Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151290/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151290/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaye, Jane -- Meslin, Eric M -- Knoppers, Bartha M -- Juengst, Eric T -- Deschenes, Mylene -- Cambon-Thomsen, Anne -- Chalmers, Donald -- De Vries, Jantina -- Edwards, Kelly -- Hoppe, Nils -- Kent, Alastair -- Adebamowo, Clement -- Marshall, Patricia -- Kato, Kazuto -- 096599/2/11/Z/Wellcome Trust/United Kingdom -- 097671/Z/11/Z/Wellcome Trust/United Kingdom -- P50 HG003390/HG/NHGRI NIH HHS/ -- P50 HG3374/HG/NHGRI NIH HHS/ -- P50-HG-03390-07/HG/NHGRI NIH HHS/ -- R25 TW007091/TW/FIC NIH HHS/ -- R25TW007091/TW/FIC NIH HHS/ -- UL1RR025761-01/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2012 May 11;336(6082):673-4. doi: 10.1126/science.1218015.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉HeLEX, Department of Public Health, University of Oxford, OX3 7LF, Oxford, UK. jane.kaye@law.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22582247" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138491/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138491/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉H3Africa Consortium -- Rotimi, Charles -- Abayomi, Akin -- Abimiku, Alash'le -- Adabayeri, Victoria May -- Adebamowo, Clement -- Adebiyi, Ezekiel -- Ademola, Adebowale D -- Adeyemo, Adebowale -- Adu, Dwomoa -- Affolabi, Dissou -- Agongo, Godfred -- Ajayi, Samuel -- Akarolo-Anthony, Sally -- Akinyemi, Rufus -- Akpalu, Albert -- Alberts, Marianne -- Alonso Betancourt, Orlando -- Alzohairy, Ahmed Mansour -- Ameni, Gobena -- Amodu, Olukemi -- Anabwani, Gabriel -- Andersen, Kristian -- Arogundade, Fatiu -- Arulogun, Oyedunni -- Asogun, Danny -- Bakare, Rasheed -- Balde, Naby -- Baniecki, Mary Lynn -- Beiswanger, Christine -- Benkahla, Alia -- Bethke, Lara -- Boehnke, Micheal -- Boima, Vincent -- Brandful, James -- Brooks, Andrew I -- Brosius, Frank C -- Brown, Chester -- Bucheton, Bruno -- Burke, David T -- Burnett, Barrington G -- Carrington-Lawrence, Stacy -- Carstens, Nadia -- Chisi, John -- Christoffels, Alan -- Cooper, Richard -- Cordell, Heather -- Crowther, Nigel -- Croxton, Talishiea -- de Vries, Jantina -- Derr, Leslie -- Donkor, Peter -- Doumbia, Seydou -- Duncanson, Audrey -- Ekem, Ivy -- El Sayed, Ahmed -- Engel, Mark E -- Enyaru, John C K -- Everett, Dean -- Fadlelmola, Faisal M -- Fakunle, Eyitayo -- Fischbeck, Kenneth H -- Fischer, Anne -- Folarin, Onikepe -- Gamieldien, Junaid -- Garry, Robert F -- Gaseitsiwe, Simani -- Gbadegesin, Rasheed -- Ghansah, Anita -- Giovanni, Maria -- Goesbeck, Parham -- Gomez-Olive, F Xavier -- Grant, Donald S -- Grewal, Ravnit -- Guyer, Mark -- Hanchard, Neil A -- Happi, Christian T -- Hazelhurst, Scott -- Hennig, Branwen J -- Hertz-, Christiane -- Fowler -- Hide, Winston -- Hilderbrandt, Friedhelm -- Hugo-Hamman, Christopher -- Ibrahim, Muntaser E -- James, Regina -- Jaufeerally-Fakim, Yasmina -- Jenkins, Carolyn -- Jentsch, Ute -- Jiang, Pan-Pan -- Joloba, Moses -- Jongeneel, Victor -- Joubert, Fourie -- Kader, Mukthar -- Kahn, Kathleen -- Kaleebu, Pontiano -- Kapiga, Saidi H -- Kassim, Samar Kamal -- Kasvosve, Ishmael -- Kayondo, Jonathan -- Keavney, Bernard -- Kekitiinwa, Adeodata -- Khan, Sheik Humarr -- Kimmel, Paul -- King, Mary-Claire -- Kleta, Robert -- Koffi, Mathurin -- Kopp, Jeffrey -- Kretzler, Matthias -- Kumuthini, Judit -- Kyobe, Samuel -- Kyobutungi, Catherine -- Lackland, Daniel T -- Lacourciere, Karen A -- Landoure, Guida -- Lawlor, Rita -- Lehner, Thomas -- Lesosky, Maia -- Levitt, Naomi -- Littler, Katherine -- Lombard, Zane -- Loring, Jeanne F -- Lyantagaye, Sylvester -- Macleod, Annette -- Madden, Ebony B -- Mahomva, Chengetai R -- Makani, Julie -- Mamven, Manmak -- Marape, Marape -- Mardon, Graeme -- Marshall, Patricia -- Martin, Darren P -- Masiga, Daniel -- Mason, Robin -- Mate-Kole, Michael -- Matovu, Enock -- Mayige, Mary -- Mayosi, Bongani M -- Mbanya, Jean Claude -- McCurdy, Sheryl A -- McCarthy, Mark I -- McIlleron, Helen -- Mc'Ligeyo, S O -- Merle, Corrine -- Mocumbi, Ana Olga -- Mondo, Charles -- Moran, John V -- Motala, Ayesha -- Moxey-Mims, Marva -- Mpoloka, Wata Sununguko -- Msefula, Chisomo L -- Mthiyane, Thuli -- Mulder, Nicola -- Mulugeta, Gebregziab her -- Mumba, Dieuodonne -- Musuku, John -- Nagdee, Mo -- Nash, Oyekanmi -- Ndiaye, Daouda -- Nguyen, Anh Quynh -- Nicol, Mark -- Nkomazana, Oathokwa -- Norris, Shane -- Nsangi, Betty -- Nyarko, Alexander -- Nyirenda, Moffat -- Obe, Eileen -- Obiakor, Reginald -- Oduro, Abraham -- Ofori-Acquah, Solomon F -- Ogah, Okechukwu -- Ogendo, Stephen -- Ohene-Frempong, Kwaku -- Ojo, Akinlolu -- Olanrewaju, Timothy -- Oli, John -- Osafo, Charlotte -- Ouwe Missi Oukem-Boyer, Odile -- Ovbiagele, Bruce -- Owen, Andrew -- Owolabi, Mayowa Ojo -- Owolabi, Lukman -- Owusu-Dabo, Ellis -- Pare, Guillaume -- Parekh, Rulan -- Patterton, Hugh G -- Penno, Margaret B -- Peterson, Jane -- Pieper, Rembert -- Plange-Rhule, Jacob -- Pollak, Martin -- Puzak, Julia -- Ramesar, Rajkumar S -- Ramsay, Michele -- Rasooly, Rebekah -- Reddy, Shiksha -- Sabeti, Pardis C -- Sagoe, Kwamena -- Salako, Tunde -- Samassekou, Oumar -- Sandhu, Manjinder S -- Sankoh, Osman -- Sarfo, Fred Stephen -- Sarr, Marie -- Shaboodien, Gasnat -- Sidibe, Issa -- Simo, Gustave -- Simuunza, Martin -- Smeeth, Liam -- Sobngwi, Eugene -- Soodyall, Himla -- Sorgho, Hermann -- Sow Bah, Oumou -- Srinivasan, Sudha -- Stein, Dan J -- Susser, Ezra S -- Swanepoel, Carmen -- Tangwa, Godfred -- Tareila, Andrew -- Tastan Bishop, Ozlem -- Tayo, Bamidele -- Tiffin, Nicki -- Tinto, Halidou -- Tobin, Ekaete -- Tollman, Stephen Meir -- Traore, Mahamadou -- Treadwell, Marsha J -- Troyer, Jennifer -- Tsimako-Johnstone, Masego -- Tukei, Vincent -- Ulasi, Ifeoma -- Ulenga, Nzovu -- van Rooyen, Beverley -- Wachinou, Ablo Prudence -- Waddy, Salina P -- Wade, Alisha -- Wayengera, Misaki -- Whitworth, James -- Wideroff, Louise -- Winkler, Cheryl A -- Winnicki, Sarah -- Wonkam, Ambroise -- Yewondwos, Mengistu -- sen, Tadase -- Yozwiak, Nathan -- Zar, Heather -- 085349/Wellcome Trust/United Kingdom -- 095009/Wellcome Trust/United Kingdom -- 095201/Wellcome Trust/United Kingdom -- 098504/Wellcome Trust/United Kingdom -- 104111/Wellcome Trust/United Kingdom -- MC_U123292700/Medical Research Council/United Kingdom -- P20 MD006899/MD/NIMHD NIH HHS/ -- R01 AI104621/AI/NIAID NIH HHS/ -- RG/08/012/25941/British Heart Foundation/United Kingdom -- U01 HG007044/HG/NHGRI NIH HHS/ -- U41 HG006941/HG/NHGRI NIH HHS/ -- U54 AI110398/AI/NIAID NIH HHS/ -- U54 HG006938/HG/NHGRI NIH HHS/ -- U54 HG006939/HG/NHGRI NIH HHS/ -- U54 HG007479/HG/NHGRI NIH HHS/ -- UH2 HG007051/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 20;344(6190):1346-8. doi: 10.1126/science.1251546.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24948725" target="_blank"〉PubMed〈/a〉

