prostate Cancer GWAS Consortium, but only one SNP, at 10p14, replicated at p < 0.05. Of the 90 prostate cancer loci reported from studies of men of European, Asian or African-American ancestry, we were able to test 81 in the Ghana Prostate Study, and 10 of these replicated at p < 0.05. Further genetic studies of prostate cancer in West African men are needed to confirm our promising susceptibility loci.


Assuntos
Estudo de Associação Genômica Ampla , Neoplasias da Próstata/genética , África Ocidental , Idoso , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade
14.
Fertil Steril ; 100(6): 1660-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24011610

RESUMO

OBJECTIVE: To examine the relationship of ovulation-inducing drugs and ovarian cancer. DESIGN: Retrospective cohort study, with additional follow-up since initial report. SETTING: Five large reproductive endocrinology practices. PATIENT(S): In a retrospective cohort of 9,825 women evaluated for infertility at five clinical sites in the United States between 1965 and 1988 with follow-up through 2010, we examined the relationship of ovulation-inducing drugs and ovarian cancer (n = 85). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Hazard rate ratios (RR) and 95% confidence intervals (CI) for ovarian cancer. RESULT(S): Among women evaluated for infertility, there was no association of ovarian cancer risk with ever use of clomiphene citrate (CC) (adjusted RR 1.34, 95% CI 0.86-2.07) or gonadotropins (RR 1.00, 95% CI 0.48-2.08) and no evidence that any of several more detailed subgroups of usage were related to an increased risk with one exception: women who used CC and remained nulligravid did demonstrate much higher risks than those who successfully conceived compared with nonusers (respectively, RR 3.63, 95% CI 1.36-9.72 vs. RR 0.88, 95% CI 0.47-1.63). CONCLUSION(S): Our overall results were reassuring and consistent with other studies. A reason for an association between CC use and ovarian cancer among persistently nulligravid women remains to be determined. Given the large and increasing number of women treated with ovulation-inducing drugs, the increased risk of ovarian cancer among the subset of women who remained nulligravid should be further monitored.


Assuntos
Clomifeno/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Gonadotropinas/administração & dosagem , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/terapia , Neoplasias Ovarianas/epidemiologia , Indução da Ovulação/estatística & dados numéricos , Adulto , Causalidade , Estudos de Coortes , Comorbidade , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Estados Unidos/epidemiologia
15.
Hum Reprod ; 28(10): 2813-21, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23943795

RESUMO

STUDY QUESTION: Do fertility drugs influence the subsequent risk of endometrial cancer in a manner that is independent of other risk predictors, such as parity? SUMMARY ANSWER: In this follow-up of a large cohort of women evaluated for infertility and for whom information was captured on fertility drugs, indications for usage and other risk factors that might influence cancer risk, we found no evidence for a substantial relationship between fertility drug use and endometrial cancer risk. WHAT IS ALREADY KNOWN: Although the hormonal etiology of endometrial cancer has been well established, it remains unclear whether the use of fertility drugs has an influence on risk. Results regarding the effects of fertility drugs on endometrial cancer risk have been inconsistent, although several studies have shown some evidence for possible increases in risk. The relationship is of particular interest given that clomiphene, a commonly prescribed drug, is a selective estrogen receptor modulator, with chemical properties similar to tamoxifen, another drug linked to an increase in endometrial cancer risk. STUDY DESIGN, SIZE, DURATION: In a retrospective cohort of 12 193 women evaluated for infertility between 1965 and 1988 at five US sites, follow-up was pursued through 2010 via both passive as well as active (questionnaire) means. PARTICIPANTS, SETTING, METHODS: Among the 9832 subjects for whom follow-up was allowed and achieved, 259 346 at-risk person-years (i.e. prior to hysterectomy) were accrued, and 118 invasive endometrial cancers identified. Cox regression determined hazard ratios (HRs) and 95% confidence intervals (CIs) for fertility treatments adjusted for endometrial cancer risk factors and causes of infertility. MAIN RESULTS AND THE ROLE OF CHANCE: Although we observed slight increases in endometrial cancer risk associated with clomiphene (HR = 1.39, 95% CI: 0.96-2.01) and the less commonly prescribed gonadotrophins (1.34, 0.76-2.37), there were no convincing relationships of risk with either cycles of use or cumulative exposures for either drug. A statistically significant risk associated with the use of clomiphene among women who began use at younger ages (<30) (1.93, 1.24-3.00) may have reflected indications for drug usage rather than the effect of the drug itself. Women who received clomiphene followed by gonadotrophins were at a non-significantly elevated risk (1.77, 0.98-3.19). LIMITATIONS, REASONS FOR CAUTION: Like most studies of endometrial cancer, we were limited by sample sizes, particularly for evaluating subgroup associations. We were also unable to follow all women and were not able to obtain complete risk factor information (including hysterectomy status) for the entire cohort. WIDER IMPLICATIONS OF THE FINDINGS: Although we found no support for a relationship between fertility drugs and endometrial cancer risk, the association should continue to be monitored given that our study population was still young and had not yet reached the age of peak endometrial cancer incidence. STUDY FUNDING/COMPETING INTEREST(S): This project was supported in part by funds from the intramural research program of the National Cancer Institute, National Institutes of Health. None of the authors has any conflicting interests to declare.


