rs1219648

plus

Geno	Mag	Summary
(A;A)	0
(A;G)	2	1.20x risk for breast cancer
(G;G)	2.1	1.64x risk for breast cancer

Reference

GRCh38 38.1/142

Chromosome

10

Position

121586676

Gene

FGFR2

is a	snp
is	mentioned by
dbSNP	rs1219648
dbSNP (classic)	rs1219648
ClinGen	rs1219648
ebi	rs1219648
HLI	rs1219648
Exac	rs1219648
Gnomad	rs1219648
Varsome	rs1219648
LitVar	rs1219648
Map	rs1219648
PheGenI	rs1219648
Biobank	rs1219648
1000 genomes	rs1219648
hgdp	rs1219648
ensembl	rs1219648
geneview	rs1219648
scholar	rs1219648
google	rs1219648
pharmgkb	rs1219648
gwascentral	rs1219648
openSNP	rs1219648
23andMe	rs1219648
SNPshot	rs1219648
SNPdbe	rs1219648
MSV3d	rs1219648
GWAS Ctlg	rs1219648

GMAF

0.4008

Max Magnitude

2.1

?

(A;A) (A;G) (G;G)

28

Based on a study of ~2500 female patients of European ancestry with sporadic postmenopausal breast cancer, this SNP in the FGFR2 showed the greatest risk. The risk allele is rs1219648(G), with a pooled odds ratio of 1.64 (CI:1.42-1.90) for rs1219648(G;G) homozygotes, and an odds ratio of 1.20 (CI: 1.07-1.42) for rs1219648(A;G) heterozygotes, compared with rs1219648(A;A) homozygotes.[PMID 17529973 ]

rs1219648 represents the SNP in the FGFR2 gene with the strongest association with breast cancer. However, nearby SNPs are almost as predictive. In particular, the following SNP alleles all have linkage values of 0.96 or greater with the rs1219648(G) allele in European populations:

10.1371/journal.pbio.0060108 An experimental rationale is presented indicating that this SNP is part of a haplotype that increases risk for ER+ breast cancer by increasing FGFR2 transcription.

[PMID 18285324 ] rs1219648 is not associated with endometriosis risk.

[PMID 18483326 ] rs1219648 may account for a substantial fraction of breast cancer in Arab (12%), Ashkenazi (15%), and Sephardi Jewish (22%) populations.

[PMID 18845558] Based on a study of 1,049 Chinese breast cancer patients, carriers of risk alleles at three SNPs (rs2981582, rs1219648 and rs2420946) were at 1.36x increased risk for breast cancer (CI: 1.13-1.62, p = 0.001).

[PMID 18973230 ] A study of 1,173 Caucasian ovarian cancer patients did not find strong support for an association with rs1219648.

[PMID 19028704 ] A study of 1,225 Caucasian breast cancer patients found a significant association between rs1219648 but only in women with estrogen receptor positive (ER+), progesterone receptor positive (PR+) and HER2/Neu negative (HER2-) tumors. An interaction was also observed between combined hormone replacement therapy use and rs1219648 genotypes on breast cancer risk in Caucasian women (p = 0.010).

GWAS
SNP	rs1219648
PubMedID	[PMID 17529973 ]
Condition	Breast cancer
Gene	FGFR2
Risk Allele	G
pValue	1.00E-010
OR	1.2
95% CI	1.07-1.42

OMIM	114480
Desc	BREAST CANCER
Variant
Related	also

OMIM	176943
Desc	FIBROBLAST GROWTH FACTOR RECEPTOR 2; FGFR2
Variant
Related	also

[PMID 19789366 ] Evaluation of 11 breast cancer susceptibility loci in African-American women

[PMID 20640597] Risk of aggressive breast cancer in women of Han nationality carrying TGFB1 rs1982073 C allele and FGFR2 rs1219648 G allele in North China

[PMID 20699374 ] Evaluation of Breast Cancer Susceptibility Loci in Chinese Women

GWAS snp
PMID	[PMID 20872241]
Trait
Title	A combined analysis of genome-wide association studies in breast cancer
Risk Allele	G
P-val	2E-13
Odds Ratio	1.32 [1.22-1.42]