Description: Multiple breast cancer susceptibility loci have been identified in genome-wide association studies (GWAS) in populations of European and Asian ancestry using array chips optimized for populations of European ancestry. It is important to examine whether these loci are associated with breast cancer risk in women of African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19 loci in a pooled case–control study of breast cancer, which included 1509 cases and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the USA; all women were of African ancestry. We found significant associations for three SNPs, which were in the same direction and of similar magnitude as those reported in previous fine-mapping studies in women of African ancestry. The allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04–1.47; P = 0.018] for the rs2981578-G allele (10q26/ FGFR2 ), 1.34 (95% CI: 1.10–1.63; P = 0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00–1.25; P = 0.04) for the rs3104793-C allele (16q12). Although a significant association was observed for an additional index SNP (rs3817198), it was in the opposite direction to prior GWAS studies. In conclusion, this study highlights the complexity of applying current GWAS findings across racial/ethnic groups, as none of GWAS-identified index SNPs could be replicated in women of African ancestry. Further fine-mapping studies in women of African ancestry will be needed to reveal additional and causal variants for breast cancer.

Description: Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P 〈 0.05. Through fine-mapping, in three regions ( 1q32 , 3p24, 10q25 ), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P 〈 5 x 10 –6 ) in three separate regions ( 6q25, 14q13 , 22q12 ) that may represent novel risk variants. Directional consistency of association observed for ~65–70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry.

Description: Purpose: Detecting signals of micrometastatic disease in patients with early breast cancer (EBC) could improve risk stratification and allow better tailoring of adjuvant therapies. We previously showed that postoperative serum metabolomic profiles were predictive of relapse in a single-center cohort of estrogen receptor (ER)–negative EBC patients. Here, we investigated this further using preoperative serum samples from ER-positive, premenopausal women with EBC who were enrolled in an international phase III trial. Experimental Design: Proton nuclear magnetic resonance (NMR) spectroscopy of 590 EBC samples (319 with relapse or ≥6 years clinical follow-up) and 109 metastatic breast cancer (MBC) samples was performed. A Random Forest (RF) classification model was built using a training set of 85 EBC and all MBC samples. The model was then applied to a test set of 234 EBC samples, and a risk of recurrence score was generated on the basis of the likelihood of the sample being misclassified as metastatic. Results: In the training set, the RF model separated EBC from MBC with a discrimination accuracy of 84.9%. In the test set, the RF recurrence risk score correlated with relapse, with an AUC of 0.747 in ROC analysis. Accuracy was maximized at 71.3% (sensitivity, 70.8%; specificity, 71.4%). The model performed independently of age, tumor size, grade, HER2 status and nodal status, and also of Adjuvant! Online risk of relapse score. Conclusions: In a multicenter group of EBC patients, we developed a model based on preoperative serum metabolomic profiles that was prognostic for disease recurrence, independent of traditional clinicopathologic risk factors. Clin Cancer Res; 23(6); 1422–31. ©2017 AACR .

