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The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population‐based to a more “personalized” approach to cancer staging
Amin, Mahul B. , Greene, Frederick L. , Edge, Stephen B. , Compton, Carolyn C. , Gershenwald, Jeffrey E., Brookland, Robert K., Meyer, Laura, Gress, Donna M., Byrd, David R. , Winchester, David P., Gershenwald, Jeffrey E.

CA: A Cancer Journal for Clinicians | January 17, 2017 | Volume: 67 | Issue: 2 | Pages: 93-99

10.3322/caac.21388 | PMID 28094848 Get It

Abstract The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM‐based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual , the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a “population‐based” to a more “personalized” approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge‐based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as “what's new” in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93–99. © 2017 American Cancer Society.
International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease
Fajgenbaum, David C. , Bagg, Adam , Frank, Dale , Wu, David , Srkalović, Gordan , Simpson, David , Liu, Amy , Menke, David M. , Lechowicz, Mary Jo , Wong, Raymond , Pierson, Sheila K. , Paessler, Michele, Rossi, Jean‐François, Ide, Makoto , Ruth, Jason R., Croglio, M.P. , Suarez, Alexander , Chadburn, Amy , Colleoni, Gisele W. B. , Jayanthan, Raj , Nabel, Christopher S. , Kelleher, Dermot, Voorhees, Peter M. , Yoshizaki, Kazuyuki , Oksenhendler, Éric , Elenitoba‐Johnson, Kojo S.J. , Lim, Megan S. , Menke, David, Wong, Raymond S M , Uldrick, Thomas S. , Chandrakasan, Shanmuganathan , Rossi, Jean‐François , Krymskaya, Vera P. , Nasta, Sunita , Casper, Corey , Dispenzieri, Angela , Fosså, Alexander , Kurzrock, Razelle , Doǧan, Ahmet , Rhee, Frits van , Jaffe, Elaine S. , Fajgenbaum, David C , Ide, Makoto , Lim, Megan S

Blood | January 13, 2017 | Volume: 129 | Issue: 12 | Pages: 1646-1657

10.1182/blood-2016-10-746933 | PMID 28087540 Get It

Key Points An international panel established the first ever diagnostic criteria for iMCD based on review of 244 clinical cases and 88 tissue samples. The criteria require multicentric lymphadenopathy with defined histopathology, ≥2 clinical/laboratory changes, and exclusion of iMCD mimics.
Mental health issues in survivors of sex trafficking
Levine, James A.

Cogent Medicine | January 6, 2017 | Volume: 4 | Issue: 1 | Pages: 1278841

10.1080/2331205x.2017.1278841 Get It

Outcomes of definitive chemoradiation in patients with esophageal cancer
Mikhail, Sameh , Wei, Lai , Salem, Mohamed E. , Bekaii‐Saab, Tanios , Wei, Lai , Bekaii-Saab, Tanios S

Diseases of the Esophagus | November 21, 2016 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1111/dote.12506 | PMID 27868290 Get It

External Mechanical Devices and Vascular Surgery for Erectile Dysfunction
Trost, Landon , Munarriz, Ricardo , Wang, Run , Morey, Allen F. , Levine, Laurence A. , Trost, Landon W

The Journal of Sexual Medicine | October 20, 2016 | Volume: 13 | Issue: 11 | Pages: 1579-1617

