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Mucci, Lorelei

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Lorelei

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Mucci, Lorelei
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    CanWalk: a feasibility study with embedded randomised controlled trial pilot of a walking intervention for people with recurrent or metastatic cancer
    (BMJ Publishing Group, 2017) Tsianakas, Vicki; Harris, Jenny; Ream, Emma; Van Hemelrijck, Mieke; Purushotham, Arnie; Mucci, Lorelei; Green, James S A; Fewster, Jacquetta; Armes, Jo
    Objectives: Walking is an adaptable, inexpensive and accessible form of physical activity. However, its impact on quality of life (QoL) and symptom severity in people with advanced cancer is unknown. This study aimed to assess the feasibility and acceptability of a randomised controlled trial (RCT) of a community-based walking intervention to enhance QoL in people with recurrent/metastatic cancer. Design: We used a mixed-methods design comprising a 2-centre RCT and nested qualitative interviews. Participants: Patients with advanced breast, prostate, gynaecological or haematological cancers randomised 1:1 between intervention and usual care. Intervention The intervention comprised Macmillan's ‘Move More’ information, a short motivational interview with a recommendation to walk for at least 30 min on alternate days and attend a volunteer-led group walk weekly. Outcomes We assessed feasibility and acceptability of the intervention and RCT by evaluating study processes (rates of recruitment, consent, retention, adherence and adverse events), and using end-of-study questionnaires and qualitative interviews. Patient-reported outcome measures (PROMs) assessing QoL, activity, fatigue, mood and self-efficacy were completed at baseline and 6, 12 and 24 weeks. Results: We recruited 42 (38%) eligible participants. Recruitment was lower than anticipated (goal n=60), the most commonly reported reason being unable to commit to walking groups (n=19). Randomisation procedures worked well with groups evenly matched for age, sex and activity. By week 24, there was a 45% attrition rate. Most PROMs while acceptable were not sensitive to change and did not capture key benefits. Conclusions: The intervention was acceptable, well tolerated and the study design was judged acceptable and feasible. Results are encouraging and demonstrate that exercise was popular and conveyed benefit to participants. Consequently, an effectiveness RCT is warranted, with some modifications to the intervention to include greater tailoring and more appropriate PROMs selected. Trial registration number ISRCTN42072606.
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    Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility
    (Nature Publishing Group UK, 2017) Sud, Amit; Thomsen, Hauke; Law, Philip J.; Försti, Asta; Filho, Miguel Inacio da Silva; Holroyd, Amy; Broderick, Peter; Orlando, Giulia; Lenive, Oleg; Wright, Lauren; Cooke, Rosie; Easton, Douglas; Pharoah, Paul; Dunning, Alison; Peto, Julian; Canzian, Federico; Eeles, Rosalind; Kote-Jarai, ZSofia; Muir, Kenneth; Pashayan, Nora; Henderson, Brian E.; Haiman, Christopher A.; Benlloch, Sara; Schumacher, Fredrick R.; Olama, Ali Amin Al; Berndt, Sonja I.; Conti, David V.; Wiklund, Fredrik; Chanock, Stephen; Stevens, Victoria L.; Tangen, Catherine M.; Batra, Jyotsna; Clements, Judith; Gronberg, Henrik; Schleutker, Johanna; Albanes, Demetrius; Weinstein, Stephanie; Wolk, Alicja; West, Catharine; Mucci, Lorelei; Cancel-Tassin, Géraldine; Koutros, Stella; Sorensen, Karina Dalsgaard; Maehle, Lovise; Neal, David E.; Travis, Ruth C.; Hamilton, Robert J.; Ingles, Sue Ann; Rosenstein, Barry; Lu, Yong-Jie; Giles, Graham G.; Kibel, Adam S.; Vega, Ana; Kogevinas, Manolis; Penney, Kathryn; Park, Jong Y.; Stanford, Janet L.; Cybulski, Cezary; Nordestgaard, Børge G.; Brenner, Hermann; Maier, Christiane; Kim, Jeri; John, Esther M.; Teixeira, Manuel R.; Neuhausen, Susan L.; De Ruyck, Kim; Razack, Azad; Newcomb, Lisa F.; Lessel, Davor; Kaneva, Radka; Usmani, Nawaid; Claessens, Frank; Townsend, Paul A.; Dominguez, Manuela Gago; Roobol, Monique J.; Menegaux, Florence; Hoffmann, Per; Nöthen, Markus M.; Jöckel, Karl-Heinz; Strandmann, Elke Pogge von; Lightfoot, Tracy; Kane, Eleanor; Roman, Eve; Lake, Annette; Montgomery, Dorothy; Jarrett, Ruth F.; Swerdlow, Anthony J.; Engert, Andreas; Orr, Nick; Hemminki, Kari; Houlston, Richard S.
    Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10−8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10−17), 6q23.3 (rs6928977, P = 4.62 × 10−11), 10p14 (rs3781093, P = 9.49 × 10−13), 13q34 (rs112998813, P = 4.58 × 10−8) and 16p13.13 (rs34972832, P = 2.12 × 10−8). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.
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    Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
    (Nature Publishing Group UK, 2018) Dadaev, Tokhir; Saunders, Edward J.; Newcombe, Paul J.; Anokian, Ezequiel; Leongamornlert, Daniel A.; Brook, Mark N.; Cieza-Borrella, Clara; Mijuskovic, Martina; Wakerell, Sarah; Olama, Ali Amin Al; Schumacher, Fredrick R.; Berndt, Sonja I.; Benlloch, Sara; Ahmed, Mahbubl; Goh, Chee; Sheng, Xin; Zhang, Zhuo; Muir, Kenneth; Govindasami, Koveela; Lophatananon, Artitaya; Stevens, Victoria L.; Gapstur, Susan M.; Carter, Brian D.; Tangen, Catherine M.; Goodman, Phyllis; Thompson, Ian M.; Batra, Jyotsna; Chambers, Suzanne; Moya, Leire; Clements, Judith; Horvath, Lisa; Tilley, Wayne; Risbridger, Gail; Gronberg, Henrik; Aly, Markus; Nordström, Tobias; Pharoah, Paul; Pashayan, Nora; Schleutker, Johanna; Tammela, Teuvo L. J.; Sipeky, Csilla; Auvinen, Anssi; Albanes, Demetrius; Weinstein, Stephanie; Wolk, Alicja; Hakansson, Niclas; West, Catharine; Dunning, Alison M.; Burnet, Neil; Mucci, Lorelei; Giovannucci, Edward; Andriole, Gerald; Cussenot, Olivier; Cancel-Tassin, Géraldine; Koutros, Stella; Freeman, Laura E. Beane; Sorensen, Karina Dalsgaard; Orntoft, Torben Falck; Borre, Michael; Maehle, Lovise; Grindedal, Eli Marie; Neal, David E.; Donovan, Jenny L.; Hamdy, Freddie C.; Martin, Richard M.; Travis, Ruth C.; Key, Tim J.; Hamilton, Robert J.; Fleshner, Neil E.; Finelli, Antonio; Ingles, Sue Ann; Stern, Mariana C.; Rosenstein, Barry; Kerns, Sarah; Ostrer, Harry; Lu, Yong-Jie; Zhang, Hong-Wei; Feng, Ninghan; Mao, Xueying; Guo, Xin; Wang, Guomin; Sun, Zan; Giles, Graham G.; Southey, Melissa C.; MacInnis, Robert J.; FitzGerald, Liesel M.; Kibel, Adam S.; Drake, Bettina F.; Vega, Ana; Gómez-Caamaño, Antonio; Fachal, Laura; Szulkin, Robert; Eklund, Martin; Kogevinas, Manolis; Llorca, Javier; Castaño-Vinyals, Gemma; Penney, Kathryn; Stampfer, Meir; Park, Jong Y.; Sellers, Thomas A.; Lin, Hui-Yi; Stanford, Janet L.; Cybulski, Cezary; Wokolorczyk, Dominika; Lubinski, Jan; Ostrander, Elaine A.; Geybels, Milan S.; Nordestgaard, Børge G.; Nielsen, Sune