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Replication and Functional Genomic Analyses of the Breast Cancer Susceptibility Locus at 6q25.1 Generalize Its Importance in Women of Chinese, Japanese, and European Ancestry

Cai, Qiuyin ; Wen, Wanqing ; Qu, Shimian ; [et al.]

American Association for Cancer Research (AACR) ; 2011

In: Cancer Research Vol. 71, No. 4 ( 2011-02-15), p. 1344-1355

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In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 4 ( 2011-02-15), p. 1344-1355

Abstract: We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22–1.38) and 1.64 (1.50–1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10−30], Japanese women [ORs (95% CI) = 1.31 (1.13–1.52) and 1.37 (1.06–1.76), P for trend = 2.51 × 10−4] , and European-ancestry American women [ORs (95% CI) = 1.07 (0.99–1.16) and 1.18 (1.04–1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63–1.06) and 0.85 (0.65–1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027] . In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r2 = 0.91) and European-ancestry (r2 = 0.83) populations, but not in Africans (r2 = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region. Cancer Res; 71(4); 1344–55. ©2011 AACR.

Type of Medium: Online Resource

ISSN: 0008-5472 , 1538-7445

URL: Article

DOI: 10.1158/0008-5472.CAN-10-2733

RVK:

XA 36000

RVK:

XA 10000

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2011

detail.hit.zdb_id: 2036785-5

detail.hit.zdb_id: 1432-1

detail.hit.zdb_id: 410466-3

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Pathway Analyses Identify TGFBR2 as Potential Breast Cancer Susceptibility Gene: Results from a Consortium Study among Asians

Ma, Xiangyu ; Beeghly-Fadiel, Alicia ; Lu, Wei ; [et al.]

American Association for Cancer Research (AACR) ; 2012

In: Cancer Epidemiology, Biomarkers & Prevention Vol. 21, No. 7 ( 2012-07-01), p. 1176-1184

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In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 21, No. 7 ( 2012-07-01), p. 1176-1184

Abstract: Background: The TGF-β signaling pathway plays a significant role in the carcinogenic process of breast cancer. Methods: We systematically evaluated associations of common variants in TGF-β signaling pathway genes with breast cancer risk using a multistage, case–control study among Asian women. Results: In the first stage, 341 single-nucleotide polymorphisms with minor allele frequencies ≥ 0.05 across 11 genes were evaluated among 2,926 cases and 2,380 controls recruited as a part of the Shanghai Breast Cancer Genetics Study (SBCGS). In the second stage, 20 SNPs with promising associations were evaluated among an additional 1,890 cases and 2,000 controls from the SBCGS. One variant, TGFBR2 rs1078985, had highly consistent and significant associations with breast cancer risk among participants in both study stages, as well as promising results from in silico analysis. Additional genotyping was carried out among 2,475 cases and 2,343 controls from the SBCGS, as well as among 5,077 cases and 5,384 controls from six studies in the Asian Breast Cancer Consortium (stage III). Pooled analysis of all data indicated that minor allele homozygotes (GG) of TGFBR2 rs1078985 had a 24% reduced risk of breast cancer compared with major allele carriers (AG or AA; OR, 0.76; 95% CI, 0.65–0.89; P = 8.42 × 10−4). Conclusion: These findings support a role for common genetic variation in TGF-β signaling pathway genes, specifically in TGFBR2, in breast cancer susceptibility. Impact: These findings may provide new insights into the etiology of breast cancer as well as future potential therapeutic targets. Cancer Epidemiol Biomarkers Prev; 21(7); 1176–84. ©2012 AACR.

Type of Medium: Online Resource

ISSN: 1055-9965 , 1538-7755

URL: Article

DOI: 10.1158/1055-9965.EPI-12-0118

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2012

detail.hit.zdb_id: 2036781-8

detail.hit.zdb_id: 1153420-5

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New Breast Cancer Risk Variant Discovered at 10q25 in East Asian Women

Shi, Jiajun ; Sung, Hyuna ; Zhang, Ben ; [et al.]

American Association for Cancer Research (AACR) ; 2013

In: Cancer Epidemiology, Biomarkers & Prevention Vol. 22, No. 7 ( 2013-07-01), p. 1297-1303

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In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 22, No. 7 ( 2013-07-01), p. 1297-1303

Abstract: Background: Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study (GWAS) conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations. Methods: We evaluated nine of those nonreplication loci in East Asians to identify new risk variants for breast cancer in these regions. First, we analyzed single-nucleotide polymorphisms (SNP) in these regions using data from two GWAS conducted among Chinese and Korean women, including 5,083 cases and 4,376 controls (stage 1). In each region, we selected an SNP showing the strongest association with breast cancer risk for replication in an independent set of 7,294 cases and 9,404 controls of East Asian descents (stage 2). Logistic regression models were used to calculate adjusted ORs and 95% confidence intervals (CI) as a measure of the association of breast cancer risk and genetic variants. Results: Two SNPs were replicated in stage 2 at P & lt; 0.05: rs1419026 at 6q14 [per allele OR, 1.07; 95% confidence interval (CI), 1.03–1.12; P = 3.0 × 10−4] and rs941827 at 10q25 (OR, 0.92, 95% CI, 0.89–0.96; P = 5.3 × 10−5). The association with rs941827 remained highly statistically significant after adjusting for the risk variant identified initially in women of European ancestry (OR, 0.88; 95% CI, 0.82–0.97; P = 5.3 × 10−5). Conclusion: We identified a new breast cancer risk variant at 10q25 in East Asian women. Impact: Results from this study improve the understanding of the genetic basis for breast cancer. Cancer Epidemiol Biomarkers Prev; 22(7); 1297–303. ©2013 AACR.

Type of Medium: Online Resource

ISSN: 1055-9965 , 1538-7755

URL: Article

DOI: 10.1158/1055-9965.EPI-12-1393

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2013

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detail.hit.zdb_id: 1153420-5

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