presents the descriptive characteristics of the study sample. The allele frequencies for each locus were similar to those previously reported in EA populations (1
) and are comparable with those found in public databases for AA populations. All variants were consistent with Hardy–Weinberg proportions in controls of both races. Tumor marker characteristics differed as expected between AA and EA, with AA having a lower proportion of ER+, PR+ and HER2+ tumors.
Descriptive characteristics of 584 AA and 1225 EA participants in the Women’s Insights and Shared Experiences study
Consistent with previous reports, we observed a significant association between FGFR2
genotypes and breast cancer in EA post-menopausal women (), with per-allele effects of 1.23 (95% CI: 1.03–1.46) for rs1219648 and 1.26 (95% CI: 1.04–1.53) for rs2981582. We also report that the effect of these genotypes appears to be limited to ER+ tumors, PR+ tumors and HER2− tumors. In every case, the per-allele effects of FGFR2
ranged from 1.30 to 1.43. In ER−, PR− or HER2+ tumors, per-allele effects were very near OR
1.0. We did not observe a significant association with MAP3K1
in EA post-menopausal women.
Adjusted ORs with 95% CIsa for the effect of genotypes on breast cancers: 1225 EA women
In contrast to the results in EA post-menopausal women, we observed no effect of FGFR2
in AA post-menopausal women (). None of the per-allele OR effects for the two FGFR2
SNPs was >1.2, and many of the estimates were OR <1.0. For MAP3K1
, we observed no significant association overall. However, we report statistically significant associations of MAP3K1
rs889312 genotypes in ER+, PR+ or HER2− tumors (). In each case, the per-allele OR effect was approximately OR
1.5, with homozygote CC genotype effects in the range of ~2.4–2.8.
Adjusted ORs with 95% CIsa for the effect of genotypes on breast cancers: 584 AA women
We also considered the joint effects of FGFR2
genotypes and hormone-related breast cancer risk factors ( and ). FGFR2
rs1219648 genotypes interacted significantly with the use of CHRT (P
0.010). Breast cancer risk was elevated among never users of CHRT who carried any FGFR2
rs1219648 genotype or if they had used CHRT but carried the AA genotype. For FGFR2
rs2981582, we also observed a significant increase in breast cancer risk among women who had never used CHRT and had the rs2981582 TT genotype (OR
1.87, 95% CI: 1.08–3.22). Nulliparous women with the FGFR2
rs1219648 GG genotype were at significantly increased breast cancer risk (OR
4.04, 95% CI: 1.26–12.98), whereas no excess risk was observed for any other genotype- or parity-specific group. Risk was also increased among nulliparous women with the rs2981582 TT genotype (OR
9.68, 95% CI: 1.90–49.31).
Adjusted ORs with 95% CIsa for the effect of genotypes on breast cancers in 1225 EA women by hormonal exposures
Adjusted ORs with 95% CIsa for the effect of genotypes on breast cancers in 584 AA women by hormonal exposures
No statistically significant interactions were observed among AA women (). However, we observed two stratum-specific effects. First, we report an inverse relationship with breast cancer risk among women who carried the MAP3K1
AA genotype and who had a later age at menarche (OR
0.44, 95% CI: 0.21–0.93). Second, we report an inverse relationship between women who carried the FGFR2
rs1219648 AA genotype and were parous (OR
0.31, 95% CI: 0.10–0.94).
Finally, because these two genes are both involved in the MAPK signal transduction pathway, we evaluated the potential for gene–gene interaction effects. Among EA women, we observed no statistically significant interactions for carriage of any variant for MAP3K1
rs889312 and either FGFR2
rs1219648 or rs2981582 (P
-value for interaction: 0.376 and 0.569, respectively). In AA women, we found no statistically significant interactions for carriage of any variant for MAP3K1
rs889312 and FGFR2
-value for interaction: 0.464). However, we did observe a significant interaction between MAP3K1
rs889312 and FGFR2
-value for interaction: 0.022). Specifically, we observed that the highest risk group was in AA women who carried any MAPK31 AC or CC genotypes and the FGFR2
rs2981582 CC genotype (OR
3.84, 95% CI: 1.83–8.04). This interaction is consistent with the main effects for each of these genotypes shown in .