Description: Background Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. Methods We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. Results Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, –0.59; 95% CI, –0.86 to –0.31), BMI (SMD, –0.32; 95% CI, –0.45 to –0.18), SBP (SMD, –0.40; 95% CI, –0.55 to –0.25) and DBP (SMD, –0.34; 95% CI, –0.51 to –0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, –0.34; 95% CI, –0.62 to –0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. Conclusions Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.

Description: Objectives To explore the barriers to cervical cancer screening, focusing on religious and cultural factors, in order to inform group-specific interventions that may improve uptake of cervical cancer screening programmes. Design We conducted four focus group discussions among Muslim and Christian women in Nigeria. Setting Discussions were conducted in two hospitals, one in the South West and the other in the North Central region of Nigeria. Participants 27 Christian and 22 Muslim women over the age of 18, with no diagnosis of cancer. Results Most participants in the focus group discussions had heard about cervical cancer except Muslim women in the South Western region who had never heard about cervical cancer. Participants believed that wizardry, multiple sexual partners and inserting herbs into the vagina cause cervical cancer. Only one participant knew about the human papillomavirus. Among the Christian women, the majority of respondents had heard about cervical cancer screening and believed that it could be used to prevent cervical cancer. Participants mentioned religious and cultural obligations of modesty, gender of healthcare providers, fear of disclosure of results, fear of nosocomial infections, lack of awareness, discrimination at hospitals, and need for spousal approval as barriers to uptake of screening. These barriers varied by religion across the geographical regions. Conclusions Barriers to cervical cancer screening vary by religious affiliations. Interventions to increase cervical cancer awareness and screening uptake in multicultural and multireligious communities need to take into consideration the varying cultural and religious beliefs in order to design and implement effective cervical cancer screening intervention programmes.

Description: C-reactive protein (CRP) is an acute phase reactant protein produced primarily by the liver. Circulating CRP levels are influenced by genetic and non-genetic factors, including infection and obesity. Genome-wide association studies (GWAS) provide an unbiased approach towards identifying loci influencing CRP levels. None of the six GWAS for CRP levels has been conducted in an African ancestry population. The present study aims to: (i) identify genetic variants that influence serum CRP in African Americans (AA) using a genome-wide association approach and replicate these findings in West Africans (WA), (ii) assess transferability of major signals for CRP reported in European ancestry populations (EA) to AA and (iii) use the weak linkage disequilibrium (LD) structure characteristic of African ancestry populations to fine-map the previously reported CRP locus. The discovery cohort comprised 837 unrelated AA, with the replication of significant single-nucleotide polymorphisms (SNPs) assessed in 486 WA. The association analysis was conducted with 2 366 856 genotyped and imputed SNPs under an additive genetic model with adjustment for appropriate covariates. Genome-wide and replication significances were set at P 〈 5 x 10 –8 and P 〈 0.05, respectively. Ten SNPs in ( CRP pseudogene-1 ) CRPP1 and CRP genes were associated with serum CRP ( P = 2.4 x 10 –09 to 4.3 x 10 –11 ). All but one of the top-scoring SNPs associated with CRP in AA were successfully replicated in WA. CRP signals previously identified in EA samples were transferable to AAs, and we were able to fine-map this signal, reducing the region of interest from the 25 kb of LD around the locus in the HapMap CEU sample to only 8 kb in our AA sample.