Pub Date : 2014-05-01DOI: 10.1016/S0016-5085(14)63524-1
D. White, Yanhong Liu, Jose M Garcia, H. El‐Serag, L. Jiao, S. Tsavachidis, L. M. Franco, Ju-Seog Lee, S. Tavakoli-Tabasi, D. Moore, R. Goldman, Jill Kuzniarek, D. Ramsey, F. Kanwal, M. Marcelli
{"title":"Sex hormone pathway gene polymorphisms are associated with risk of advanced hepatitis C-related liver disease in males.","authors":"D. White, Yanhong Liu, Jose M Garcia, H. El‐Serag, L. Jiao, S. Tsavachidis, L. M. Franco, Ju-Seog Lee, S. Tavakoli-Tabasi, D. Moore, R. Goldman, Jill Kuzniarek, D. Ramsey, F. Kanwal, M. Marcelli","doi":"10.1016/S0016-5085(14)63524-1","DOIUrl":"https://doi.org/10.1016/S0016-5085(14)63524-1","url":null,"abstract":"","PeriodicalId":73460,"journal":{"name":"International journal of molecular epidemiology and genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0016-5085(14)63524-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55794803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Astrid Suchy-Dicey, Susan R Heckbert, Nicholas L Smith, Barbara McKnight, Jerome I Rotter, Yd Ida Chen, Bruce M Psaty, Daniel A Enquobahrie
Thiazide diuretics and statins are used to improve cardiovascular outcomes, but may also cause type 2 diabetes (T2DM), although mechanisms are unknown. Gene expression studies may facilitate understanding of these associations. Participants from ongoing population-based studies were sampled for these longitudinal studies of peripheral blood microarray gene expression, and followed to incident diabetes. All sampled subjects were statin or thiazide users. Those who developed diabetes during follow-up comprised cases (44 thiazide users; 19 statin users), and were matched to drug-using controls who did not develop diabetes on several factors. Supervised normalization, surrogate variable analyses removed technical bias and confounding. Differentially-expressed genes were those with a false discovery rate Q-value<0.05. Among thiazide users, diabetes cases had significantly different expression of CCL14 (down-regulated 6%, Q-value=0.0257), compared with controls. Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls. These genes comprise potential targets for future expression or mechanistic research on medication-related diabetes development.
{"title":"Gene expression in thiazide diuretic or statin users in relation to incident type 2 diabetes.","authors":"Astrid Suchy-Dicey, Susan R Heckbert, Nicholas L Smith, Barbara McKnight, Jerome I Rotter, Yd Ida Chen, Bruce M Psaty, Daniel A Enquobahrie","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Thiazide diuretics and statins are used to improve cardiovascular outcomes, but may also cause type 2 diabetes (T2DM), although mechanisms are unknown. Gene expression studies may facilitate understanding of these associations. Participants from ongoing population-based studies were sampled for these longitudinal studies of peripheral blood microarray gene expression, and followed to incident diabetes. All sampled subjects were statin or thiazide users. Those who developed diabetes during follow-up comprised cases (44 thiazide users; 19 statin users), and were matched to drug-using controls who did not develop diabetes on several factors. Supervised normalization, surrogate variable analyses removed technical bias and confounding. Differentially-expressed genes were those with a false discovery rate Q-value<0.05. Among thiazide users, diabetes cases had significantly different expression of CCL14 (down-regulated 6%, Q-value=0.0257), compared with controls. Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls. These genes comprise potential targets for future expression or mechanistic research on medication-related diabetes development. </p>","PeriodicalId":73460,"journal":{"name":"International journal of molecular epidemiology and genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939004/pdf/ijmeg0005-0022.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40285037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cecilia Bobillo, Julio A Navoni, Valentina Olmos, Luciano J Merini, Edda Villaamil Lepori, Daniel Corach
Because the ratio between the two major arsenic metabolites is related to the adverse health effects of arsenic, numerous studies have been performed to establish a relationship between the ability to metabolically detoxify arsenic and other variables, including exposure level, gender, age and ethnicity. Because ethnicity may play a key role and provide relevant information for heterogeneous populations, we characterized a group of 70 children from rural schools in the Argentinean provinces of Chaco and Santiago del Estero who were exposed to high levels of arsenic. We used genetic markers for maternal, paternal and bi-parental ancestry to achieve this goal. Our results demonstrate that the Amerindian maternal linages are present in 100% of the samples, whereas the Amerindian component transmitted through the paternal line is less than 10%. Informative markers for autosomal ancestry show a predominantly European ancestry, in which 37% of the samples contained between 90 and 99% European ancestry. The native American component ranged from 50 to 80% in 15.7% of the samples, and in all but four samples, the African component was less than 10%. Correlation analysis demonstrated that the ethnicity and the ratio of the excreted arsenic metabolites monomethyl arsenic and dimethyl arsenic are not associated, dismissing a relationship between ethnic origin and differential metabolism.
