加拿大弥漫性胃癌患者队列中的种系变体和表型谱。
Germline variants and phenotypic spectrum in a Canadian cohort of individuals with diffuse gastric cancer.
机构信息
Sinai Health System, Zane Cohen Centre for Digestive Diseases, University of Toronto, Toronto, ON.
Sinai Health System, Department of Surgery, University of Toronto, Toronto, ON.
出版信息
Curr Oncol. 2020 Apr;27(2):e182-e190. doi: 10.3747/co.27.5663. Epub 2020 May 1.
BACKGROUND
pathogenic variants (pvs) cause most cases of inherited diffuse gastric cancer (dgc), but have low detection rates and vary geographically. In the present study, we examined hereditary causes of dgc in patients in Ontario.
METHODS
testing through single-site or multi-gene panels was conducted for patients with dgc meeting the 2015 International Gastric Cancer Linkage Consortium (igclc) criteria, or with isolated dgc at less than 50 years of age, or with a strong family history of cancer identified at the Zane Cohen Centre (zcc). All positive patients at zcc, regardless of cancer history, were summarized.
RESULTS
In 15 of 85 patients with dgc (17.6%), a pv or likely pv was identified through single-site ( = 43) or multi-gene panel ( = 42) testing. The detection rate was 9.4% overall (8 of 85) and 11% using igclc criteria (7 of 65). No pvs were identified in patients with isolated dgc at less than 40 years of age, but 1 pv was identified in a patient with isolated dgc at less than 50 years of age. Multi-gene panels identified 9 pvs (21.4%), including , , and . Review of 81 carriers identified 10% with dgc (median age: 48 years; range: 38-59 years); 41% were unaffected (median age: 53 years; range: 26-89 years). Observed malignancies other than dgc or lobular breast cancer (lbc) included colorectal, gynecologic, kidney or bladder, prostate, testicular, and ductal breast cancers. Lobular-breast cancer was seen only in 3 families.
CONCLUSIONS
In Ontario, the detection rate of pvs in patients with dgc was low: no pvs were identified in patients with isolated dgc at less than 40 years of age, and 1 was identified in a patient with isolated dgc at less than 50 years of age. Isolated lbc with no dgc was observed in positive families, as were pathology-confirmed nondgc or non-lbc malignancies, which had not previously been reported. Given a phenotype that overlaps with other hereditary conditions, multi-gene panels are recommended for all patients with dgc at less than 50 years of age and for those meeting igclc criteria.
背景
致病性变异（pvs）导致大多数遗传性弥漫性胃癌（dgc）病例，但检测率较低且存在地域差异。本研究中，我们检测了安大略省 dgc 患者的遗传病因。
方法
对符合 2015 年国际胃癌连锁研究联盟（igclc）标准的 dgc 患者，或年龄小于 50 岁的孤立性 dgc 患者，或在 Zane Cohen 中心（zcc）确定有强烈家族癌症史的患者进行单基因或多基因panel 检测。对所有 zcc 的阳性患者，无论癌症病史如何，均进行了总结。
结果
在 85 例 dgc 患者中（17.6%），通过单基因（n=43）或多基因panel（n=42）检测，发现了 1 例或疑似 pv。总体检出率为 9.4%（8/85），符合 igclc 标准的检出率为 11%（7/65）。年龄小于 40 岁的孤立性 dgc 患者中未发现 pvs，但年龄小于 50 岁的孤立性 dgc 患者中发现 1 例 pvs。多基因panel 检测出 9 例 pvs（21.4%），包括、和。对 81 例携带者的分析显示，有 10%患有 dgc（中位年龄：48 岁；范围：38-59 岁）；41%无影响（中位年龄：53 岁；范围：26-89 岁）。除 dgc 或小叶乳腺癌（lbc）外，观察到的其他恶性肿瘤包括结直肠癌、妇科肿瘤、肾或膀胱癌、前列腺癌、睾丸癌和导管乳腺癌。仅在 3 个家族中发现了小叶乳腺癌。
结论
在安大略省，dgc 患者 pvs 的检出率较低：年龄小于 40 岁的孤立性 dgc 患者中未发现 pvs，年龄小于 50 岁的孤立性 dgc 患者中发现 1 例。在阳性家族中观察到了无 dgc 的孤立性 lbc，以及此前未报道的经病理证实的非 dgc 或非 lbc 恶性肿瘤。鉴于与其他遗传性疾病有重叠的表型，建议所有年龄小于 50 岁的 dgc 患者和符合 igclc 标准的患者进行多基因panel 检测。
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