BRCA2 N372H polymorphism and breast cancer susceptibility: a meta-analysis involving 44,903 subjects.

Published data on the association between BRCA2 N372H polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 22 studies including 22,515 cases and 22,388 controls were involved in this meta-analysis. Overall, no significant associations were found between BRCA2 N372H polymorphism and breast cancer risk when all studies pooled into the meta-analysis (NH versus NN: OR = 1.01, 95% CI = 0.97-1.05; HH versus NN: OR = 1.05, 95% CI = 0.97-1.13; dominant model: OR = 1.01, 95% CI = 0.98-1.05; and recessive model: OR = 1.05, 95% CI = 0.98-1.13). In the subgroup analysis by ethnicity, still no significant associations were found for Caucasians, Asians, or Africans. When stratified by study design, statistically significantly elevated risk was found for 372H allele based on population-based studies (HH versus NN: OR = 1.11, 95% CI = 1.01-1.21; dominant model: OR = 1.05, 95% CI = 1.00-1.10; recessive model: OR = 1.09, 95% CI = 1.00-1.18). In conclusion, this meta-analysis suggests that the BRCA2 372H allele may be a low-penetrant risk factor for developing breast cancer. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.