{"title":"Ethnic characterization of a population of children exposed to high doses of arsenic via drinking water and a possible correlation with metabolic processes.","authors":"Cecilia Bobillo, Julio A Navoni, Valentina Olmos, Luciano J Merini, Edda Villaamil Lepori, Daniel Corach","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Because the ratio between the two major arsenic metabolites is related to the adverse health effects of arsenic, numerous studies have been performed to establish a relationship between the ability to metabolically detoxify arsenic and other variables, including exposure level, gender, age and ethnicity. Because ethnicity may play a key role and provide relevant information for heterogeneous populations, we characterized a group of 70 children from rural schools in the Argentinean provinces of Chaco and Santiago del Estero who were exposed to high levels of arsenic. We used genetic markers for maternal, paternal and bi-parental ancestry to achieve this goal. Our results demonstrate that the Amerindian maternal linages are present in 100% of the samples, whereas the Amerindian component transmitted through the paternal line is less than 10%. Informative markers for autosomal ancestry show a predominantly European ancestry, in which 37% of the samples contained between 90 and 99% European ancestry. The native American component ranged from 50 to 80% in 15.7% of the samples, and in all but four samples, the African component was less than 10%. Correlation analysis demonstrated that the ethnicity and the ratio of the excreted arsenic metabolites monomethyl arsenic and dimethyl arsenic are not associated, dismissing a relationship between ethnic origin and differential metabolism. </p>","PeriodicalId":73460,"journal":{"name":"International journal of molecular epidemiology and genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939002/pdf/ijmeg0005-0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40285035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Uirá S Melo, Silvana Santos, Hannalice G Cavalcanti, Wagner T Andrade, Vitor G Dantas, Marine Rd Rosa, Regina C Mingroni-Netto
The overall aim of this study was to estimate the contribution of genetic factors to the etiology of hearing loss (HL) in two counties in the Brazilian northeastern region. A cross-sectional study, based on the key informant approach (KI) was conducted in Queimadas and Gado Bravo counties (Paraíba, Northeast Brazil). The sample consisted of 182 patients with HL. Genetic screening of the most frequent mutations associated with HL was performed for all samples. DFNB1 mutations were the most frequently found in both counties. The c.35delG mutation was detected in homozygosis in seven non-syndromic probands in Queimadas (7/76, 9.2%) and only a single homozygote with this mutation was found in Gado Bravo (1/44, 2.3%). We also detected the del(GJB6-D13S1854) mutation in non-syndromic probands from Gado Bravo (2/44, 4.5%). The c.189C>A (p.TyrY63*) mutation in the CLRN1 gene was detected in homozygosis in 21/23 Usher syndrome patients from Gado Bravo and it was not found in Queimadas. Cases with probable genetic etiology contributed approximately to half of HL probands in each county (54.6% in Gado Bravo and 45.7% in Queimadas). We confirm the importance of DFNB1 locus to non-syndromic HL but we show that the frequency of mutations in the northeastern region differs somewhat from those reported in southeastern Brazil and other populations. In addition, the extremely high frequency of individuals with Usher syndrome with c.189C>A variation in CLRN1 indicates the need for a specific screening of this mutation.
