Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1, 995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction

<症例>十二指腸原発の悪性リンパ腫と早期胃癌を合併した一例

We report here a 65-year old man with primary duodenal malignant lymphoma combined with gastric lymphoma and early gastric cancer. Malignant lymphoma in the bulbus of the duodenum was suspected of by endoscopic biopsy during follow up of duodenal ulcer. Preoperative examination revealed an extension of malignant lymphoma from the bulbus to the stomach in combination with early gastric cancer. We perfomed a pancreaticoduodenectomy because the tumor invaded to the second portion of the duodenum. The postoperative course was uneventful and he received adjuvant chemotherapy following surgery. To our knowledge, this case is the first report of primary duodenal malignant lymphoma combined with gastric lymphoma and early gastric cancer.消化管原発の悪性リンパ腫のうち十二指腸原発悪性リンパ腫は, 比較的稀である. 早期胃癌を併発した症例は更に少なく, 本邦では文献上二例目である. 今回, 我々は更に胃リンパ腫も合併した非常に稀な症例を経験したのでここに報告する. 症例は65歳の男性. 主訴は上腹部痛. 現病歴は, 三年前に十二指腸潰瘍 stage A1 と診断されその後内視鏡にて経過観察していたが, 今回十二指腸球部に異常を認め, 更に生検にて悪性リンパ腫が疑われたので当科を紹介された. 術前検査にて病巣は, 十二指腸球部を中心に胃粘膜下に浸潤しており, さらに早期胃癌の合併が疑われ開腹, 弊膵十二指腸切除術にて上記が確認された. 今回術前の生検で胃悪性リンパ腫は偽陰性であったが, EUS では悪性リンパ腫に典型的な所見を呈した部位が有り, 病巣の診断に EUS が有効であった. また予後については治癒切除し得たが, Contreary の分類では CLASS III に相当するため術後に化学療法(VEMP療法)を施行した

Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer‐Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1,995). Eleven breast cancer susceptibility genes were analyzed using target‐capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third‐degree relatives), triple‐negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69‐0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high‐risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction