Rs1219648

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:

• rs2981579(A)
• rs2420946(T)
• rs11200014(A)

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

[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