{"title":"Strategies for genetic study of hearing loss in the Brazilian northeastern region.","authors":"Uirá S Melo, Silvana Santos, Hannalice G Cavalcanti, Wagner T Andrade, Vitor G Dantas, Marine Rd Rosa, Regina C Mingroni-Netto","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The overall aim of this study was to estimate the contribution of genetic factors to the etiology of hearing loss (HL) in two counties in the Brazilian northeastern region. A cross-sectional study, based on the key informant approach (KI) was conducted in Queimadas and Gado Bravo counties (Paraíba, Northeast Brazil). The sample consisted of 182 patients with HL. Genetic screening of the most frequent mutations associated with HL was performed for all samples. DFNB1 mutations were the most frequently found in both counties. The c.35delG mutation was detected in homozygosis in seven non-syndromic probands in Queimadas (7/76, 9.2%) and only a single homozygote with this mutation was found in Gado Bravo (1/44, 2.3%). We also detected the del(GJB6-D13S1854) mutation in non-syndromic probands from Gado Bravo (2/44, 4.5%). The c.189C>A (p.TyrY63*) mutation in the CLRN1 gene was detected in homozygosis in 21/23 Usher syndrome patients from Gado Bravo and it was not found in Queimadas. Cases with probable genetic etiology contributed approximately to half of HL probands in each county (54.6% in Gado Bravo and 45.7% in Queimadas). We confirm the importance of DFNB1 locus to non-syndromic HL but we show that the frequency of mutations in the northeastern region differs somewhat from those reported in southeastern Brazil and other populations. In addition, the extremely high frequency of individuals with Usher syndrome with c.189C>A variation in CLRN1 indicates the need for a specific screening of this mutation. </p>","PeriodicalId":73460,"journal":{"name":"International journal of molecular epidemiology and genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939003/pdf/ijmeg0005-0011.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40285036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Omar F Khabour, Abdulfattah S Fararjeh, Almuthana A Alfaouri
The azoospermia factor (AZF) region of the human Y chromosome contains essential genes for spermatogenesis. Microdeletions in AZF region has been shown to cause male infertility. The aim of this investigation was to determine the frequency of AZF microdeletions in Jordanian infertile males. A sample of 100 infertile males (36 with azoospermia and 64 with oligozoospermia) was screened for microdeletions using 16 AZF markers and polymerase chain reaction (PCR) technique. Two subjects were found to have microdeletions in AZFc region and one subject has microdeletion that includes AZFb and part of AZFc and AZFa. The three deletions were found in azoospermic subjects (8.3%). No microdeletions were found in oligozoospermic group. The frequency of AZF microdeletions in Jordanian azoospermic infertile males is comparable to that observed in other populations (1%-15%). The results suggest the importance of AZF microdeletion analysis for genetic counseling prior to providing assisted reproduction technique.