GWAS snp
PMID	[PMID 21263130]
Trait
Title	Novel Breast Cancer Susceptibility Locus at 9q31.2: Results of a Genome-Wide Association Study
Risk Allele
P-val	1E-30
Odds Ratio	1.3100 [1.25-1.37]

[PMID 21445572] Genetic polymorphisms and breast cancer risk: evidence from meta-analyses, pooled analyses, and genome-wide association studies

[PMID 21475998 ] Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States

[PMID 22087758 ] Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) study

[PMID 22303333 ] Replication of GWAS "Hits" by Race for Breast and Prostate Cancers in European Americans and African Americans

[PMID 21838531] Crosstalk between the FGFR2 and TP53 genes in breast cancer: data from an association study and epistatic interaction analysis

[PMID 18326623 ] Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33.

[PMID 18478591 ] Studies of genes in the FGF signaling pathway and oral clefts with or without dental anomalies.

[PMID 18535005 ] The search for genes contributing to endometriosis risk.

[PMID 18785201 ] Novel breast cancer risk alleles and endometrial cancer risk.

[PMID 19088016 ] Genetic susceptibility loci for breast cancer by estrogen receptor status.

[PMID 19094228 ] The influence of genetic variation in 30 selected genes on the clinical characteristics of early onset breast cancer.

[PMID 19219042 ] Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1.

[PMID 19497954 ] Histone-acetylated control of fibroblast growth factor receptor 2 intron 2 polymorphisms and isoform splicing in breast cancer.

[PMID 19500394 ] Genetic variants in FGFR2 and FGFR4 genes and skin cancer risk in the Nurses' Health Study.

[PMID 19639606 ] Correcting "winner's curse" in odds ratios from genomewide association findings for major complex human diseases.

[PMID 19738052 ] A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis.

[PMID 20085711 ] Leveraging genetic variability across populations for the identification of causal variants.

[PMID 20126254 ] Rare variants create synthetic genome-wide associations.

[PMID 20300826] Current evidence on the relationship between three polymorphisms in the FGFR2 gene and breast cancer risk: a meta-analysis.

[PMID 20364400] Quantitative assessment of the effect of FGFR2 gene polymorphism on the risk of breast cancer.

[PMID 20484103 ] Genetic and clinical predictors for breast cancer risk assessment and stratification among Chinese women.

[PMID 20554749 ] FGFR2 and other loci identified in genome-wide association studies are associated with breast cancer in African-American and younger women.

[PMID 20853316 ] FGFR2 intronic SNPs and breast cancer risk: associations with tumor characteristics and interactions with exogenous exposures and other known breast cancer risk factors.

[PMID 22144180] FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma.

[PMID 23073182] Breast cancer susceptibility associated with rs1219648 (fibroblast growth factor receptor 2) and postmenopausal hormone therapy use in a population-based United States study

[PMID 23435034 ] Breast cancer susceptibility associated with rs1219648 (fibroblast growth factor receptor 2) and postmenopausal hormone therapy use in a population-based United States study

[PMID 23225170] Genetic variants in FGFR2 and MAP3K1 are associated with the risk of familial and early-onset breast cancer in a South-American population

[PMID 24125968] An investigation of the effects of FGFR2 and B7-H4 polymorphisms in breast cancer

[PMID 24171766 ] Common low-penetrance risk variants associated with breast cancer in Polish women

[PMID 24454457 ] Case-control study on the fibroblast growth factor receptor 2 gene polymorphisms associated with breast cancer in chinese han women

[PMID 22910930 ] Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs: susceptibility and prognostic implications in Tunisians.

[PMID 22965832] Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population.

[PMID 23169889] Tooth agenesis association with self-reported family history of cancer.

[PMID 23184080] Assessing interactions between the associations of fibroblast growth factor receptor 2 common genetic variants and hormone receptor status with breast cancer risk.

[PMID 27572905] Genetic variants in FGFR2 and TNRC9 genes are associated with breast cancer risk in Pakistani women.

[PMID 29872343 ] Association of FGFR2 and PI3KCA genetic variants with the risk of breast cancer in a Chinese population.

[PMID 32366738] Low-penetrance susceptibility variants and postmenopausal oestrogen receptor positive breast cancer.

[PMID 33112566 ] The Associations of Common Genetic Susceptibility Variants with Breast Cancer in Jordanian Arabs: A Case-Control Study.