F.; Weisher, Maren; Bisbjerg, Rasmus; Røder, Martin Andreas; Iversen, Peter; Brenner, Hermann; Cuk, Katarina; Holleczek, Bernd; Maier, Christiane; Luedeke, Manuel; Schnoeller, Thomas; Kim, Jeri; Logothetis, Christopher J.; John, Esther M.; Teixeira, Manuel R.; Paulo, Paula; Cardoso, Marta; Neuhausen, Susan L.; Steele, Linda; Ding, Yuan Chun; De Ruyck, Kim; De Meerleer, Gert; Ost, Piet; Razack, Azad; Lim, Jasmine; Teo, Soo-Hwang; Lin, Daniel W.; Newcomb, Lisa F.; Lessel, Davor; Gamulin, Marija; Kulis, Tomislav; Kaneva, Radka; Usmani, Nawaid; Slavov, Chavdar; Mitev, Vanio; Parliament, Matthew; Singhal, Sandeep; Claessens, Frank; Joniau, Steven; Van den Broeck, Thomas; Larkin, Samantha; Townsend, Paul A.; Aukim-Hastie, Claire; Gago-Dominguez, Manuela; Castelao, Jose Esteban; Martinez, Maria Elena; Roobol, Monique J.; Jenster, Guido; van Schaik, Ron H. N.; Menegaux, Florence; Truong, Thérèse; Koudou, Yves Akoli; Xu, Jianfeng; Khaw, Kay-Tee; Cannon-Albright, Lisa; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; Lindstrom, Sara; Turman, Constance; Ma, Jing; Hunter, David; Riboli, Elio; Siddiq, Afshan; Canzian, Federico; Kolonel, Laurence N.; Le Marchand, Loic; Hoover, Robert N.; Machiela, Mitchell J.; Kraft, Phillip; Cook, Margaret; Thwaites, Alison; Guy, Michelle; Whitmore, Ian; Morgan, Angela; Fisher, Cyril; Hazel, Steve; Livni, Naomi; Spurdle, Amanda; Srinivasan, Srilakshmi; Kedda, Mary-Anne; Aitken, Joanne; Gardiner, Robert; Hayes, Vanessa; Butler, Lisa; Taylor, Renea; Yeadon, Trina; Eckert, Allison; Saunders, Pamela; Haynes, Anne-Maree; Papargiris, Melissa; Kujala, Paula; Talala, Kirsi; Murtola, Teemu; Taari, Kimmo; Dearnaley, David; Barnett, Gill; Bentzen, Søren; Elliott, Rebecca; Ranu, Hardeep; Hicks, Belynda; Vogt, Aurelie; Hutchinson, Amy; Cox, Angela; Davis, Michael; Brown, Paul; George, Anne; Marsden, Gemma; Lane, Athene; Lewis, Sarah J.; Berry, Clare; Kulkarni, Girish S.; Toi, Ants; Evans, Andrew; Zlotta, Alexandre R.; van der Kwast, Theodorus H.; Imai, Takashi; Saito, Shiro; Marzec, Jacek; Cao, Guangwen; Lin, Ji; Ling, Jin; Li, Meiling; Zhao, Shan-Chao; Ren, Guoping; Yu, Yongwei; Wu, Yudong; Wu, Ji; Zhou, Bo; Zhang, Yangling; Li, Jie; He, Weiyang; Guo, Jianming; Pedersen, John; Hopper, John L.; Milne, Roger; Klim, Aleksandra; Carballo, Ana; Lobato-Busto, Ramón; Peleteiro, Paula; Calvo, Patricia; Aguado, Miguel; Ruiz-Dominguez, José