{"title":"Genetic screening for AZF Y chromosome microdeletions in Jordanian azoospermic infertile men.","authors":"Omar F Khabour, Abdulfattah S Fararjeh, Almuthana A Alfaouri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The azoospermia factor (AZF) region of the human Y chromosome contains essential genes for spermatogenesis. Microdeletions in AZF region has been shown to cause male infertility. The aim of this investigation was to determine the frequency of AZF microdeletions in Jordanian infertile males. A sample of 100 infertile males (36 with azoospermia and 64 with oligozoospermia) was screened for microdeletions using 16 AZF markers and polymerase chain reaction (PCR) technique. Two subjects were found to have microdeletions in AZFc region and one subject has microdeletion that includes AZFb and part of AZFc and AZFa. The three deletions were found in azoospermic subjects (8.3%). No microdeletions were found in oligozoospermic group. The frequency of AZF microdeletions in Jordanian azoospermic infertile males is comparable to that observed in other populations (1%-15%). The results suggest the importance of AZF microdeletion analysis for genetic counseling prior to providing assisted reproduction technique. </p>","PeriodicalId":73460,"journal":{"name":"International journal of molecular epidemiology and genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939006/pdf/ijmeg0005-0047.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40285039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intrafamilial spread of hepatitis B virus: some comments.","authors":"Ali Kabir, Mehrdad Moghimi, Afshin Amini","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":73460,"journal":{"name":"International journal of molecular epidemiology and genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939007/pdf/ijmeg0005-0051.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40285040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Wang, Sue Ann Ingles, Gabriela Torres-Mejía, Mariana C Stern, Frank Z Stanczyk, Gary G Schwartz, David O Nelson, Laura Fejerman, Roger K Wolff, Martha L Slattery, Esther M John
Genome-wide association studies (GWAS) have identified common polymorphisms in or near GC, CYP2R1, CYP24A1, and NADSYN1/DHCR7 genes to be associated with circulating levels of 25-hydroxyvitamin D [25(OH)D] in European populations. To replicate these GWAS findings, we examined six selected polymorphisms from these regions and their relation with circulating 25(OH)D levels in 1,605 Hispanic women (629 U.S. Hispanics and 976 Mexicans) and 354 non-Hispanic White (NHW) women. We also assessed the potential interactions between these variants and known non-genetic predictors of 25(OH)D levels, including body mass index (BMI), sunlight exposure and vitamin D intake from diet and supplements. The minor alleles of the two GC polymorphisms (rs7041 and rs2282679) were significantly associated with lower 25(OH)D levels in both Hispanic and NHW women. The CYP2R1 polymorphism, rs2060793, also was significantly associated with 25(OH)D levels in both groups. We found no significant associations for the polymorphisms in the CYP24A1. In Hispanic controls, 25(OH)D levels were significantly associated with the rs12785878T and rs1790349G haplotype in the NADSYN1/DHCR7 region. Significant interactions between GC rs2282679 and BMI and between rs12785878 and time spent in outdoor activities were observed. These results provide further support for the contribution of common genetic variants to individual variability in circulating 25(OH)D levels. The observed interactions between SNPs and non-genetic factors warrant confirmation.
{"title":"Genetic variants and non-genetic factors predict circulating vitamin D levels in Hispanic and non-Hispanic White women: the Breast Cancer Health Disparities Study.","authors":"Wei Wang, Sue Ann Ingles, Gabriela Torres-Mejía, Mariana C Stern, Frank Z Stanczyk, Gary G Schwartz, David O Nelson, Laura Fejerman, Roger K Wolff, Martha L Slattery, Esther M John","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) have identified common polymorphisms in or near GC, CYP2R1, CYP24A1, and NADSYN1/DHCR7 genes to be associated with circulating levels of 25-hydroxyvitamin D [25(OH)D] in European populations. To replicate these GWAS findings, we examined six selected polymorphisms from these regions and their relation with circulating 25(OH)D levels in 1,605 Hispanic women (629 U.S. Hispanics and 976 Mexicans) and 354 non-Hispanic White (NHW) women. We also assessed the potential interactions between these variants and known non-genetic predictors of 25(OH)D levels, including body mass index (BMI), sunlight exposure and vitamin D intake from diet and supplements. The minor alleles of the two GC polymorphisms (rs7041 and rs2282679) were significantly associated with lower 25(OH)D levels in both Hispanic and NHW women. The CYP2R1 polymorphism, rs2060793, also was significantly associated with 25(OH)D levels in both groups. We found no significant associations for the polymorphisms in the CYP24A1. In Hispanic controls, 25(OH)D levels were significantly associated with the rs12785878T and rs1790349G haplotype in the NADSYN1/DHCR7 region. Significant interactions between GC rs2282679 and BMI and between rs12785878 and time spent in outdoor activities were observed. These results provide further support for the contribution of common genetic variants to individual variability in circulating 25(OH)D levels. The observed interactions between SNPs and non-genetic factors warrant confirmation. </p>","PeriodicalId":73460,"journal":{"name":"International journal of molecular epidemiology and genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939005/pdf/ijmeg0005-0031.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40285038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hien Tt Luong, Jodie N Painter, Konstantin Shakhbazov, Brett Chapman, Anjali K Henders, Joseph E Powell, Dale R Nyholt, Grant W Montgomery
Genome-wide association studies show strong evidence of association with endometriosis for markers on chromosome 1p36 spanning the potential candidate genes WNT4, CDC42 and LINC00339. WNT4 is involved in development of the uterus, and the expression of CDC42 and LINC00339 are altered in women with endometriosis. We conducted fine mapping to examine the role of coding variants in WNT4 and CDC42 and determine the key SNPs with strongest evidence of association in this region. We identified rare coding variants in WNT4 and CDC42 present only in endometriosis cases. The frequencies were low and cannot account for the common signal associated with increased risk of endometriosis. Genotypes for five common SNPs in the region of chromosome 1p36 show stronger association signals when compared with rs7521902 reported in published genome scans. Of these, three SNPs rs12404660, rs3820282, and rs55938609 were located in DNA sequences with potential functional roles including overlap with transcription factor binding sites for FOXA1, FOXA2, ESR1, and ESR2. Functional studies will be required to identify the gene or genes implicated in endometriosis risk.
