Prostate Cancer Studies

前列腺癌研究

• 批准号: 10918986
• 负责人: Demetrius Albanes
• 金额: $ 37.09万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10918986
• 关键词: 8q24; Africa; African; Age; Androgen Metabolism; Androgens; Biochemical; Biological; Biological Assay; Biological Markers; Blood; Burkitt Lymphoma; Case Series; Central obesity; China; Cities; Classification; Clinical; Collection; Colorectal; Consent; Data; Databases; Diagnosis; Dietary Factors; Dietary Practices; Epidemiology; Ethnic Population; Fasting; Freezing; Fresh Tissue; Gene Expression; Genes; Genetic; Genetic Markers; Genotype; Ghana; Health; Hormonal; Hormonal Carcinogenesis; Hormones; Human; Human Genetics; Insulin; Insulin-Like Growth Factor I; Interview; Isoflavones; Life Style; Link; Low-Density Lipoproteins; Lung; Malaria; Malignant neoplasm of prostate; Manuscripts; Maps; Medicare; Meta-Analysis; Methodological Studies; Molecular; Molecular Genetics; Nature; Nested Case-Control Study; Non-Steroidal Anti-Inflammatory Agents; Nutritional; Obesity; Outcome; Ovarian; Pathway interactions; Pharmaceutical Preparations; Population; Predisposition; Prevalence; Prostate; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Prostatic Diseases; Publishing; Questionnaires; Recurrence; Research; Resources; Risk; Risk Assessment; Risk Factors; Risk Marker; Role; Sampling; Series; Serum; Stage at Diagnosis; Stains; Study Subject; Surveys; TMPRSS2 gene; Techniques; Testosterone; Time; Tissue Banks; Tissue Microarray; Tissue Sample; Tissues; Tumor Markers; Variant; androgenic; cancer risk; cancer type; candidate identification; clinical practice; clinically relevant; cohort; design; dietary; follow-up; genetic risk factor; genetic variant; genome wide association study; indexing; insight; men; metabolic profile; mortality; multi-racial; multidisciplinary; novel; population based; population survey; prostate cancer risk; prostate carcinogenesis; racial difference; racial population; recruit; resistance gene; soy; tumor; western diet

In Ghana, Africa, we have conducted a population-based survey of men to assess the population prevalence of prostatic disease (CAS ID:01130). We have also collected consented into the study a clinical series of men diagnosed with prostate cancer. This dynamic epidemiologic design of a population survey combined with a larger case series, is enabling us to assess the burden of prostate cancer in African men as well as assess risk factors associated with prostate cancer in an important and understudied population. Biological samples collected from the 1,038 healthy men in the population survey component will allow us to establish the nutritional, hormonal, and genetic profiles of African men. In addition, linking interview data from these 1,038 healthy subjects with biomarkers will produce insights into whether westernization in African men is associated with an adverse metabolic profile (obesity; abdominal obesity; higher levels of insulin, low-density lipoprotein, and insulin-like growth factor I), which has been associated with excess prostate cancer risk. The additional 677 prostate cancer cases that we recruited through the clinical component has enabled us to conduct a genome wide association study (GWAS) of prostate cancer in this unique population (published in Human Genetics). In addition, we have sequenced the 8q24 region and identified several novel variants (published in Prostate) as well contributed to a pooled fine-mapping study of this region in African Men (published in JNCI) and an imputation and subset based meta-analysis of chr5p15.33 across multiple cancer types (published in Human Molecular Genetics). We have also contributed data to multi-racial GWAS and have identified 23 novel genetic (SNP) associations with prostate cancer (published in Nature Genetics). We have recently contributed to an integrative analysis to identify candidate functional SNPs at prostate cancer susceptibility regions of the geonome (published in Human Molecular Genetics). We are now extending this GWAS effort to include additional cases and controls that were recruited for this study. We are also using the population component of the Ghana Prostate Study to assess the prevalence of malaria-resistance genes with a view to uncovering the genetic risk factors of Burkitt lymphoma in Africa. We are assessing whether IFNL4 is also prominent in African men by genotyping the IFNL4 variant in 350 population-based controls in the Ghana Prostate Study. We are also assessing whether this variant can be imputed using the existing GWAS data. We are assessing whether IFNL4 is associated with age and/or stage at diagnosis of prostate cancer in the Ghana Prostate Study. We are also currently assessing the prevalence of TMPRSS2-ERG fusions in prostate cancer tissues of these African prostate cancer cases (manuscript being drafted). We have also begun analyses of questionnaire components of this study to further elucidate associations of prostate cancer in this novel population. We have conducted a multidisciplinary study in China to assess risk factors for prostate cancer in a low-risk population in order to understand more clearly the reasons for the large racial differences in prostate cancer risk (CAS ID:01140). That study involved the collection of multiple biologic samples, with a primary aim of assessing risk factors and how westernization influences the risk of prostate cancer. The study also involved the collection of tissue samples from prostate cancer tumors to permit precise tumor classification as well as assays of tumor biomarkers, in some cases using newly developed tissue microarray techniques. In addition to specific dietary factors, dietary patterns will be identified and compared with those of controls to evaluate whether a western-style diet in China is related to excess prostate cancer risk. The study is also assessing biological correlates of westernization to look for potential biological links between westernization and excess prostate cancer risk. Data on genotypes and circulating levels of hormones provide a unique opportunity to investigate the interrelationships between serum hormones and genetic variants to gain insights into the functional significance of these genetic markers. In another study of prostate cancer in 15 cities in China, we are assessing the role of soy in prostate cancer by developing a dietary isoflavone index. In addition, several nested case-control studies in large cohorts, including Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, the SEER-Medicare database, total Medicare, and Clinical Practice Research Datalink (CPRD) we are assessing the relationships of hormone-related factors with subsequent risks of prostate cancer and prostate cancer-specific mortality. A methodologic study is currently underway to evaluate whether circulating levels of androgens reflect intraprostatic androgenicity, a key issue in hormonal carcinogenesis of the prostate (CAS ID:01072). This methodologic study has collected samples of fasting blood and snap-frozen fresh tissue (over 3,000 pieces) from 600 study subjects in three racial/ethnic groups. Data from this study will provide a unique opportunity to investigate the interrelationships among serum and tissue hormones and variants in genes involved in the androgen metabolism pathways to provide critical data for determining the functional significance of these genetic markers. The collection of tissue samples also will provide a unique opportunity for gene expression studies. This manuscript is currently being drafted.In continuing the theme of hormonal perturbations in relation to prostate cancer, we are also using a large health database to assess whether testosterone replacement medications are associated with prostate cancer risk (CAS ID: 10667). For more accurate and detailed follow up in PLCO to enable prostate recurrence analyses and analyses of outcomes post-diagnosis in this resource, we are currently extending the follow-up time beyond the first year post-diagnosis to capture all clinically relevant data (CAS ID: 10515). Biochemical recurrence is being assessed in relation to tissue IHC stains.Lastly, we are using data from AARP to investigate the association of NSAID use and subsequent risk of cancer, including prostate cancer (CAS ID: 10547), the manuscript of which is currently under review.