10.1016/j.jsxm.2016.09.008 | PMID 27770853 Get It

ABSTRACTIntroductionThe field of sexual medicine is continuously advancing, with novel outcomes reported on a regular basis. Given the rapid evolution, updated guidelines are essential to inform practicing clinicians on best practices.AimTo summarize the current literature and provide clinical guidelines on penile traction therapy, vacuum erection devices, and penile revascularization.MethodsA consensus panel was held with leading sexual medicine experts during the 2015 International Consultation on Sexual Medicine (ICSM). Relevant literature was reviewed and graded based on Oxford criteria to develop evidence-based guideline and consensus statements.Main Outcome MeasuresThe development of clinically relevant guidelines.ResultsPenile traction therapy is a viable therapy to modestly improve penile length as a primary therapy, before penile prosthesis placement in men with decreased penile length or after surgery for Peyronie's disease. It also might have a role in the acute phase of Peyronie's disease but has inconsistent outcomes in the long-term phase. Vacuum erection devices are effective in creating an erection satisfactory for intercourse, even in difficult-to-treat populations. They also might be used in the post-prostatectomy setting to maintain penile length but have insufficient evidence as a penile rehabilitation therapy. For vasculogenic erectile dysfunction, men with suspected arterial insufficiency can be evaluated with penile Duplex Doppler ultrasonography and confirmatory angiography. Penile revascularization procedures have consistently demonstrated benefits in very select patient populations; however, inadequate data exists to suggest the superiority of one technique. Men with vascular risk factors are likely poor candidates for penile revascularization, although veno-occlusive dysfunction and age are less significant. Therapies for treating primary veno-occlusive dysfunction are not recommended and should be reserved for clinical trials.ConclusionsSince the prior ICSM meeting, multiple developments have occurred in external mechanical devices and penile revascularization for the treatment of erectile and sexual dysfunction. Sexual medicine clinicians are encouraged to review and incorporate recommendations as applicable to their scope of practice.
No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival
Sucheston‐Campbell, Lara, Cannioto, Rikki , Clay‐Gilmour, Alyssa , Etter, John Lewis , Eng, Kevin H., Liu, Song , Battaglia, Sebastiano , Szender, J. Brian, Minlikeeva, Albina N. , Joseph, Janine M. , Mayor, Paul , Abrams, Scott I. , Wallace, Paul K. , Soh, Kah Teong , Zsíros, Emese , Beckmann, Matthias W. , Bruegl, Amanda , Campbell, Ian , Campbell, Shawn, Chenevix‐Trench, Georgia , Diergaarde, Brenda , Doerk, Thilo, Eccles, Diana , Engelholm, Svend Aage, Fasching, Peter A. , Gayther, Simon A. , Goodman, Marc T. , Harter, Philipp , Hein, Alexander , Heitz, Florian , Hillemmanns, Peter, Høgdall, Claus , Høgdall, Estrid , Huzarski, Tomasz , Jensen, Allan , Johnatty, Sharon E. , Jung, Audrey , Klapdor, Reudiger, Kluz, Tomasz , Konopka, Bożena , Kupryjańczyk, Jolanta , Lambrechts, Diether , Lester, Jenny, Lubiński, Jan , Levine, Douglas A. , Lundvall, Lene, McGuire, Valerie , McNeish, Iain A. , Menon, Usha , Ness, Roberta B., Oršulić, Sandra , Pearce, Celeste Leigh, Ramus, Susan J. , Rothstein, Joseph H. , Rossing, Mary Anne, Rübner, Matthias, Schildkraut, Joellen M. , Schmalfeldt, Barbara , Schwaab, Ira, Sieh, Weiva , Sobiczewski, Piotr , Song, Honglin , Terry, Kathryn L. , Nieuwenhuysen, Els Van , Vanderstichele, Adriaan , Vergote, Ignace , Walsh, Christine , Webb, Penelope M. , Wentzensen, Nicolas , Whittemore, Alice S. , Wu, Anna H. , Odunsi, Kunle , Chang‐Claude, Jenny , Goode, Ellen L. , Moysich, Kirsten B. , Dörk, Thilo , Bowtell, David D.L. , Lambrechts, Diether , Clay, Alyssa I, Hu, Qiang , Segal, Brahm H. , Anton‐Culver, Hoda , Bandera, Elisa V. , Berchuck, Andrew , Bjørge, Line , Cramer, Daniel W. , Dansonka‐Mieszkowska, Agnieszka , Dao, Fanny , Doherty, Jennifer A. , Bois, Andreas du , Gentry‐Maharaj, Aleksandra , Glasspool, Rosalind , Gronwald, Jacek , Karlan, Beth Y. , Kjær, Susanne K. , Modugno, Francesmary , Paul, James , Pejovic, Tanja B. , Pharoah, Paul D.P. , Siddiqui, Nadeem , Ziogas, Argyrios , Dörk, Thilo , Lambrechts, Diether , McNeish, Iain A , Ramus, Susan J , Vanderstichele, Adriaan , Webb, Penelope M , Hein, Alexander , Jensen, Allan , Eccles, Diana , Menon, Usha , Moysich, Kirsten , Campbell, Ian G , Heitz, Florian , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Huzarski, Tomasz , Jung, Audrey Y , Bowtell, David D , Diergaarde, Brenda , Lubinski, Jan , Kluz, Tomasz , Goodman, Marc T