Manuel; Cecchini, Lluís; Mengual, Lourdes; Alcaraz, Antonio; Bustamante, Mariona; Gracia-Lavedan, Esther; Dierssen-Sotos, Trinidad; Gomez-Acebo, Ines; Pow-Sang, Julio; Park, Hyun; Zachariah, Babu; Kluzniak, Wojciech; Kolb, Suzanne; Klarskov, Peter; Stegmaier, Christa; Vogel, Walther; Herkommer, Kathleen; Bohnert, Philipp; Maia, Sofia; Silva, Maria P.; De Langhe, Sofie; Thierens, Hubert; Tan, Meng H.; Ong, Aik T.; Kastelan, Zeljko; Popov, Elenko; Kachakova, Darina; Mitkova, Atanaska; Vlahova, Aleksandrina; Dikov, Tihomir; Christova, Svetlana; Carracedo, Angel; Bangma, Christopher; Schroder, F. H.; Cenee, Sylvie; Tretarre, Brigitte; Rebillard, Xavier; Mulot, Claire; Sanchez, Marie; Adolfsson, Jan; Stattin, Par; Johansson, Jan-Erik; Cavalli-Bjoerkman, Carin; Karlsson, Ami; Broms, Michael; Wu, Huihai; Tillmans, Lori; Riska, Shaun; Freedman, Matthew; Wiklund, Fredrik; Chanock, Stephen; Henderson, Brian E.; Easton, Douglas F.; Haiman, Christopher A.; Eeles, Rosalind A.; Conti, David V.; Kote-Jarai, Zsofia
    Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
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    Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer
    (Nature Publishing Group UK, 2017) Tyekucheva, Svitlana; Bowden, Michaela; Bango, Clyde; Giunchi, Francesca; Huang, Ying; Zhou, Chensheng; Bondi, Arrigo; Lis, Rosina; Van Hemelrijck, Mieke; Andrén, Ove; Andersson, Sven-Olof; Watson, R. William; Pennington, Stephen; Finn, Stephen P.; Martin, Neil; Stampfer, Meir; Parmigiani, Giovanni; Penney, Kathryn; Fiorentino, Michelangelo; Mucci, Lorelei; Loda, Massimo
    While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and cells in the cancer microenvironment are co-dependent and co-evolve. Few human studies to date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate epithelial tissue and compared it to non-transformed and neoplastic low-grade and high-grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma. Whereas benign epithelium in prostates with and without tumor were similar in gene expression space, stroma away from tumor was significantly different from that in prostates without cancer. A stromal gene signature reflecting bone remodeling and immune-related pathways was upregulated in high compared to low-Gleason grade cases. In validation data, the signature discriminated cases that developed metastasis from those that did not. These data suggest that the microenvironment may influence prostate cancer initiation, maintenance, and metastatic progression.
