Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2010

01-11-2010 | Epidemiology

Quantitative assessment of the effect of FGFR2 gene polymorphism on the risk of breast cancer

Authors: Chenyou Jia, Yu Cai, Yushui Ma, Da Fu

Published in: Breast Cancer Research and Treatment | Issue 2/2010

Login to get access

Abstract

Fibroblast growth factor receptor 2 is a tyrosine kinase receptor that is a member of the family of individually distinct fibroblast growth factor receptors involved in cell proliferation, invasiveness, motility, and angiogenesis. Genome-wide association studies have identified FGFR2 as a breast cancer (BC) susceptibility gene in populations of European and Asian descent. After that, a number of studies reported that the rs2981582, rs1219648, and rs2420946 polymorphism in FGFR2 has been implicated in BC risk. However, studies on the association between these polymorphism and BC remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 46,747 cases and 87,342 controls from 16 published case–control studies was performed. Overall, significantly elevated BC risk was associated with rs2981582, rs1219648, and rs2420946 risk allele when all studies were pooled into the meta-analysis. Significant results were also observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the subgroup analysis by ethnicity, source of controls, significantly increased risks were found for these polymorphisms in all genetic model. In conclusion, this meta-analysis suggests that rs2981582, rs1219648, and rs2420946 polymorphisms in FGFR2 are associated with elevated BC risk.
Literature
2.
go back to reference Lichtenstein P, Holm NV, Verkasalo PK et al (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85CrossRefPubMed Lichtenstein P, Holm NV, Verkasalo PK et al (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85CrossRefPubMed
3.
go back to reference Lux MP, Fasching PA, Beckmann MW (2006) Hereditary breast and ovarian cancer: review and future perspectives. J Mol Med 84:16–28CrossRefPubMed Lux MP, Fasching PA, Beckmann MW (2006) Hereditary breast and ovarian cancer: review and future perspectives. J Mol Med 84:16–28CrossRefPubMed
5.
go back to reference Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R et al (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447:1087–1093CrossRefPubMed Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R et al (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447:1087–1093CrossRefPubMed
6.
go back to reference Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Hutchinson A et al (2007) A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet 39:870–874CrossRefPubMed Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Hutchinson A et al (2007) A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet 39:870–874CrossRefPubMed
7.
go back to reference Ricol D et al (1999) Tumour suppressive properties of fibroblast growth factor receptor 2-IIIb in human bladder cancer. Oncogene 18:7234–7243CrossRefPubMed Ricol D et al (1999) Tumour suppressive properties of fibroblast growth factor receptor 2-IIIb in human bladder cancer. Oncogene 18:7234–7243CrossRefPubMed
8.
go back to reference Tannheimer SL et al (2000) Characterization of fibroblast growth factor receptor 2 overexpression in the human breast cancer cell line SUM-52PE. Breast Cancer Res 2:311–320CrossRefPubMed Tannheimer SL et al (2000) Characterization of fibroblast growth factor receptor 2 overexpression in the human breast cancer cell line SUM-52PE. Breast Cancer Res 2:311–320CrossRefPubMed
9.
go back to reference Adnane J et al (1991) BEK and FLG, two receptors to members of the FGF family, are amplified in subsets of human breast cancers. Oncogene 6:659–663PubMed Adnane J et al (1991) BEK and FLG, two receptors to members of the FGF family, are amplified in subsets of human breast cancers. Oncogene 6:659–663PubMed
10.
go back to reference Moffa AB et al (2007) Differential signal transduction of alternatively spliced FGFR2 variants expressed in human mammary epithelial cells. J Cell Physiol 210:720–731CrossRefPubMed Moffa AB et al (2007) Differential signal transduction of alternatively spliced FGFR2 variants expressed in human mammary epithelial cells. J Cell Physiol 210:720–731CrossRefPubMed
11.
go back to reference Koziczak M et al (2004) Blocking of FGFR signaling inhibits breast cancer cell proliferation through down regulation of D-type cyclins. Oncogene 23:3501–3508CrossRefPubMed Koziczak M et al (2004) Blocking of FGFR signaling inhibits breast cancer cell proliferation through down regulation of D-type cyclins. Oncogene 23:3501–3508CrossRefPubMed
12.
go back to reference Lu P et al (2008) Genetic mosaic analysis reveals FGF receptor 2 function in terminal end buds during mammary gland branching morphogenesis. Dev Biol 321:77–87CrossRefPubMed Lu P et al (2008) Genetic mosaic analysis reveals FGF receptor 2 function in terminal end buds during mammary gland branching morphogenesis. Dev Biol 321:77–87CrossRefPubMed
13.
go back to reference Ingersoll RG et al (2001) Fibroblast growth factor receptor 2 (FGFR2): genomic sequence and variations. Cytogenet Cell Genet 94:121–126CrossRefPubMed Ingersoll RG et al (2001) Fibroblast growth factor receptor 2 (FGFR2): genomic sequence and variations. Cytogenet Cell Genet 94:121–126CrossRefPubMed
14.
go back to reference Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefPubMed Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefPubMed
15.
go back to reference Woolf B (1955) On estimating the relation between blood group and disease. Ann Hum Genet 19:251–253CrossRefPubMed Woolf B (1955) On estimating the relation between blood group and disease. Ann Hum Genet 19:251–253CrossRefPubMed
16.
go back to reference Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMed Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMed
17.
go back to reference Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101CrossRefPubMed Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101CrossRefPubMed
18.
go back to reference Antoniou AC, Spurdle AB, Sinilnikova OM et al (2008) Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet 82(4):937–948CrossRefPubMed Antoniou AC, Spurdle AB, Sinilnikova OM et al (2008) Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet 82(4):937–948CrossRefPubMed
19.
go back to reference Garcia-Closas M, Hall P, Nevanlinna H et al (2008) Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet 4(4):e1000054 Garcia-Closas M, Hall P, Nevanlinna H et al (2008) Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet 4(4):e1000054
20.
go back to reference Liang J, Chen P, Hu Z, Zhou X, Chen L, Li M, Wang Y, Tang J, Wang H, Shen H (2008) Genetic variants in fibroblast growth factor receptor 2 (FGFR2) contribute to susceptibility of breast cancer in Chinese women. Carcinogenesis 29(12):2341–2346CrossRefPubMed Liang J, Chen P, Hu Z, Zhou X, Chen L, Li M, Wang Y, Tang J, Wang H, Shen H (2008) Genetic variants in fibroblast growth factor receptor 2 (FGFR2) contribute to susceptibility of breast cancer in Chinese women. Carcinogenesis 29(12):2341–2346CrossRefPubMed
21.
go back to reference Raskin L, Pinchev M, Arad C, Lejbkowicz F, Tamir A, Rennert HS, Rennert G, Gruber SB (2008) FGFR2 is a breast cancer susceptibility gene in Jewish and Arab Israeli populations. Cancer Epidemiol Biomarkers Prev 17(5):1060–1065CrossRefPubMed Raskin L, Pinchev M, Arad C, Lejbkowicz F, Tamir A, Rennert HS, Rennert G, Gruber SB (2008) FGFR2 is a breast cancer susceptibility gene in Jewish and Arab Israeli populations. Cancer Epidemiol Biomarkers Prev 17(5):1060–1065CrossRefPubMed
22.
go back to reference Stacey SN, Manolescu A, Sulem P et al (2008) Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 40(6):703–706CrossRefPubMed Stacey SN, Manolescu A, Sulem P et al (2008) Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 40(6):703–706CrossRefPubMed
23.
go back to reference Boyarskikh UA, Zarubina NA, Biltueva JA, Sinkina TV, Voronina EN, Lazarev AF, Petrova VD, Aulchenko YS, Filipenko ML (2009) Association of FGFR2 gene polymorphisms with the risk of breast cancer in population of West Siberia. Eur J Hum Genet 17(12):1688–1691CrossRefPubMed Boyarskikh UA, Zarubina NA, Biltueva JA, Sinkina TV, Voronina EN, Lazarev AF, Petrova VD, Aulchenko YS, Filipenko ML (2009) Association of FGFR2 gene polymorphisms with the risk of breast cancer in population of West Siberia. Eur J Hum Genet 17(12):1688–1691CrossRefPubMed
24.
go back to reference Hemminki K, Müller-Myhsok B, Lichtner P et al (2009) Low risk variants FGFR2, TNRC9 and LSP1 in German familial breast cancer patients. Int J Cancer. doi:10.1002/ijc.24986 Hemminki K, Müller-Myhsok B, Lichtner P et al (2009) Low risk variants FGFR2, TNRC9 and LSP1 in German familial breast cancer patients. Int J Cancer. doi:10.​1002/​ijc.​24986
25.
