K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Cancer Med. 2023 Mar;12(6):6659-6667. doi: 10.1002/cam4.5448. Epub 2022 Nov 16.
A common 30 kb deletion affecting the APOBEC3A and APOBEC3B genes has been linked to increased APOBEC activity and APOBEC-related mutational signatures in human cancers. The role of this deletion as a cancer risk factor remains controversial.
We genotyped the APOBEC3A/B deletion in a sample of 1,470 Norwegian endometrial cancer cases and compared to 1,918 healthy controls. For assessment across Caucasian populations, we mined genotypes of the SNP rs12628403, which is in strong linkage disequilibrium with the deletion, in a GWAS dataset of 4,274 cases and 18,125 healthy controls, through the ECAC consortium.
We found the APOBEC3A/B deletion variant to be significantly associated with reduced risk of endometrial cancer among Norwegian women (OR = 0.75; 95% CI = 0.62-0.91; p = 0.003; dominant model). Similar results were found in the subgroup of endometrioid endometrial cancer (OR = 0.64; 95% CI = 0.51-0.79; p = 3.6 × 10 ; dominant model). The observed risk reduction was particularly strong among individuals in the range of 50-60 years of age (OR = 0.51; 95% CI = 0.33-0.78; p = 0.002; dominant model). In the different populations included in the ECAC dataset, the ORs varied from 0.85 to 1.05. Although five out of six populations revealed ORs <1.0, the overall estimate was nonsignificant and, as such, did not formally validate the findings in the Norwegian cohort.
The APOBEC3A/B deletion polymorphism is associated with a decreased risk of endometrial cancer in the Norwegian population.
一个常见的 30kb 缺失影响 APOBEC3A 和 APOBEC3B 基因，与人类癌症中 APOBEC 的活性增加和 APOBEC 相关的突变特征有关。这种缺失作为癌症风险因素的作用仍然存在争议。
我们在 1470 名挪威子宫内膜癌病例的样本中对 APOBEC3A/B 缺失进行了基因分型，并与 1918 名健康对照进行了比较。为了评估白种人群，我们通过 ECAC 联盟，在一个包含 4274 例病例和 18125 名健康对照的 GWAS 数据集中，挖掘了与缺失密切连锁的 SNP rs12628403 的基因型。
我们发现 APOBEC3A/B 缺失变体与挪威女性子宫内膜癌风险降低显著相关（OR = 0.75；95%CI = 0.62-0.91；p = 0.003；显性模型）。在子宫内膜样子宫内膜癌亚组中也发现了类似的结果（OR = 0.64；95%CI = 0.51-0.79；p = 3.6×10 -4 ；显性模型）。在 50-60 岁年龄范围内的个体中，观察到的风险降低尤其明显（OR = 0.51；95%CI = 0.33-0.78；p = 0.002；显性模型）。在 ECAC 数据集包含的不同人群中，OR 值从 0.85 到 1.05 不等。尽管六个群体中有五个群体的 OR 值<1.0，但总体估计值无统计学意义，因此，没有正式验证挪威队列的发现。
APOBEC3A/B 缺失多态性与挪威人群子宫内膜癌风险降低相关。