项目成果

Relationships between Circulating and Intraprostatic Sex Steroid Hormone Concentrations.

• DOI: 10.1158/1055-9965.epi-17-0215
• 发表时间: 2017-11
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Cook MB;Stanczyk FZ;Wood SN;Pfeiffer RM;Hafi M;Veneroso CC;Lynch B;Falk RT;Zhou CK;Niwa S;Emanuel E;Gao YT;Hemstreet GP;Zolfghari L;Carroll PR;Manyak MJ;Sesterhann IA;Levine PH;Hsing AW
• 通讯作者: Hsing AW

Circulating and intraprostatic sex steroid hormonal profiles in relation to male pattern baldness and chest hair density among men diagnosed with localized prostate cancers.

循环和前列腺内性类固醇激素分布与诊断患有局限性前列腺癌的男性的男性型秃发和胸毛密度有关。

• DOI: 10.1002/pros.23433
• 发表时间: 2017
• 期刊: The Prostate
• 作者: Zhou,CindyKe;Stanczyk,FrankZ;Hafi,Muhannad;Veneroso,CarmelaC;Lynch,Barlow;Falk,RoniT;Niwa,Shelley;Emanuel,Eric;Gao,Yu-Tang;Hemstreet,GeorgeP;Zolfghari,Ladan;Carroll,PeterR;Manyak,MichaelJ;Sesterhenn,IsabellA;Levine,Pau
• 通讯作者: Levine,Pau

High prevalence of screen detected prostate cancer in West Africans: implications for racial disparity of prostate cancer.

• DOI: 10.1016/j.juro.2014.04.017
• 发表时间: 2014-09
• 期刊: JOURNAL OF UROLOGY
• 影响因子: 6.6
• 作者: Hsing, Ann W.;Yeboah, Edward;Biritwum, Richard;Tettey, Yao;De Marzo, Angelo M.;Adjei, Andrew;Netto, George J.;Yu, Kai;Li, Yan;Chokkalingam, Anand P.;Chu, Lisa W.;Chia, David;Partin, Alan;Thompson, Ian M.;Quraishi, Sabah M.;Niwa, Shelley;Tarone, Robert;Hoover, Robert N.
• 通讯作者: Hoover, Robert N.

Prediagnostic circulating anti-Müllerian hormone concentrations are not associated with prostate cancer risk.

诊断性循环抗肿瘤激素浓度与前列腺癌风险无关。

• DOI: 10.1158/1055-9965.epi-14-0803
• 发表时间: 2014-11
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Sklavos MM;Zhou CK;Pinto LA;Cook MB
• 通讯作者: Cook MB

Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex hormone-binding globulin.

• DOI: 10.1158/1055-9965.epi-10-0101
• 发表时间: 2010-07
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Chu LW;Meyer TE;Li Q;Menashe I;Yu K;Rosenberg PS;Huang WY;Quraishi SM;Kaaks R;Weiss JM;Hayes RB;Chanock SJ;Hsing AW
• 通讯作者: Hsing AW