In this paper we used BRCA1 and BRCA2 sequence data from Australian breast cancer cases less than 40 years of age at the time of diagnosis to classify individuals according to their deleterious mutation status, and resolved haplotypes of common polymorphisms separately in the groups that did and did not carry deleterious mutations.
We found weak evidence that one haplotype of BRCA1 variants is over-represented in carriers of deleterious mutations. This haplotype contains the minor allele for 3232A > G variant which we found to be over-represented among deleterious mutation carriers. Other haplotypes containing the minor allele "G" also occurred more frequently in deleterious mutation group.
In BRCA2 we found evidence that the population frequency of the most common haplotype in individuals carrying deleterious mutations was greater than 95%, when the corresponding frequency in those without deleterious mutations was only 65%. Individuals without this haplotype are unlikely to carry deleterious mutations but the predictive power of this haplotype for deleterious mutations is low since it occurs very frequently in those with no deleterious mutations (namely the vast majority of the population).
The sample size of the deleterious mutation group was small for both genes, with only 13 and 11 individuals carrying deleterious mutations for BRCA1 and BRCA2 respectively. The power to detect differences in haplotype frequencies is therefore quite low, which might explain some of the high p-values obtained from permutation testing.
Our selection of tagSNPs for BRCA1 gene has one in common with tagSNPs selection of Osorio et al.  (where they have used 4427T- > C as a tagSNP) and Cox et al.  (Q356R as a tagSNP). In Osorio et al. their class II haplotype occurs more frequently among BRCA1 mutation carriers. This haplotype is essentially characterized by the 4427C- > T variant allele which was used as a tagSNP in our study. We found that minor allele occurred more frequently in deleterious mutation carriers compared to non-carriers (32% vs 23%) but the evidence for this at the population level was weak p = 0.25. Cox et al. found slight increase in risk of breast cancer with the Q356R polymorphism, contradicting an earlier result showing an inverse association . We found that Q356R occurred more frequently among deleterious mutation carriers but again the evidence at the population level was weak.
There have been several case control studies seeking BRCA1 and BRCA2 variants associated with an increased risk of breast cancer. Freedman at al.  investigated if common BRCA2 variants contribute to the more common forms of breast cancer in a large multiethnic cohort. Twenty one tagging SNPs were selected to predict common BRCA2 haplotypes. A number of haplotypes were found to be associated with increased risk of breast cancer, all of which could be attributed to a single marker (intron 24: rs206340) that was not selected as a tag SNP for analysis in our study. Freedman at al.  repeated similar analysis on BRCA1 gene. Specifically, they have used 28 variants to define patterns of common variation (5 in common with variants used in our study: Q356R, P871L, K1183R, S1613G and E1038G). They found no evidence for significant association between common variation in BRCA1 and risk of breast cancer.
The suggestive associations that we have observed do not imply a physical association on the same chromosome (as would be the case if the rare, deleterious mutation was in cis phase with a haplotype consisting of, for example, the minor alleles of several common variants) or a functional association (as might be the case even if the rare, deleterious mutation was in trans phase with a common variant haplotype, since it may still act to modify the penetrance of the disease causing variant). Establishing the phase of rare, deleterious mutations and the common variants we used to define haplotypes for both BRCA1 and BRCA2 would require either a much larger sample size than was available for this study, genetic data from extended pedigrees or expensive laboratory investigation.