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Abstract：
BACKGROUND: The pathogenic/likely pathogenic (P/LP) variant detection rate and profile of PALB2, the third most important breast cancer gene, may vary between different populations.
METHODS: PALB2 was analyzed in peripheral blood samples of three independent cohorts: prospectively between September 2021 and March 2023 (i) in 1280 consecutive patients with breast and/or ovarian cancer (HBOC), (ii) in 568 patients with other cancers (controls), and retrospectively, (iii) in 191 young breast cancer (<33 years, yBC) patients. These data were compared with data of 134,187 non-cancer individuals retrieved from the Genome Aggregation Database.
RESULTS: Altogether, 235 cases (235/1280; 18.3%) carried at least one P/LP variant in one of the HBOC susceptibility genes. P/LP PALB2 variants were identified in 18 patients (1.4%; 18/1280) in the HBOC and 3 cases (1.5%; 3/191) in the yBC group. In the control group, only one patient had a disease-causing PALB2 variant (0.17%; 1/568) as a secondary finding not related to the disease, which was similar (0.15%; 205/134,187) in the non-cancer control group. The NM_024675.4:c.509_510delGA variant was the most common among our patients (33%; 6/18). We did not find a significant difference in the incidence of PALB2 disease-causing variants according to age; however, the median age of tumor onset was lower in PALB2 P/LP carriers versus wild-type patients (44 vs. 48 years). In our cohort, the odds ratio for breast cancer risk in women with PALB2 P/LP variants was between 8.1 and 9.3 compared to non-HBOC cancer patients and the non-cancer population, respectively.
CONCLUSIONS: PALB2 P/LP variants are not uncommon among breast and/or ovarian cancer patients. Their incidence was the same in the two breast cancer cohorts studied but may occur rarely in patients with non-breast/ovarian cancer. The c.509_510delGA variant is particularly common in the studied Hungarian patient population.
METHODS: PALB2 was analyzed in peripheral blood samples of three independent cohorts: prospectively between September 2021 and March 2023 (i) in 1280 consecutive patients with breast and/or ovarian cancer (HBOC), (ii) in 568 patients with other cancers (controls), and retrospectively, (iii) in 191 young breast cancer (<33 years, yBC) patients. These data were compared with data of 134,187 non-cancer individuals retrieved from the Genome Aggregation Database.
RESULTS: Altogether, 235 cases (235/1280; 18.3%) carried at least one P/LP variant in one of the HBOC susceptibility genes. P/LP PALB2 variants were identified in 18 patients (1.4%; 18/1280) in the HBOC and 3 cases (1.5%; 3/191) in the yBC group. In the control group, only one patient had a disease-causing PALB2 variant (0.17%; 1/568) as a secondary finding not related to the disease, which was similar (0.15%; 205/134,187) in the non-cancer control group. The NM_024675.4:c.509_510delGA variant was the most common among our patients (33%; 6/18). We did not find a significant difference in the incidence of PALB2 disease-causing variants according to age; however, the median age of tumor onset was lower in PALB2 P/LP carriers versus wild-type patients (44 vs. 48 years). In our cohort, the odds ratio for breast cancer risk in women with PALB2 P/LP variants was between 8.1 and 9.3 compared to non-HBOC cancer patients and the non-cancer population, respectively.
CONCLUSIONS: PALB2 P/LP variants are not uncommon among breast and/or ovarian cancer patients. Their incidence was the same in the two breast cancer cohorts studied but may occur rarely in patients with non-breast/ovarian cancer. The c.509_510delGA variant is particularly common in the studied Hungarian patient population.
摘要：
背景：第三重要的乳腺癌基因PALB2的致病性/可能致病性（P/LP）变异检出率和概况，不同人群之间可能有所不同。
方法：在三个独立队列的外周血样本中分析了PALB2：在2021年9月至2023年3月（i）的1280例连续乳腺癌和/或卵巢癌（HBOC）患者中，（ii）在568例其他癌症患者（对照）中，回顾性地，（iii）在191例年轻乳腺癌（<33岁，yBC)患者。将这些数据与从基因组聚集数据库检索的134,187名非癌症个体的数据进行比较。
结果：总之，235例（235/1280；18.3％）在HBOC易感基因之一中携带至少一个P/LP变体。在HBOC组中有18例患者（1.4％;18/1280）和yBC组中有3例患者（1.5％;3/191）中发现了P/LPPALB2变体。在对照组中，只有一名患者有一个致病的PALB2变异（0.17％;1/568）作为与疾病无关的次要发现，与非癌症对照组相似（0.15％；205/134,187）。NM_024675.4：c.509_510delGA变体在我们的患者中最常见（33％；6/18）。根据年龄，我们没有发现PALB2致病变异的发生率有显著差异；然而，与野生型患者相比，PALB2P/LP携带者的中位肿瘤发病年龄较低(44vs.48年）。在我们的队列中，与非HBOC癌症患者和非癌症人群相比，PALB2P/LP变异女性的乳腺癌风险比值比为8.1至9.3，分别。
结论：PALB2P/LP变异体在乳腺癌和/或卵巢癌患者中并不少见。在所研究的两个乳腺癌队列中，它们的发病率相同，但在非乳腺癌/卵巢癌患者中很少发生。c.509_510delGA变体在所研究的匈牙利患者群体中特别常见。
方法：在三个独立队列的外周血样本中分析了PALB2：在2021年9月至2023年3月（i）的1280例连续乳腺癌和/或卵巢癌（HBOC）患者中，（ii）在568例其他癌症患者（对照）中，回顾性地，（iii）在191例年轻乳腺癌（<33岁，yBC)患者。将这些数据与从基因组聚集数据库检索的134,187名非癌症个体的数据进行比较。
结果：总之，235例（235/1280；18.3％）在HBOC易感基因之一中携带至少一个P/LP变体。在HBOC组中有18例患者（1.4％;18/1280）和yBC组中有3例患者（1.5％;3/191）中发现了P/LPPALB2变体。在对照组中，只有一名患者有一个致病的PALB2变异（0.17％;1/568）作为与疾病无关的次要发现，与非癌症对照组相似（0.15％；205/134,187）。NM_024675.4：c.509_510delGA变体在我们的患者中最常见（33％；6/18）。根据年龄，我们没有发现PALB2致病变异的发生率有显著差异；然而，与野生型患者相比，PALB2P/LP携带者的中位肿瘤发病年龄较低(44vs.48年）。在我们的队列中，与非HBOC癌症患者和非癌症人群相比，PALB2P/LP变异女性的乳腺癌风险比值比为8.1至9.3，分别。
结论：PALB2P/LP变异体在乳腺癌和/或卵巢癌患者中并不少见。在所研究的两个乳腺癌队列中，它们的发病率相同，但在非乳腺癌/卵巢癌患者中很少发生。c.509_510delGA变体在所研究的匈牙利患者群体中特别常见。