{"title":"Fine mapping of variants associated with endometriosis in the WNT4 region on chromosome 1p36.","authors":"Hien Tt Luong, Jodie N Painter, Konstantin Shakhbazov, Brett Chapman, Anjali K Henders, Joseph E Powell, Dale R Nyholt, Grant W Montgomery","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genome-wide association studies show strong evidence of association with endometriosis for markers on chromosome 1p36 spanning the potential candidate genes WNT4, CDC42 and LINC00339. WNT4 is involved in development of the uterus, and the expression of CDC42 and LINC00339 are altered in women with endometriosis. We conducted fine mapping to examine the role of coding variants in WNT4 and CDC42 and determine the key SNPs with strongest evidence of association in this region. We identified rare coding variants in WNT4 and CDC42 present only in endometriosis cases. The frequencies were low and cannot account for the common signal associated with increased risk of endometriosis. Genotypes for five common SNPs in the region of chromosome 1p36 show stronger association signals when compared with rs7521902 reported in published genome scans. Of these, three SNPs rs12404660, rs3820282, and rs55938609 were located in DNA sequences with potential functional roles including overlap with transcription factor binding sites for FOXA1, FOXA2, ESR1, and ESR2. Functional studies will be required to identify the gene or genes implicated in endometriosis risk. </p>","PeriodicalId":73460,"journal":{"name":"International journal of molecular epidemiology and genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852639/pdf/ijmeg0004-0193.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31938177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Avonne E Connor, Richard N Baumgartner, Kathy B Baumgartner, Christina M Pinkston, Esther M John, Gabriela Torres-Mejía, Lisa M Hines, Anna R Giuliano, Roger K Wolff, Martha L Slattery
The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, functions in cellular processes essential to the development of cancer. Overexpression of EGFR in primary breast tumors has been linked with poor prognosis. We investigated the associations between 34 EGFR tagging SNPs and breast cancer risk and breast cancer-specific mortality in 4,703 Hispanic and 3,030 non-Hispanic white women from the Breast Cancer Health Disparities Study. We evaluated associations with risk of breast cancer defined by estrogen/progesterone receptor (ER/PR) tumor phenotype. Only one association remained statistically significant after adjusting for multiple comparisons. Rs2075112GA/AA was associated with reduced risk for ER-/PR+ tumor phenotype (odds ratio (OR), 0.34; 95% confidence interval (CI) 0.18-0.63, p adj=0.01). All additional results were significant prior to adjustment for multiple comparisons. Two of the EGFR polymorphisms were associated with breast cancer risk in the overall study population (rs11770531TT: OR, 0.56, 95% CI 0.37-0.84; and rs2293348AA: OR, 1.20, 95% CI 1.04-1.38) and two polymorphisms were associated with risk among Hispanics: rs6954351AA: OR, 2.50, 95% CI 1.32-4.76; and rs845558GA/AA: OR, 1.15, 95% CI 1.01-1.30. With regard to breast cancer-specific mortality, we found positive associations with rs6978771TT hazard ratio (HR), 1.68; 95% CI 1.11-2.56; rs9642391CC HR, 1.64; 95% CI 1.04-2.58; rs4947979AG/GG HR, 1.36; 95% CI 1.03-1.79; and rs845552GG HR, 1.62; 95% CI 1.05-2.49. Our findings provide additional insight for the role of EGFR in breast cancer development and prognosis. Further research is needed to elucidate EGFR's contribution to ethnic disparities in breast cancer.
表皮生长因子受体(EGFR)是ErbB受体酪氨酸激酶家族的一员,在癌症发生的细胞过程中发挥重要作用。原发性乳腺肿瘤中EGFR的过表达与预后不良有关。我们调查了来自乳腺癌健康差异研究的4703名西班牙裔和3030名非西班牙裔白人女性中34个EGFR标记snp与乳腺癌风险和乳腺癌特异性死亡率之间的关系。我们评估了雌激素/孕激素受体(ER/PR)肿瘤表型与乳腺癌风险的关系。在调整多重比较后,只有一种关联仍然具有统计学意义。Rs2075112GA/AA与ER-/PR+肿瘤表型风险降低相关(优势比(OR), 0.34;95%置信区间(CI) 0.18-0.63, p adj=0.01)。在对多重比较进行调整之前,所有其他结果都是显著的。在整个研究人群中,两种EGFR多态性与乳腺癌风险相关(rs11770531TT: OR, 0.56, 95% CI 0.37-0.84;rs2293348AA: OR, 1.20, 95% CI 1.04-1.38)和两个多态性与西班牙裔人群的风险相关:rs6954351AA: OR, 2.50, 95% CI 1.32-4.76;rs845558GA/AA: OR, 1.15, 95% CI 1.01-1.30。关于乳腺癌特异性死亡率,我们发现与rs6978771TT风险比(HR)呈正相关,为1.68;95% ci 1.11-2.56;rs9642391CC HR, 1.64;95% ci 1.04-2.58;rs4947979AG/GG HR, 1.36;95% ci 1.03-1.79;rs845552GG HR, 1.62;95% ci 1.05-2.49。我们的发现为EGFR在乳腺癌发展和预后中的作用提供了额外的见解。需要进一步的研究来阐明EGFR在乳腺癌种族差异中的作用。
{"title":"Epidermal growth factor receptor (EGFR) polymorphisms and breast cancer among Hispanic and non-Hispanic white women: the Breast Cancer Health Disparities Study.","authors":"Avonne E Connor, Richard N Baumgartner, Kathy B Baumgartner, Christina M Pinkston, Esther M John, Gabriela Torres-Mejía, Lisa M Hines, Anna R Giuliano, Roger K Wolff, Martha L Slattery","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, functions in cellular processes essential to the development of cancer. Overexpression of EGFR in primary breast tumors has been linked with poor prognosis. We investigated the associations between 34 EGFR tagging SNPs and breast cancer risk and breast cancer-specific mortality in 4,703 Hispanic and 3,030 non-Hispanic white women from the Breast Cancer Health Disparities Study. We evaluated associations with risk of breast cancer defined by estrogen/progesterone receptor (ER/PR) tumor phenotype. Only one association remained statistically significant after adjusting for multiple comparisons. Rs2075112GA/AA was associated with reduced risk for ER-/PR+ tumor phenotype (odds ratio (OR), 0.34; 95% confidence interval (CI) 0.18-0.63, p adj=0.01). All additional results were significant prior to adjustment for multiple comparisons. Two of the EGFR polymorphisms were associated with breast cancer risk in the overall study population (rs11770531TT: OR, 0.56, 95% CI 0.37-0.84; and rs2293348AA: OR, 1.20, 95% CI 1.04-1.38) and two polymorphisms were associated with risk among Hispanics: rs6954351AA: OR, 2.50, 95% CI 1.32-4.76; and rs845558GA/AA: OR, 1.15, 95% CI 1.01-1.30. With regard to breast cancer-specific mortality, we found positive associations with rs6978771TT hazard ratio (HR), 1.68; 95% CI 1.11-2.56; rs9642391CC HR, 1.64; 95% CI 1.04-2.58; rs4947979AG/GG HR, 1.36; 95% CI 1.03-1.79; and rs845552GG HR, 1.62; 95% CI 1.05-2.49. Our findings provide additional insight for the role of EGFR in breast cancer development and prognosis. Further research is needed to elucidate EGFR's contribution to ethnic disparities in breast cancer. </p>","PeriodicalId":73460,"journal":{"name":"International journal of molecular epidemiology and genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852643/pdf/ijmeg0004-0235.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31939215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hussein A Basma, Loulou H Kobeissi, Michel E Jabbour, Mohamad A Moussa, Hassan R Dhaini
