Gastric Cancer in Portuguese Families with BRCA2 Gene Mutations

ABSTRACT Background and objective BRCA 1/2 are tumor suppressor genes responsible for a high number of hereditary breast and ovarian cancers. BRCA 2 mutations are also associated with higher risk of other cancers: prostate, melanoma, pancreatic, gastric and bile duct cancer. BRCA2 mutations are more frequent than BRCA1 mutations in Portugal and GC has, historically, a high incidence in this country. Our objective was to analyze the frequency and characteristics of GC in confirmed BRCA2 Portuguese families. Methods Retrospective analysis of all BRCA2 families registered in our Clinic. All cases of GC, on the mutated side of the family, for 3 consecutive generations, were registered. The control group consisted of breast cancer families with standard risk of breast cancer (FSRBC) (with probability Results Of 119 families with BRCA 2 mutation analyzed, 35 families (29.4%) had reported cases of GC. Of these 35 families, 24 had one case of GC, 10 had two cases and one family had seven cases. A total of 51 GC cases were found: 20 females (39%) and 31 males (61%) with a median age at diagnosis of 60 years (28–80 yrs). Pathological confirmation was available in 5 cases (4 adenocarcinoma, 1 neuroendocrine). Two cases of GC were diagnosed in BRCA2 pts who were breast cancer survivors and 1 in a healthy woman previously submitted to prophylactic adnexectomy. These 35 families had 19 different BRCA2 mutations, 15 C.156_157insAlu (Portuguese founder mutation). No difference between the frequency of GC in families with C.156_157insAlu mutation and in other BRCA2 families was observed. In the control group of 163 families, only 19 (12%) had cases of GC (1 case in 18 families and 2 cases in 1 family). The median age was 61 years (range 52–76). The frequency of GC in BRCA 2 families was higher compared with the frequency in FSRBC, odds ratio 3.0 CI (1.7–5.3), p  Conclusion(s) BRCA2 mutations are associated with a higher risk of GC compared with FSRBC. The Portuguese founder mutation was not associated with higher prevalence of GC compared to the other BRCA 2 mutations. Since GC has already a high incidence in our country, we believe this data supports the need for GC screening in BRCA2 pts. Disclosure All authors have declared no conflicts of interest.