Polymorphisms in Second Intron of the FGFR2 Gene Are Associated with the Risk of Early-Onset Breast Cancer in Chinese Han Women

Fu, Fangmeng; Huang, Meng; Song, Chuan-Gui; Lin, Shu‐Fang; Huang, Heguang

doi:10.1620/tjem.226.221

Cited by 21 publications

(13 citation statements)

References 36 publications

(40 reference statements)

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“…However, limited researches have been done on the impact of rs1219648 on early onset breast cancer. Although the recent study by Chun-Lian Liu and coworkers has been refused the impact of rs1219648 in premenopausal breast cancer (Liu et al, 2013), in another investigation carried out on Chines Han woman a great association appeared between rs1219648 and premenopausal breast cancer (Fu et al, 2012). In our study the association between the G allele of rs1219648 FGFR2 and early onset breast cancer is in agreement with the aforementioned study (p=0.006).…”

Section: Discussionsupporting

confidence: 91%

“…Five single nucleotide polymorphisms (SNP) of FGFR2 gene are associated with breast cancer (Katoh, 2008 other SNPs, the role of rs1219648 (IVS2±7033A>G) in postmenopausal breast cancer is more remarkable (Hunter et al, 2007;Zhang et al, 2010a). Despite this clear evidence some researches stress on the effect of this polymorphism on premenopausal breast cancer (Fu et al, 2012). Genetic alterations of FGFR2 cause aberrant activation of FGFR2 signaling in breast cancer (Katoh, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population

Saadatian¹,

Gharesouran²,

Ghojazadeh³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Breast cancer is the most common cancer among women in the world. In Iran, the incidence of breast cancer is on the increase. We here studied the association of rs1219648 in FGFR2 and rs1042522 in TP53 and their interaction in development of early onset sporadic breast cancer in Iranian Azeri population to evaluate epistatic effects on the risk of mammary neoplasia. We genotyped the two polymorphisms in 100 women with early onset breast cancer and 100 healthy women by PCR-RFLP. Allele frequency differences were tested using chi 2 -test with 95% confident intervals. Our results indicated a statistically significant association (p<0.05) between rs1219648, but not rs1042522, and risk of breast cancer. We also found that the combination of FGFR2 major genotype and TP53 hetero genotype had protective effects against breast cancer , while the hetero allele of FGFR2 in combination with the minor genotype of TP53 was associated with a high risk. This study revealed an important crosstalk between two polymorphisms in FGFR2 and TP53 in development of breast cancer. These candidates risk variants should be further evaluated in studies with a larger sample size.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population

Saadatian¹,

Gharesouran²,

Ghojazadeh³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…In this case-control study of BC in Pakistani women, significant associations were observed between two SNPs of FGFR2 [rs1219648: P=9.08e-006 (GG, P=0.000087, AG, P=0.000018) and rs2981582: P= 0.005 (CT, P= 0.001, TT, P= 0.097)]. These results are consistent with results obtained from other Asian regions, including China (16,32,37), Japan (38) and India (18). Furthermore, the SNPs rs1219648 and rs2981582 of FGFR2 have been consistently associated with BC risk in several other ethnic groups, including European (39), Hispanic and non-Hispanic Caucasian women from Southwestern United States (40), African American (29,41) and Tunisian (42) women populations.…”

Section: Discussionsupporting

confidence: 89%

“…However, similar SNPs do not show any association with the risk of BC in women of African ancestry (29)(30)(31). Taken together, the novel genetic variants of the genes FGFR2, MAP3K1 and TNRC9 have shown a marked association with BC in populations of diverse ethnicity (32), and the variants identified as BC risk factors have revealed a variable impact on the risk of BC associated with different populations. Hence, the replications of previously BC associated loci in multiple populations are required to explore the genetic heterogeneity of BC (18).…”

Section: Introductionmentioning

confidence: 90%

Genetic variants in FGFR2 and TNRC9 genes are associated with breast cancer risk in Pakistani women

