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Xiuchan Guo,
Randall C Johnson,
Hong Deng,
Jian Liao,
Li Guan,
George W Nelson,
Mingzhong Tang,
Yuming Zheng, Guy de The,
Stephen J O'Brien,
Cheryl A Winkler,
Yi Zeng
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ABSTRACT: To understand the role of environmental and genetic influences on nasopharyngeal carcinoma (NPC) in populations at high risk of NPC, we have performed a case-control study in Guangxi Province of Southern China in 2004-2005. NPC cases (n = 1,049) were compared with 785 NPC-free matched controls who were seropositive for IgA antibodies (IgA) to Epstein-Barr virus (EBV) capsid antigen (VCA)-a predictive marker for NPC in Chinese populations. A questionnaire was used to capture exposure and NPC family history data. Risk factors associated with NPC in a multivariant analysis model were the following: (i) a first, second or third degree relative with NPC [attributable risk (AR)= 6%, odds ratio (OR) = 3.1, 95% confidence interval (CI) = 2.0-4.9, p < 0.001]; (ii) consumption of salted fish 3 or more than 3 times per month (AR = 3%, OR = 1.9, 95% CI = 1.1-3.5, p = 0.035); (iii) exposure to domestic wood cooking fires for more than 10 years (AR = 69%, OR = 5.8, 95% CI = 2.5-13.6, p < 0.001); and (iv) exposure to occupational solvents for 10 or less years (AR = 4%, OR = 2.6, 95% CI = 1.4-4.8, p = 0.002). Consumption of preserved meats or a history of tobacco smoking were not associated with NPC (p > 0.05). We also assessed the contribution of EBV/IgA/VCA antibody serostatus to NPC risk-32.2% of NPC can be explained by IgA+ status. However, family history and environmental risk factors cumulatively explained only 2.7% of NPC development in NPC high risk population. These findings should have important public health implications for NPC risk reduction in endemic regions.
International Journal of Cancer 01/2009; 124(12):2942-7. · 5.44 Impact Factor
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Xiu Chan Guo,
Kevin Scott,
Yan Liu,
Michael Dean,
Victor David,
George W Nelson,
Randall C Johnson,
Holli H Dilks,
James Lautenberger,
Bailey Kessing,
Janice Martenson,
Li Guan,
Shan Sun,
Hong Deng,
Yuming Zheng, Guy de The,
Jian Liao,
Yi Zeng,
Stephen J O'Brien,
Cheryl A Winkler
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ABSTRACT: Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample handling. A microsatellite screen of Phase I study participants, genotyped for 319 alleles from 34 microsatellites spanning an 18-megabase region of chromosome 4 (4p15.1-q12), previously implicated by a linkage analysis of familial NPC, found 14 alleles marginally associated with developing NPC or chronic immunoglobulin A production (p=0.001-0.03). These associations lost significance after applying a correction for multiple tests. Although the present results await confirmation, the Phase II study population has tripled patient enrollment and has included environmental covariates, offering the potential to validate this and other genomic regions that influence the onset of NPC.
Human genomics 07/2006; 2(6):365-75.
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Emily C Walsh,
Pardis Sabeti,
Holli B Hutcheson,
Ben Fry,
Stephen F Schaffner,
Paul I W de Bakker,
Patrick Varilly,
Alejandro A Palma,
Jessica Roy,
Richard Cooper,
Cheryl Winkler,
Yi Zeng, Guy de The,
Eric S Lander,
Stephen O'Brien,
David Altshuler
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ABSTRACT: Pathogens have played a substantial role in human evolution, with past infections shaping genetic variation at loci influencing immune function. We selected 168 genes known to be involved in the immune response, genotyped common single nucleotide polymorphisms across each gene in three population samples (CEPH Europeans from Utah, Han Chinese from Guangxi, and Yoruba Nigerians from Southwest Nigeria) and searched for evidence of selection based on four tests for non-neutral evolution: minor allele frequency (MAF), derived allele frequency (DAF), Fst versus heterozygosity and extended haplotype homozygosity (EHH). Six of the 168 genes show some evidence for non-neutral evolution in this initial screen, with two showing similar signals in independent data from the International HapMap Project. These analyses identify two loci involved in immune function that are candidates for having been subject to evolutionary selection, and highlight a number of analytical challenges in searching for selection in genome-wide polymorphism data.
Human Genetics 04/2006; 119(1-2):92-102. · 5.07 Impact Factor
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Michael W Smith,
Nick Patterson,
James A Lautenberger,
Ann L Truelove,
Gavin J McDonald,
Alicja Waliszewska,
Bailey D Kessing,
Michael J Malasky,
Charles Scafe,
Ernest Le, [......],
Sarah A Tishkoff,
Cheryl A Winkler,
Francisco M De La Vega,
Trevor Woodage,
John J Sninsky,
David A Hafler,
David Altshuler,
Dennis A Gilbert,
Stephen J O'Brien,
David Reich
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ABSTRACT: Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with approximately 100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing approximately 450000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples. We experimentally confirmed the frequencies of the most promising SNPs in a multiethnic panel of unrelated samples and identified 3011 as a MALD map (1.2 cM average spacing). We estimate that this map is approximately 70% informative in differentiating African versus European origins of chromosomal segments. This map provides a practical and powerful tool, which is freely available without restriction, for screening for disease genes in African American patient cohorts. The map is especially appropriate for those diseases that differ in incidence between the parental African and European populations.
The American Journal of Human Genetics 06/2004; 74(5):1001-13. · 10.60 Impact Factor