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    Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia
    (Nature Publishing Group UK, 2018) Vijayakrishnan, Jayaram; Studd, James; Broderick, Peter; Kinnersley, Ben; Holroyd, Amy; Law, Philip J.; Kumar, Rajiv; Allan, James M.; Harrison, Christine J.; Moorman, Anthony V.; Vora, Ajay; Roman, Eve; Rachakonda, Sivaramakrishna; Kinsey, Sally E.; Sheridan, Eamonn; Thompson, Pamela D.; Irving, Julie A.; Koehler, Rolf; Hoffmann, Per; Nöthen, Markus M.; Heilmann-Heimbach, Stefanie; Jöckel, Karl-Heinz; Easton, Douglas F.; Pharaoh, Paul D. P.; Dunning, Alison M.; Peto, Julian; Canzian, Frederico; Swerdlow, Anthony; Eeles, Rosalind A.; Kote-Jarai, ZSofia; Muir, Kenneth; Pashayan, Nora; Greaves, Mel; Zimmerman, Martin; Bartram, Claus R.; Schrappe, Martin; Stanulla, Martin; Hemminki, Kari; Houlston, Richard S.; Henderson, Brian E.; Haiman, Christopher A.; Benlloch, Sara; Schumacher, Fredrick R.; Olama, Ali Amin Al; Berndt, Sonja I.; Conti, David V.; Wiklund, Fredrik; Chanock, Stephen; Stevens, Victoria L.; Tangen, Catherine M.; Batra, Jyotsna; Clements, Judith; Gronberg, Henrik; Schleutker, Johanna; Albanes, Demetrius; Weinstein, Stephanie; Wolk, Alicja; West, Catharine; Mucci, Lorelei; Cancel-Tassin, Géraldine; Koutros, Stella; Sorensen, Karina Dalsgaard; Maehle, Lovise; Neal, David E.; Travis, Ruth C.; Hamilton, Robert J.; Ingles, Sue Ann; Rosenstein, Barry; Lu, Yong-Jie; Giles, Graham G.; Kibel, Adam S.; Vega, Ana; Kogevinas, Manolis; Penney, Kathryn; Park, Jong Y.; Stanford, Janet L.; Cybulski, Cezary; Nordestgaard, Børge G.; Brenner, Hermann; Maier, Christiane; Kim, Jeri; John, Esther M.; Teixeira, Manuel R.; Neuhausen, Susan L.; De Ruyck, Kim; Razack, Azad; Newcomb, Lisa F.; Lessel, Davor; Kaneva, Radka; Usmani, Nawaid; Claessens, Frank; Townsend, Paul A.; Dominguez, Manuela Gago; Roobol, Monique J.; Menegaux, Florence
    Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10−9, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10−8, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology.
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    Use of 5α-reductase inhibitors for lower urinary tract symptoms and risk of prostate cancer in Swedish men: nationwide, population based case-control study
    (BMJ Publishing Group Ltd., 2013) Robinson, David; Garmo, Hans; Bill-Axelson, Anna; Mucci, Lorelei; Holmberg, Lars; Stattin, Pär
    Objective: To assess the association between 5α-reductase inhibitor (5-ARI) use in men with lower urinary tract symptoms and prostate cancer risk. Design: Nationwide, population based case-control study for men diagnosed with prostate cancer in 2007-09 within the Prostate Cancer data Base Sweden 2.0. Setting: The National Prostate Cancer Register, National Patient Register, census, and Prescribed Drug Register in Sweden, from which we obtained data on 5-ARI use before date of prostate cancer diagnosis. Participants: 26 735 cases and 133 671 matched controls; five controls per case were randomly selected from matched men in the background population. 7815 men (1499 cases and 6316 controls) had been exposed to 5-ARI. 412 men had been exposed to 5-ARI before the diagnosis of a cancer with Gleason score 8-10. Main outcome measures Risk of prostate cancer calculated as odds ratios and 95% confidence intervals by conditional logistic regression analyses. Results: Risk of prostate cancer overall decreased with an increasing duration of exposure; men on 5-ARI treatment for more than three years had an odds ratio of 0.72 (95% confidence interval 0.59 to 0.89; P<0.001 for trend). The same pattern was seen for cancers with Gleason scores 2-6 and score 7 (both P<0.001 for trend). By contrast, the risk of tumours with Gleason scores 8-10 did not decrease with increasing exposure time to 5-ARI (for 0-1 year of exposure, odds ratio 0.96 (95% confidence interval 0.83 to 1.11); for 1-2 years, 1.07 (0.88 to 1.31); for 2-3 years, 0.96 (0.72 to 1.27); for >3 years, 1.23 (0.90 to 1.68); P=0.46 for trend). Conclusions: Men treated with 5-ARI for lower urinary tract symptoms had a decreased risk of cancer with Gleason scores 2-7, and showed no evidence of an increased risk of cancer with Gleason scores 8-10 after up to four years’ treatment.
