Despite progress in diagnostic modalities, gastric cancer (GC) is still a challenge for medicine. On a global scale more than 700,000 people die each year of GC [
1].
Helicobacter pylori is a Class 1 carcinogen that is consistently considered a major risk factor associated with GC, but it is still not clear why most infected individuals never develop this malignancy. Therefore, a genetic predisposition has been postulated and approximately 5 % of the total GC burden is associated with hereditary germline mutations in genes causing a highly penetrant, autosomal dominant predisposition [
2]. One of the few known mutations that predisposes to the development of diffuse gastric cancer in young patients is the
CDH1 gene mutation [
3,
4]. However, a study has shown that the
CDH1 gene mutation is not present among Polish families that meet hereditary diffuse gastric cancer (HDGC) criteria [
5]. Recently, it has been shown that founder mutations in
CHEK2 gene are associated with increased GC risk in Polish patients. However, the observed risk was low (OR = 1.6, p = 0.004) and concerned only 8.7 % of 658 patients with gastric cancer unmatched for age or family history [
6]. The role of other genes, in particular tumor suppressor genes that help repair damaged DNA and ensure the stability of cellular genetic material, is not clear. Although germline mutations in the tumor suppressor
BRCA1 and
BRCA2 genes are associated with a high risk of breast and ovarian cancer, however, they have also been shown to correlate with other cancers, including gastric cancer. There are several studies which investigated the role of
BRCA1/2 gene in gastric cancer in different populations. In a single Israeli study, selected
BRCA2 mutations were found in 5.7 % of 35 GC patients [
7]. Other reports are mainly indirect and family-based studies, in which a risk of gastric cancer was analyzed on the basis of the observed and expected number or incidence of GC in
BRCA1/2 mutation carriers or their relatives [
8‐
13]. Friedenson [
14] has summarized these reports, analyzing data from more than 30 epidemiological studies on the incidence of other than the breast or ovarian cancers in
BRCA1 and
BRCA2 mutation carriers and in large populations eligible for mutation testing. He estimated an elevated risk for stomach cancer with RR = 1.69 (1.21-2.38) as well as other cancers including the pancreas, colon and prostate cancer. The majority of published analyses on the correlation between
BRCA1 and
BRCA2 mutations and GC are indirect and based on the observation of GC incidence in families with detected mutation, but do not show the prevalence of
BRCA1/2 mutations in patients with diagnosed gastric cancer. The distribution of
BRCA1 and
BRCA2 mutations in European populations is varied and is characterized by the genetic homogeneity or heterogeneity of a particular population [
15]. Górski et al. [
16] in a study of 66 familial breast/ovarian cancer patients reported 35 families with detected mutations, including 29 (82.9 %) being three founder mutations of
BRCA1 (C61G, 4153delA, 5382insC). Other studies confirmed statistically significant high contribution of three founder
BRCA1 mutations in Polish breast/ovarian cancer patients [
17‐
21]. The contribution of these mutations was also investigated in other cancers. Cybulski et al. [
22] analyzed
BRCA1 mutations (C61G, 4153delA, 5382insC) in a large group of 1793 patients with prostate cancer and 4570 population controls and found an association of C61G, 4153delA but not 5382insC with an increased prostate cancer risk (OR = 3.6, p = 0.045). In another Polish study, three
BRCA1 founder mutations were analyzed in a group of 2,398 colorectal cancer patients, but they were not associated with the overall cancer risk [
23]. However, they were found to correlate with family history and younger age at diagnosis. Apart from founder mutations in Polish cancer patients, several other recurrent
BRCA1 (185delAG, 3819del5, 3875del4, 5370C > T) and
BRCA2 (886delGT, 4075delGT, 5467insT, 6174delT, 8138del5) mutations were detected [
17‐
21,
24].