Cancer Epidemiology, Biomarkers & Prevention | September 28, 2016 | Volume: 26 | Issue: 3 | Pages: 420-424

10.1158/1055-9965.epi-16-0631 | PMID 27677730 Get It

Abstract Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P < 3.5 × 10−5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420–4. ©2016 AACR.
Addressing obesity in homeless children
Levine, James A. , McCrady-Spitzer, Shelly , Batko, S. M., McCrady-Spitzer, Shelly K, Batko, Samantha

Science | September 22, 2016 | Volume: 353 | Issue: 6306 | Pages: 1374-1375

10.1126/science.aaj1468 | PMID 27708029 Get It

Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors
Holtan, Shernan G. , Khera, Nandita , Levine, John E. , Chai, Xiaoyu , Storer, Barry E. , Liu, Hien , Inamoto, Yoshihiro , Mayer, Sebastian , Arora, Mukta , Palmer, Jeanne , Lukez, Alexander , Arai, Sally , Lazaryan, Aleksandr , Newell, Laura F. , Krupski, Christa , Jagasia, Madan , Pusic, Iskra , Wood, William A. , Renteria, Anne S. , Yanik, Gregory A. , Ayuk, Francis , Holler, Ernst , Watanaboonyongcharoen, Phandee , Efebera, Yvonne A. , Ferrara, James L.M. , Weisdorf, Daniel J. , Lee, Stephanie J. , Pidala, Joseph, Chen, George L. , Flowers, Mary E.D. , Cutler, Corey S. , Hogan, William J. , Hexner, Elizabeth O. , Panoskaltsis‐Mortari, Angela , Weisdorf, Dan , Levine, John E , Holtan, Shernan , Lee, Stephanie J , Wood, William A