Mazhar

Jamil

Bashir

et al. 2016

Molecular Medicine Reports

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Single nucleotide polymorphisms (SNPs) lead to genetic differences in breast cancer (BC) susceptibility among women from different ethnicities. The present study aimed at investigating the involvement of SNPs of three genes, including fibroblast growth factor receptor 2 (FGFR2), trinucleotide-repeat-containing 9 (TNRC9) and mitogen-activated protein kinase kinase kinase 1 (MAP3K1), as risk factors for the development of BC. A case‑control study (90‑100 cases; 90‑100 controls) was performed to evaluate five genetic variants of three genes, including FGFR2 (SNPs: rs1219648, rs2981582), TNRC9 (SNPs: rs8051542, rs3803662) and MAP3K1 (SNP: rs889312) as BC risk factors in Pakistani women. Significant associations were observed between BC risk and two SNPs of FGFR2 [rs2981582 (P=0.005), rs1219648 (P=9.08e‑006)] and one SNP of TNRC9 [rs3803662) (P=0.012)] in Pakistani women. On examining the different interactions of these SNPs with various clinicopathological characteristics, all three associated genetic variants, rs2981582 rs1219648 and rs3803662, exhibited a greater predisposition to sporadic, in comparison to familial, BC. Furthermore, there was an increased effect of BC risk between haplotype combinations of the two SNPs of FGFR2 (rs2981582 and rs1219648) in Pakistani women. The results of the present study suggest that variants of FGFR2 and TNRC9 may contribute to the genetic susceptibility of BC in Pakistani women.

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“…Ahsan et al [1], for example, reported genome-wide significant p-values for 4 FGFR2 SNPs and young-onset breast cancer, with the smallest p-value seen for rs2981579. Other studies have also observed associations between FGFR2 SNPs and young-onset breast cancer [41, 42, 69, 74]. …”

Section: Methodsmentioning

confidence: 92%

Previous GWAS hits in relation to young-onset breast cancer

Shi

O’Brien

Sandler

et al. 2016

Breast Cancer Res Treat

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Purpose Genome-wide association studies (GWAS) have identified dozens of single nucleotide polymorphisms (SNPs) associated with breast cancer. Few studies focused on young-onset breast cancer, which exhibits etiologic and tumor-type differences from older-onset disease. Possible confounding by prenatal effects of the maternal genome has also not been considered. Methods Using a family-based design for breast cancer before age 50, we assessed the relationship between breast cancer and 77 GWAS-identified breast cancer risk SNPs. We estimated relative risks (RR) for inherited and maternally-mediated genetic effects. We also used published RR estimates to calculate genetic risk scores and model joint effects. Results Seventeen of the candidate SNPs were nominally associated with young-onset breast cancer in our 1,296 non-Hispanic white affected families (uncorrected p-value<0.05). Top-ranked SNPs included rs3803662-A (TOX3, RR=1.39; p=7.0×10−6), rs12662670-G (ESR1, RR=1.56; p=5.7×10−4), rs2981579-A (FGFR2, RR=1.24; p=0.002), and rs999737-G (RAD51B, RR=1.37; p=0.003). No maternally-mediated effects were found. A risk score based on all 77 SNPs indicated that their overall relationship to young-onset breast cancer risk was more than additive (additive-fit p=2.2×10−7) and consistent with a multiplicative joint effect (multiplicative-fit p=0.27). With the multiplicative formulation, the case sister’s genetic risk score exceeded that of her unaffected sister in 59% of families. Conclusions The results of this family-based study indicate that no effects of previously-identified risk SNPs were explained by prenatal effects of maternal variants. Many of the known breast cancer risk variants were associated with young-onset breast cancer, with evidence that TOX3, ESR1, FGFR2, and RAD51B are important for young-onset disease.

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Polymorphisms in Second Intron of the FGFR2 Gene Are Associated with the Risk of Early-Onset Breast Cancer in Chinese Han Women

Cited by 21 publications

References 36 publications

Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population

Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population

Genetic variants in FGFR2 and TNRC9 genes are associated with breast cancer risk in Pakistani women

Previous GWAS hits in relation to young-onset breast cancer

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