Urinary bladder cancer incidence in Lebanon ranks among the highest in the world. Cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase1 (NQO1), and N-Acetyltransferase1 (NAT1), are drug-metabolizing enzymes (DMEs) involved in the metabolism of carcinogens, such as arylamines and heterocyclic amines, implicated in bladder cancer. The present study attempts to investigate the role of these DMEs genetic polymorphism in bladder cancer risk among Lebanese men. 54 cases and 106 controls were recruited from two hospitals in Beirut. An interview-based questionnaire was administered to assess suspected environmental and occupational risk factors. PCR-RFLP was performed on blood-based DNA samples to determine DMEs genotypes. Associations between bladder cancer and putative risk factors were measured using adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Results showed CYP2E1 c1/c1, NAT1*14A, and smoking, to be risk factors for bladder cancer. No significant differences in frequency distribution of the NQO1 genotypes were found in cases versus controls. The odds of carrying the CYP2E1 c1/c1 genotype were 4 times higher in cases compared to controls (OR=3.97, 95% CI: 0.48-32.7). The odds of carrying at least one NAT1*14A allele were 14 times higher in cases versus controls (OR=14.4, 95% CI: 1.016-204.9). Our study suggests CYP2E1 c1/c1, NAT1*14A, and smoking, as potential risk factors for bladder cancer in Lebanese. Further studies with larger samples must be conducted to confirm these findings.
{"title":"CYP2E1 and NQO1 genotypes and bladder cancer risk in a Lebanese population.","authors":"Hussein A Basma, Loulou H Kobeissi, Michel E Jabbour, Mohamad A Moussa, Hassan R Dhaini","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Urinary bladder cancer incidence in Lebanon ranks among the highest in the world. Cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase1 (NQO1), and N-Acetyltransferase1 (NAT1), are drug-metabolizing enzymes (DMEs) involved in the metabolism of carcinogens, such as arylamines and heterocyclic amines, implicated in bladder cancer. The present study attempts to investigate the role of these DMEs genetic polymorphism in bladder cancer risk among Lebanese men. 54 cases and 106 controls were recruited from two hospitals in Beirut. An interview-based questionnaire was administered to assess suspected environmental and occupational risk factors. PCR-RFLP was performed on blood-based DNA samples to determine DMEs genotypes. Associations between bladder cancer and putative risk factors were measured using adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Results showed CYP2E1 c1/c1, NAT1*14A, and smoking, to be risk factors for bladder cancer. No significant differences in frequency distribution of the NQO1 genotypes were found in cases versus controls. The odds of carrying the CYP2E1 c1/c1 genotype were 4 times higher in cases compared to controls (OR=3.97, 95% CI: 0.48-32.7). The odds of carrying at least one NAT1*14A allele were 14 times higher in cases versus controls (OR=14.4, 95% CI: 1.016-204.9). Our study suggests CYP2E1 c1/c1, NAT1*14A, and smoking, as potential risk factors for bladder cancer in Lebanese. Further studies with larger samples must be conducted to confirm these findings. </p>","PeriodicalId":73460,"journal":{"name":"International journal of molecular epidemiology and genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852640/pdf/ijmeg0004-0207.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31938178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}