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    Mediterranean Diet Score and prostate cancer risk in a Swedish population-based case–control study
    (Cambridge University Press, 2013) Möller, Elisabeth; Galeone, Carlotta; Andersson, Therese M.-L.; Bellocco, Rino; Adami, Hans-Olov; Andrén, Ove; Grönberg, Henrik; La Vecchia, Carlo; Mucci, Lorelei; Bälter, Katarina
    Several individual components of the Mediterranean diet have been shown to offer protection against prostate cancer. The present study is the first to investigate the association between adherence to the Mediterranean diet and the relative risk of prostate cancer. We also explored the usefulness of the Mediterranean Diet Score (MDS) in a non-Mediterranean population. FFQ data were obtained from 1482 incident prostate cancer patients and 1108 population-based controls in the Cancer of the Prostate in Sweden (CAPS) study. We defined five MDS variants with different components or using either study-specific intakes or intakes in a Greek reference population as cut-off values between low and high intake of each component. Unconditional logistic regression was used to estimate the relative risk of prostate cancer for high and medium v. low MDS, as well as potential associations with the individual score components. No statistically significant association was found between adherence to the Mediterranean diet based on any of the MDS variants and prostate cancer risk (OR range: 0·96–1·19 for total prostate cancer, comparing high with low adherence). Overall, we found little support for an association between the Mediterranean diet and prostate cancer in this Northern European study population. Despite potential limitations inherent in the study or in the build-up of a dietary score, we suggest that the original MDS with study-specific median intakes as cut-off values between low and high intake is useful in assessing the adherence to the Mediterranean diet in non-Mediterranean populations.
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    Pre-diagnostic circulating sex hormone levels and risk of prostate cancer by ERG tumour protein expression
    (Nature Publishing Group, 2016) Graff, Rebecca; Meisner, Allison; Ahearn, Thomas U; Fiorentino, Michelangelo; Loda, Massimo; Giovannucci, Edward; Mucci, Lorelei; Pettersson, Andreas
    Background: Experimental studies have shown androgen receptor stimulation to facilitate formation of the TMPRSS2:ERG gene fusion in prostate cell lines. No study has tested whether higher pre-diagnostic circulating sex hormone levels in men increase risk of developing TMPRSS2:ERG-positive prostate cancer specifically. Methods: We conducted a nested case–control study of 200 prostate cancer cases and 1057 controls from the Physicians' Health Study and Health Professionals Follow-up Study. We examined associations between pre-diagnostic circulating levels of total testosterone, free testosterone, DHT, androstanediol glucuronide, estradiol, and SHBG and risk of prostate cancer by TMPRSS2:ERG status. TMPRSS2:ERG was estimated by ERG immunohistochemistry. We used multivariable unconditional polytomous logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of ERG-positive (n=94) and, separately, ERG-negative (n=106) disease. Results: Free testosterone was significantly associated with the risk of ERG-positive prostate cancer (OR: 1.37, 95% CI: 1.05–1.77), but not ERG-negative prostate cancer (OR: 1.09, 95% CI: 0.86–1.38) (Pdiff=0.17). None of the remaining hormones evaluated showed clear differential associations with ERG-positive vs ERG-negative disease. Conclusions: These findings provide some suggestive evidence that higher pre-diagnostic free testosterone levels are associated with an increased risk of developing TMPRSS2:ERG-positive prostate cancer.