Assuntos
Neoplasias do Endométrio/induzido quimicamente , Fármacos para a Fertilidade Feminina/efeitos adversos , Clomifeno/efeitos adversos , Estudos de Coortes , Feminino , Seguimentos , Humanos , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
16.
BMC Cancer ; 12: 468, 2012 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-23057767

RESUMO

BACKGROUND: Genetic variants in inflammation-related genes have been associated with biliary stones and biliary tract cancers in previous studies. METHODS: To follow-up on these findings, we examined 35 single nucleotide polymorphism (SNPs) in 5 genes related to inflammation (IL8, NFKBIL, RNASEL, TNF, and VEGFA) in 456 participants with incident biliary tract cancer cases (262 gallbladder, 141 extrahepatic bile duct, 53 ampulla of Vater), 982 participants with biliary stones, and 860 healthy controls in a population-based case-control study in Shanghai, China. RESULTS: Suggestive associations were observed for SNPs in VEGFA with biliary stones, IL8 with gallbladder and ampulla of Vater cancers, and RNASEL with ampulla of Vater cancer (false discovery rate≤0.2). CONCLUSION: These findings provide additional support for the role of inflammation in biliary stones and biliary tract cancer risk and need further validation.


Assuntos
Neoplasias do Sistema Biliar/genética , Cálculos Biliares/genética , Inflamação/genética , Idoso , Estudos de Casos e Controles , China , Endorribonucleases/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-8/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética
17.
Prev Med ; 52(6): 452-5, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21497619

RESUMO

OBJECTIVE: The aim of the study was to increase participation in cervical cancer screening of under-screened women living in the Mississippi Delta, a U.S. population at high risk for cervical cancer. METHODS: We conducted a door-to-door feasibility study of women living in the Mississippi Delta to increase participation in cervical cancer screening in 2009-10. Women (n=119) aged 26-65 years who had not been screened in last 3 years or more, were not pregnant, and had a cervix were offered a cost-free choice: clinic-based Pap testing or home self-collection with HPV DNA testing. RESULTS: Seventy-seven women (64.7%) chose self-collection with HPV testing, of which sixty-two (80.5%) returned their self-collected specimen. By comparison, 42 women (35.3%) chose Pap testing, of which 17 (40.5%) attended their clinic appointment. Thus there was an almost 4-fold greater participation of under-screened women in self-collection with HPV testing than in free Pap testing (78.4% vs. 21.5%). CONCLUSIONS: We found that offering self-collection will increase participation in cervical cancer screening among under-screened populations living in the Mississippi Delta. Based on these preliminary results, we suggest that self-collection with HPV DNA testing might complement current Pap testing programs to reach under-screened populations of women, such as those living in the Mississippi Delta.