Blood | September 14, 2016 | Volume: 128 | Issue: 19 | Pages: 2350-2358

10.1182/blood-2015-09-669846 | PMID 27625357 Get It

Key Points Under current treatment approaches, patients with LA GVHD have poor overall and failure-free survival. Levels of AREG are elevated in LA GVHD, and the AREG/EGF ratio is predictive of overall survival and nonrelapse mortality in LA GVHD.
PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS
Southey, Melissa C. , Goldgar, David E, Winqvist, Robert , Pylkäs, Katri , Michailidou, Kyriaki , Rensburg, Elizabeth J. van , Heikkinen, Tuomas , Hopper, John L. , Dörk, Thilo , Claes, Kathleen , Teo, Zhi L. , Radice, Paolo , Catucci, Irene, Peterlongo, Paolo , Odefrey, Fabrice, Dowty, James G., Schmidt, Marjanka K. , Hogervorst, Frans B.L., Verhoef, Senno, Carpenter, Jane, Clarke, Christine L. , Scott, Rodney J. , Fasching, Peter A. , Haeberle, Lothar, Ekici, Arif B. , Beckmann, Matthias W. , Peto, Julian , Fletcher, Olivia , Johnson, Nichola , Bolla, Manjeet K. , Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Miller, Nicola, Marmé, F., Burwinkel, Barbara , Guénel, Pascal , Truong, Thérèse , Sanchez, Marie, Bojesen, Stig E. , Nielsen, Sune F. , Flyger, Henrik, Benı́tez, Javier , Zamora, M. Pilar , Menéndez, Primitiva, Brenner, Hermann , Stegmaier, Christa, Brauch, Hiltrud , Brüning, Thomas , Ko, Yon‐Dschun, Muranen, Taru , Aittomäki, Kristiina, Blomqvist, Carl , Bogdanova, Natalia , Antonenkova, Natalia, Lindblom, Annika , Margolin, Sara , Mannermaa, Arto, Kataja, Vesa , Kosma, Veli‐Matti , Hartikainen, Jaana M. , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Wauters, Els , Smeets, Dominiek, Beuselinck, Benoit , Floris, Giuseppe , Chang‐Claude, Jenny , Flesch‐Janys, Dieter, Vachon, Celine M. , McLean, Catriona , Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick R. , Kristensen, Vessela, Alnæs, Grethe Grenaker, Zheng, Wei , Hunter, David J. , Lindström, Sara, Hankinson, Susan E. , Kraft, Peter , Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Jukkola‐Vuorinen, Arja , Grip, Mervi, Kauppila, Saila , Devilee, Peter , Tollenaar, Robert A.E.M., Seynaeve, Caroline, García‐Closas, Montserrat , Figueroa, Jonine D. , Lissowska, Jolanta , Darabi, Hatef, Eriksson, Mikael , Eccles, Diana M, Tapper, William , Gerty, Sue, Hooning, Maartje J. , Collée, J. Margriet, Tilanus‐Linthorst, Madeleine M.A., Li, Jingmei , Brand, Judith S. , Humphreys, Keith , Reed, Malcolm , Luccarini, Craig , Baynes, Caroline, Dunning, Alison M. , Hamann, Ute, Torres, Diana , Ulmer, Hans Ulrich, Rüdiger, Thomas , Jakubowska, Anna , Lubiński, Jan , Jaworska, Katarzyna, Durda, Katarzyna, Slager, Susan, Yannoukakos, Drakoulis , Swerdlow, Anthony J. , Ashworth, Alan , Orr, Nick , Jones, Michael E. , González‐Neira, Anna , Pita, Guillermo , Alonso, M. Rosario, Álvarez, Núria, Herrero, Daniel, Tessier, Daniel C., Vincent, Daniel , Bacot, François, Simard, Jacques , Dumont, Martine , Soucy, Penny, Eeles, Rosalind A. , Muir, Kenneth , Grönberg, Henrik , Schleutker, Johanna , Nordestgaard, Børge G. , Weischer, Maren , Travis, Ruth C. , Neal, David E. , Donovan, Jenny , Hamdy, Freddie C. , Stanford, Janet L. , Blot, William J. , Thibodeau, Stephen N. , Schaid, Daniel J. , Kelley, Joseph L., Maier, Christiane, Kibel, Adam S. , Butterbach, Katja, Kaneva, Radka , Batra, Jyotsna , Teixeira, Manuel R. , Olama, Ali Amin Al , Benlloch, Sara, Hartmann, Arndt , Hein, Alexander , Ruebner, Matthias , Lambrechts, Diether , Nieuwenhuysen, Els Van , Vergote, Ignace , Lambretchs, Sandrina, Rossing, Mary Anne, Nickels, Stefan , Eilber, Ursula, Wang‐Gohrke, Shan , Odunsi, Kunle , Sucheston‐Campbell, Lara, Friel, Grace , Lurie, Galina, Killeen, Jeffrey , Goodman, Marc T. , Runnebaum, Ingo B., Hillemanns, Peter , Pelttari, Liisa M. , Edwards, Robert P., Ness, Roberta B., Moysich, Kirsten B., Heitz, Florian , Harter, Philipp , Kommoss, Stefan , Walsh, Christine , Lester, Jenny, Jensen, Allan , Høgdall, Estrid , Peissel, Bernard , Bernard, Loris, Goode, Ellen L. , Vierkant, Robert A. , Cunningham, Julie M. , Fogarty, Zachary C. , Kalli, Kimberly R., Liang, Dong , Lu, Karen