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    The role of tumor metabolism as a driver of prostate cancer progression and lethal disease: results from a nested case-control study
    (BioMed Central, 2016) Kelly, Rachel; Sinnott, Jennifer; Rider, Jennifer; Noonan, Ericka; Gerke, Travis; Bowden, Michaela; Pettersson, Andreas; Loda, Massimo; Sesso, Howard; Kantoff, Philip; Martin, Neil; Giovannucci, Edward; Tyekucheva, Svitlana; Heiden, Matthew Vander; Mucci, Lorelei
    Background: Understanding the biologic mechanisms underlying the development of lethal prostate cancer is critical for improved therapeutic and prevention strategies. In this study we explored the role of tumor metabolism in prostate cancer progression using mRNA expression profiling of seven metabolic pathways; fatty acid metabolism, glycolysis/gluconeogenesis, oxidative phosphorylation, pentose phosphate, purine metabolism, pyrimidine metabolism and the tricarboxylic acid cycle. Methods: The study included 404 men with archival formalin-fixed, paraffin-embedded prostate tumor tissue from the prospective Health Professionals Follow-up Study and Physicians’ Health Study. Lethal cases (n = 113) were men who experienced a distant metastatic event or died of prostate cancer during follow-up. Non-lethal controls (n = 291) survived at least 8 years post-diagnosis without metastases. Of 404 men, 202 additionally had matched normal tissue (140 non-lethal, 62 lethal). Analyses compared expression levels between tumor and normal tissue, by Gleason grade and by lethal status. Secondary analyses considered the association with biomarkers of cell proliferation, apoptosis and angiogenesis. Results: Oxidative phosphorylation and pyrimidine metabolism were identified as the most dysregulated pathways in lethal tumors (p < 0.007), and within these pathways, a number of novel differentially expressed genes were identified including POLR2K and APT6V1A. The associations were tumor specific as there was no evidence any pathways were altered in the normal tissue of lethal compared to non-lethal cases. Conclusions: The results suggest prostate cancer progression and lethal disease are associated with alterations in key metabolic signaling pathways. Pathways supporting proliferation appeared to be of particular importance in prostate tumor aggressiveness. Electronic supplementary material The online version of this article (doi:10.1186/s40170-016-0161-9) contains supplementary material, which is available to authorized users.
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    CanWalk: study protocol for a randomized feasibility trial of a walking intervention for people with recurrent or metastatic cancer
    (BioMed Central, 2015) Harris, Jenny; Tsianakas, Vicki; Ream, Emma; Van Hemelrijck, Mieke; Purushotham, Arnie; Mucci, Lorelei; Green, James SA; Robb, Karen; Fewster, Jacquetta; Armes, Jo
    Background: Increasing numbers of people in the UK are living with recurrent or metastatic cancer, many of whom experience reduced quality of life resulting from the physical and psychosocial consequences of cancer and its treatment. While drug treatments are important at alleviating some symptoms, there is increasing evidence of the benefits of exercise in enhancing quality of life and health outcomes. Walking is an inexpensive and accessible form of exercise. To our knowledge, no studies have investigated whether a walking intervention is sufficient to enhance quality of life and alleviate symptoms in people with recurrent or metastatic cancer across a range of tumor types. This paper describes the CanWalk study protocol, which aims to assess the feasibility and acceptability of undertaking a randomized controlled trial of a community-based walking program to enhance quality of life and well-being in people with recurrent or metastatic cancer. Methods: A mixed methods feasibility study includes an exploratory two-center randomized controlled trial and qualitative interviews. A minimum of 60 participants will be recruited from two London NHS Trusts and randomized 1:1 between the walking intervention and standard care using minimization. The walking intervention consists of the initial provision of written/online information followed by a short motivational interview. Participants are instructed to walk for 30 min on alternate days and attend an organized volunteer-led walk once a week. Half of all participants will be asked to use a pedometer. Postal questionnaires will be completed at baseline (pre-randomization) and at 6, 12 and 24 weeks. A subsample of participants and stakeholders will be interviewed at the end of the study. Results: Primary outcomes will be the acceptability and feasibility of the intervention and trial. A range of secondary outcome assessments needed to design a main study, including estimates of recruitment, adherence and variability in quality of life, will be evaluated. Conclusions: Data from this study will be used to refine the walking intervention, investigate the acceptability of the intervention and study design, and determine the most appropriate outcome measures thereby providing estimates of the factors needed to design the main study. Trial registration ISRCTN42072606.