RAD51 135G>C substitution increases breast cancer risk in an ethnic-specific manner: a meta-analysis on 21236 cases and 19407 controls

RAD51 is a homolog of bacterial RecA protein, which plays an important role in preserving stability of the genome. RAD51 interacts with BRCA1 and BRCA2 for homologous recombination repair. A functional polymorphism (135G > C) in the RAD51 gene has been a subject of great interest, which is evidenced by at least 28 case-control studies and eight meta-analyses undertaken on this polymorphism till now. We undertook a meta-analysis on RAD51 135G > C data for 21236 cases and 19407 controls pooled from 28 studies on breast cancer in women. Pooled data analysis suggested a significant association of the substitution with breast cancer in the recessive model (GG + GC versus CC) and in the co-dominant models comparing GG versus CC and GC versus CC. Analysis of the results suggested that ‘CC’ genotype is a significant breast cancer risk factor in comparison to ‘GG’ and ‘GC’ genotypes. We also undertook pooled analyses on different ethnic groups and found that ‘CC’ was a strong risk factor in Caucasians, but not in East-Asians and populations of mixed ethnicity. In conclusion, the RAD51 135G > C substitution in the homozygous form (CC) increases the risk of breast cancer in an ethnic-specific manner.