H., Hildebrandt, Michelle A.T., Wu, Xifeng , Levine, Douglas A. , Bisogna, Maria, Iversen, Edwin S., Marks, Jeffrey R. , Akushevich, Lucy , Schildkraut, Joellen M. , Terry, Kathryn L. , Stampfer, Meir J. , Tworoger, Shelley S. , Olson, Sara H. , Salvesen, Helga B., Altena, Anne M. van , Aben, Katja K.H. , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Bean, Yukie T., Kelemen, Linda E., Le, Nhu D. , Górski, Bohdan , Menkiszak, Janusz , Høgdall, Claus , Lundvall, Lene, Nedergaard, Lotte , Engelholm, Svend Aage, Dicks, Ed , Campbell, Ian , McNeish, Iain A. , Whittemore, Alice S. , Rothstein, Joseph H. , McGuire, Valerie, Sieh, Weiva , Cai, Hui , Teten, Rachel Threet, Sutphen, Rebecca , McLaughlin, John R, Narod, Steven A., Phelan, Catherine M., Monteiro, Álvaro N.A. , Fenstermacher, David, Lin, Hui‐Yi , Sellers, Thomas A. , Chen, Y. Ann , Chen, Zhihua , Gayther, Simon A. , Ramus, Susan J. , Menon, Usha , Wu, Anna H. , Pearce, Celeste Leigh, Pike, Malcolm C., Dansonka‐Mieszkowska, Agnieszka , Plisiecka-Hałasa, Joanna, Moes-Sosnowska, Joanna , Kupryjańczyk, Jolanta , Song, Honglin , Winship, Ingrid , Chenevix‐Trench, Georgia , Tavtigian, Sean V. , Easton, Doug , Lu, Karen H. , Durocher, Francine , Eccles, Diana , Lambrechts, Diether , Vachon, Celine, Pankratz, Vernon S, Thibodeau, Stephen, Goldgar, David E, Couch, Fergus J. , Tischkowitz, Marc D. , Foulkes, William D. , Dennis, Joe , Nevanlinna, Heli , Reis‐Filho, Jorge S. , Tsimiklis, Helen , Broeks, Annegien , dos‐Santos‐Silva, Isabel , Yang, Rongxi , Ménégaux, F. , Sanchez, Marie, Pérez, José Ignacio Arias , Anton‐Culver, Hoda , Neuhausen, Susan L. , Ziogas, Argyrios , Clarke, Christina A. , Arndt, Volker , Mannermaa, Arto, Spurdle, Amanda B. , Group, Australian Ovarian Cancer Study, Rudolph, Anja , Seibold, Petra , Olson, Janet E. , Vachon, Celine M. , Pankratz, V. Shane , Marchand, Loı̈c Le , Kristensen, Vessela N. , Hankinson, Susan E. , Hollestelle, Antoinette , Chanock, Stephen Jacob , Czene, Kamila , Eriksson, Mikael , Eccles, Diana M, Rafiq, Sajjad , Hooning, Maartje J. , Martens, John W.M. , Hall, Per N , Cox, Angela , Toland, Amanda Ewart , Ambrosone, Christine B. , Wiklund, Fredrik E. , Khaw, Kay‐Tee , Cybulski, Cezary , Cannon‐Albright, Lisa , Park, Jong, Kote‐Jarai, Zsofia , Renner, Stefan P. , Doherty, Jennifer A. , Wilkens, Lynne R. , Bützow, Ralf C. , Modugno, Francesmary , Moysich, Kirsten B., Bois, Andreas du , Karlan, Beth Y. , Kjær, Susanne K. , Bonanni, Bernardo , Fridley, Brooke L. , Larson, Melissa C. , Hildebrandt, Michelle A.T. , Dao, Fanny , Berchuck, Andrew , Cramer, Daniel W. , Poole, Elizabeth M. , Bandera, Elisa V. , Orlow, Irene , Bjørge, Line , Pejovic, Tanja B. , Brooks‐Wilson, Angela , Cook, Linda S. , Gronwald, Jacek , Tyrer, Jonathan P. , Paul, James , Siddiqui, Nadeem , Glasspool, Rosalind , Shu, Xiao‐Ou , McLaughlin, John R, Permuth, Jennifer B. , Gentry‐Maharaj, Aleksandra , Berg, David Van Den , Pharoah, Paul D.P. , Giles, Graham G. , Milne, Roger L. , Pelttari, L M , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Tworoger, Shelley S , van Rensburg, Elizabeth J , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Monteiro, Alvaro N , Swerdlow, Anthony J , Moysich, Kirsten , Radice, Paolo , Lissowska, Jolanta , Claes, Kathleen B M , Campbell, Ian G , Eeles, Rosalind A , Southey, Melissa C , Menkiszak, Janusz , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Lin, Hui-Yi , Fogarty, Zachary C , Dunning, Alison M , Heitz, Florian , Jakubowska, Anna , Jones, Michael E , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Brenner, Hermann , Guénel, Pascal , Li, Jingmei , Muranen, Taru A , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Winship, Ingrid M , Ekici, Arif B , Michailidou, Kyriaki , Hartikainen, Jaana M , Bogdanova, Natalia V , Kraft, Peter , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Høgdall, Estrid , Høgdall, Claus K , Batra, Jyotsna , Pylkäs, Katri , Yannoukakos, Drakoulis , Devilee, Peter , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Goodman, Marc T , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick

Journal of Medical Genetics | September 5, 2016 | Volume: 53 | Issue: 12 | Pages: 800-811

10.1136/jmedgenet-2016-103839 | PMID 27595995 Get It

Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
Chair-based fidgeting and energy expenditure
Koepp, Gabriel A., Moore, Graham K, Levine, James A.

BMJ Open Sport & Exercise Medicine | September 1, 2016 | Volume: 2 | Issue: 1 | Pages: e000152

10.1136/bmjsem-2016-000152 | PMID 27900194 Get It

Introduction Sedentariness is associated with chronic health conditions, impaired cognitive function and obesity. Work contributes significantly to sedentariness because many work tasks necessitate sitting. Few sustained solutions exist to reverse workplace sedentariness. Here, we evaluated a chair and an under-table device that were designed to promote fidgeting while seated. Our hypothesis was that an under-table leg-fidget bar and/or a fidget-promoting chair significantly increased energy expenditure. We compared these devices with chair-based exercise and walking. Materials and methods We measured energy expenditure and heart rate in 16 people while they sat and worked using a standard chair, an under-desk device that encourages leg fidgeting and a fidget-promoting chair. We compared outcomes with chair-based exercise and walking. Results Energy expenditure increased significantly while using either an under-table leg-fidget bar or a fidget-promoting chair, when compared to the standard office chair (standard chair, 76±31 kcal/hour; leg-fidget bar, 98±42 kcal/hour (p<0.001); fidget chair, 89±40 kcal/hour (p=0.03)). However, heart rate did not increase significantly in either case. Bouts of exercise performed while seated provided energetic and heart rate equivalency to walking at 2 mph. Conclusions Chairs and devices that promote fidgeting can increase energy expenditure by ∼20–30% but not increase heart rate. Dynamic sitting may be among a lexicon of options to help people move more while at work.