Assuntos
Detecção Precoce de Câncer/métodos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/estatística & dados numéricos , Adulto , Idoso , Relações Comunidade-Instituição , Estudos de Viabilidade , Feminino , Humanos , Programas de Rastreamento , Área Carente de Assistência Médica , Pessoa de Meia-Idade , Mississippi , Papillomaviridae/isolamento & purificação , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/prevenção & controle
18.
Cancer Epidemiol Biomarkers Prev ; 19(4): 932-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20332275

RESUMO

BACKGROUND: Epidemiologic data on serum melatonin, a marker of circadian rhythms, and cancer are sparse due largely to the lack of reliable assays with high sensitivity to detect relatively low melatonin levels in serum collected during daylight, as commonly available in most epidemiologic studies. METHODS: To help expand epidemiologic research on melatonin, we assessed the reproducibility and refined a currently available melatonin RIA, and evaluated its application to epidemiologic investigations by characterizing melatonin levels in serum, urine, and/or plasma in 135 men from several ethnic groups. RESULTS: Reproducibility was high for the standard 1.0-mL serum [mean coefficient of variation (CV), 6.9%; intraclass correlation coefficient (ICC), 97.4%; n = 2 serum pools in triplicate] and urine-based (mean CV, 3.5%; ICC, 99.9%) assays. Reproducibility for the 0.5-mL refined-serum assay was equally good (mean CV, 6.6%; ICC, 99.0%). There was a positive correlation between morning serum melatonin and 6-sulfatoxymelatonin in 24-hour urine (r = 0.46; P = 0.008; n = 49 subjects). Melatonin levels in serum-plasma pairs had a high correlation (r = 0.97; P < 1x10(-4); n = 20 pairs). Morning serum melatonin levels were five times higher than those from the afternoon (before 9 a.m. mean, 11.0 pg/mL, versus after 11 a.m. mean, 2.0 pg/mL). Chinese men had lower melatonin levels (mean, 3.4 pg/mL), whereas Caucasian, African-American, and Ghanaian men had similar levels (mean, 6.7-8.6 pg/mL). CONCLUSIONS: These results suggest that melatonin can be detected reliably in serum samples collected in epidemiologic studies in various racial groups. IMPACT: With improved assays, it may be possible to investigate the role of melatonin and the emerging circadian rhythm hypothesis in cancer etiology in epidemiologic studies.


Assuntos
Melatonina/sangue , Melatonina/urina , Radioimunoensaio/métodos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Ritmo Circadiano/fisiologia , Humanos , Masculino , Neoplasias/sangue , Neoplasias/epidemiologia , Neoplasias/urina , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Cancer Epidemiol Biomarkers Prev ; 19(3): 787-93, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20200439

RESUMO

Biliary tract cancers, encompassing cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, are rare but highly fatal. Gallstones represent the major risk factor for biliary tract cancer, and share with gallbladder cancer a female predominance and an association with reproductive factors and obesity. Although estrogens have been implicated in earlier studies of gallbladder cancer, there are no data on the role of androgens. Because intracellular androgen activity is mediated through the androgen receptor (AR), we examined associations between AR CAG repeat length [(CAG)(n)] and the risk of biliary tract cancers and stones in a population-based study of 331 incident cancer cases, 837 gallstone cases, and 750 controls from Shanghai, China, where the incidence rates for biliary tract cancer are rising sharply. Men with (CAG)(n) >24 had a significant 2-fold risk of gallbladder cancer [odds ratio (OR), 2.00; 95% confidence interval (CI), 1.07-3.73], relative to those with (CAG)(n) < or = 22. In contrast, women with (CAG)(n) >24 had reduced gallbladder cancer risk (OR, 0.69; 95% CI, 0.43-1.09) relative to those with (CAG)(n) < or = 22; P interaction sex = 0.01, which was most pronounced for women ages 68 to 74 (OR, 0.48; 95% CI, 0.25-0.93; P interaction age = 0.02). No associations were found for bile duct cancer or gallstones. Reasons for the heterogeneity of genetic effects by gender and age are unclear but may reflect an interplay between AR and the levels of androgen as well as estrogen in men and older women. Further studies are needed to confirm these findings and clarify the mechanisms involved.


Assuntos
Neoplasias do Sistema Biliar/genética , Cálculos Biliares/genética , Predisposição Genética para Doença , Receptores Androgênicos/genética , Repetições de Trinucleotídeos/genética , Adulto , Idoso , Neoplasias do Sistema Biliar/epidemiologia , China/epidemiologia , Feminino , Cálculos Biliares/epidemiologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco
20.
Cancer Res ; 68(15): 6442-52, 2008 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-18676870

RESUMO

To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003) and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer.


Assuntos
Neoplasias do Sistema Biliar/genética , Inflamação/genética , Vigilância da População , Neoplasias do Sistema Biliar/epidemiologia , China , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco
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