go back to reference Kawase T, Matsuo K, Suzuki T, Hiraki A, Watanabe M, Iwata H, Tanaka H, Tajima K (2009) FGFR2 intronic polymorphisms interact with reproductive risk factors of breast cancer: results of a case control study in Japan. Int J Cancer 125(8):1946–1952CrossRefPubMed Kawase T, Matsuo K, Suzuki T, Hiraki A, Watanabe M, Iwata H, Tanaka H, Tajima K (2009) FGFR2 intronic polymorphisms interact with reproductive risk factors of breast cancer: results of a case control study in Japan. Int J Cancer 125(8):1946–1952CrossRefPubMed
26.
go back to reference Liu M, Shan K, He Y et al (2009) The relationship between two FGFR2 polymorphisms and breast cancer. Zhongguo zhongliu linchuang 36(7):413–416 Liu M, Shan K, He Y et al (2009) The relationship between two FGFR2 polymorphisms and breast cancer. Zhongguo zhongliu linchuang 36(7):413–416
27.
go back to reference Prentice RL, Huang Y, Hinds DA, Peters U, Pettinger M, Cox DR, Beilharz E, Chlebowski RT, Rossouw JE, Caan B, Ballinger DG (2009) Variation in the FGFR2 gene and the effects of postmenopausal hormone therapy on invasive breast cancer. Cancer Epidemiol Biomarkers Prev 18(11):3079–3085CrossRefPubMed Prentice RL, Huang Y, Hinds DA, Peters U, Pettinger M, Cox DR, Beilharz E, Chlebowski RT, Rossouw JE, Caan B, Ballinger DG (2009) Variation in the FGFR2 gene and the effects of postmenopausal hormone therapy on invasive breast cancer. Cancer Epidemiol Biomarkers Prev 18(11):3079–3085CrossRefPubMed
28.
go back to reference Rebbeck TR, DeMichele A, Tran TV, Panossian S, Bunin GR, Troxel AB, Strom BL (2009) Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women. Carcinogenesis 30(2):269–274CrossRefPubMed Rebbeck TR, DeMichele A, Tran TV, Panossian S, Bunin GR, Troxel AB, Strom BL (2009) Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women. Carcinogenesis 30(2):269–274CrossRefPubMed
29.
go back to reference Samson M, Rama R, Swaminathan R, Sridevi V, Nancy KN, Rajkumar T (2009) CYP17 (T34C), CYP19 (Trp39Arg), and FGFR2 (C906T) polymorphisms and the risk of breast cancer in south Indian women. Asian Pac J Cancer Prev 10(1):111–114PubMed Samson M, Rama R, Swaminathan R, Sridevi V, Nancy KN, Rajkumar T (2009) CYP17 (T34C), CYP19 (Trp39Arg), and FGFR2 (C906T) polymorphisms and the risk of breast cancer in south Indian women. Asian Pac J Cancer Prev 10(1):111–114PubMed
30.
go back to reference Udler MS, Meyer KB, Pooley KA et al (2009) FGFR2 variants and breast cancer risk: fine-scale mapping using African American studies and analysis of chromatin conformation. Hum Mol Genet 18(9):1692–1703 Udler MS, Meyer KB, Pooley KA et al (2009) FGFR2 variants and breast cancer risk: fine-scale mapping using African American studies and analysis of chromatin conformation. Hum Mol Genet 18(9):1692–1703
31.
go back to reference Zheng W, Cai Q, Signorello LB, Long J, Hargreaves MK, Deming SL, Li G, Li C, Cui Y, Blot WJ (2009) Evaluation of 11 breast cancer susceptibility loci in African-American women. Cancer Epidemiol Biomarkers Prev 8(10):2761–2764CrossRef Zheng W, Cai Q, Signorello LB, Long J, Hargreaves MK, Deming SL, Li G, Li C, Cui Y, Blot WJ (2009) Evaluation of 11 breast cancer susceptibility loci in African-American women. Cancer Epidemiol Biomarkers Prev 8(10):2761–2764CrossRef
32.
go back to reference Tamimi RM, Lagiou P, Czene K, Liu J, Ekbom A, Hsieh CC, Adami HO, Trichopoulos D, Hall P (2010) Birth weight, breast cancer susceptibility loci, and breast cancer risk. Cancer Causes Control. doi:10.1007/s10552-009-9496-7 Tamimi RM, Lagiou P, Czene K, Liu J, Ekbom A, Hsieh CC, Adami HO, Trichopoulos D, Hall P (2010) Birth weight, breast cancer susceptibility loci, and breast cancer risk. Cancer Causes Control. doi:10.​1007/​s10552-009-9496-7
33.
go back to reference Carroll JS et al (2006) Genome-wide analysis of estrogen receptor binding sites. Nat Genet 38:1289–1297CrossRefPubMed Carroll JS et al (2006) Genome-wide analysis of estrogen receptor binding sites. Nat Genet 38:1289–1297CrossRefPubMed
34.
go back to reference Meyer KB, Maia A, O’Reilly M et al (2008) Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer. PLOS Biol 6:1098–1103CrossRef Meyer KB, Maia A, O’Reilly M et al (2008) Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer. PLOS Biol 6:1098–1103CrossRef
Metadata
Title
Quantitative assessment of the effect of FGFR2 gene polymorphism on the risk of breast cancer
Authors
Chenyou Jia
Yu Cai
Yushui Ma
Da Fu
Publication date
01-11-2010
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-0872-5

Other articles of this Issue 2/2010

Breast Cancer Research and Treatment 2/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine