BMC Cancer 2004, 4 http://www.biomedcentral.com/1471-2407/4/9 KaFmingo-ucnrogehfoe2mrtablereraesltatcivaensceorf cpurmobualantdivse risk estimates up to age 80 for more frequent single nucleotide polymorphic variants Kin-cohort breast cancer cumulative risk estimates up to age 80 for more frequent single nucleotide polymorphic variants among female relatives of probands. (Amino acids and their symbols: D: Aspartic Acid, E: Glutamic acid, R: Arginine, H: Histi- dine, Q: Glutamine, N: Asparagine, P: Proline, S: Serine.) breast cancer risk. Additional information, both func- tional and genotypic, is worth pursuing for the APEX 148 variant. POLD1 (polymerase δ) participates in a possibly redundant sub-pathway within the base excision repair "long patch" process [reviewed in [33]]. This particular variant has not been as well characterized in regard to can- cer risk, compared to other SNPs in base excision repair genes, but observed RRs in our study were around two- fold up to ages 50 and 70 such that this SNP deserves fur- ther study to confirm or refute its role in breast cancer risk. We evaluated six SNPs recently characterized in the BRCA1-interacting genes ZNF350 (ZBRK1) and BRIP1 (BACH1) [34]. Among those, the nonconservative BRIP1 P919S substitution showed a strong association with 4.5- fold and 6.9-fold (for PS and PP vs. SS, respectively) increased risks of breast cancer up to age 50. However, the association was markedly attenuated when observation was extended to age 70. This could be a chance finding, or, the variant may be associated predominantly with risk of pre-menopausal breast cancer. Further evaluation of this SNP in other study populations will be required. Two growth factor genes, IGFBP3 and TGFß1, were evalu- ated because of their roles in controlling cellular growth and changes associated with malignant progression. Pre- vious reports suggested an association between the - 202A>C IGFBP3 SNP and risk of pre-menopausal breast cancer, primarily through its effect on circulating IGFBP3 levels [35] and/or IGF-1 levels [36]. Although we did not Page 7 of 12 (page number not for citation purposes)