Impact of the APOBEC3A/B deletion polymorphism on risk of ovarian cancer

Gansmo, Liv Beathe; Sofiyeva, Nigar; Bjørnslett, Merete; Romundstad, Pål Richard; Hveem, Kristian; Vatten, Lars J.; Dørum, Anne; Lønning, Per Eystein; Knappskog, Stian

doi:10.1038/s41598-021-02820-z

Cited by 6 publications

(7 citation statements)

References 41 publications

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“…The A3A/B polymorphism confers a greater susceptibility to cancer by generating a hybrid transcript between A3A and A3B 3′UTR that is more stable and more highly expressed in cells [ 17 ]. A3A signature mutations are more common in cancer cells [ 43 ], and the A3A protein is able to hypermutate nuclear DNA and generate double-stranded DNA breaks (DSBs), cause apoptosis, and promote mutations in cancer-causing genes, contributing to tumorigenesis [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…The most important consequence is the deamination of cytidines (C) to uridines (U) [ 11 ], which generates double-strand breaks (DSB) or somatic mutations through transversions (C > G) or transitions (C > T) in the absence or failure of DNA repair [ 12 ]. These A3A signature mutations are found in bladder cancer [ 13 ], cervical cancer [ 4 , 14 ], breast cancer [ 15 , 16 ], ovarian cancer [ 17 ], head and neck cancer [ 18 ], and lung cancer [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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APOBEC3A/B Polymorphism Is Not Associated with Human Papillomavirus Infection and Cervical Carcinogenesis

et al. 2023

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The persistence of a high-risk Human papillomavirus (HPV-HR) infection of the cervix results in different manifestations of lesions depending on the immunologic capacity of the host. Variations in apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC)-like genes, such as the APOBEC3A/B deletion hybrid polymorphism (A3A/B), may contribute to cervical malignancy in the presence of HPV. The aim of this study was to investigate the association between the A3A/B polymorphism and HPV infection and the development of cervical intraepithelial lesions and cervical cancer in Brazilian women. The study enrolled 369 women, who were categorized according to the presence of infection and subdivided according to the degree of intraepithelial lesion and cervical cancer. APOBEC3A/B was genotyped by allele-specific polymerase chain reaction (PCR). As for the A3A/B polymorphism, the distribution of genotypes was similar between groups and among the analyzed subgroups. There were no significant differences in the presence of infection or development of lesions, even after exclusion of confounding factors. This is the first study to show that the A3A/B polymorphism is not associated with HPV infection and the development of intraepithelial lesions and cervical cancer in Brazilian women.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

APOBEC3A/B Polymorphism Is Not Associated with Human Papillomavirus Infection and Cervical Carcinogenesis

et al. 2023

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“…This finding was in line with previous data in other sample sets. 26 As such, the potential difference in results from APOBEC3A/B deletion analyses and rs12628403 analyses were considered negligible.…”

Section: Methodsmentioning

confidence: 99%

“…Notably, numerous tumor types have been assessed for the potential association between the APOBEC3A/B deletion variant and cancer risk. However, such studies have mainly provided contradicting results (Table S1 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ).…”

Section: Introductionmentioning

confidence: 99%

APOBEC3A/B deletion polymorphism and endometrial cancer risk

et al. 2022

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Background 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. Materials and Methods 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. Results 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 −5 ; 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. Conclusion The APOBEC3A/B deletion polymorphism is associated with a decreased risk of endometrial cancer in the Norwegian population.

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“…APOBEC3A/B has already been associated with a greater burden of mutational signatures consistent with APOBEC3 activity and with an increase in the risk of several types of cancer, including BC [ 26 , 27 , 28 , 29 , 30 ], suggesting that carriers of the deleted allele had greater APOBEC3A activity, since the deletion generates a more stable mRNA isoform for APOBEC3A [ 24 ]. However, it is interesting to point out that the APOBEC3B deletion polymorphism has also been associated with reduced risk for the development of certain types of cancer, such as lung cancer and ovarian cancer, in recent works in the literature [ 31 , 32 ]. Moreover, both APOBEC3A and APOBEC3B display cytidine-deaminase-independent roles in carcinogenesis that add complexity when it comes to comprehending their roles in cancer [ 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Involvement of APOBEC3A/B Deletion in Mouse Mammary Tumor Virus (MMTV)-like Positive Human Breast Cancer

2023

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The association between mouse mammary tumor virus (MMTV)-like sequences and human breast cancer (BC) is largely documented in the literature, but further research is needed to determine how they influence carcinogenesis. APOBEC3 cytidine deaminases are viral restriction factors that have been implicated in cancer mutagenesis, and a germline deletion that results in the fusion of the APOBEC3A coding region with the APOBEC3B 3′-UTR has been linked to increased mutagenic potential, enhanced risk of BC development, and poor prognosis. However, little is known about factors influencing APOBEC3 family activation in cancer. Thus, we hypothesized that MMTV infection and APOBEC3-mediated mutagenesis may be linked in the pathogenesis of BC. We investigated APOBEC3A/B genotyping, MMTV-like positivity, and clinicopathological parameters of 209 BC patients. We show evidence for active APOBEC3-mediated mutagenesis in human-derived MMTV sequences and comparatively investigate the impact of APOBEC3A/B germline deletion in MMTV-like env positive and negative BC in a Brazilian cohort. In MMTV-like negative samples, APOBEC3A/B deletion was negatively correlated with tumor stage while being positively correlated with estrogen receptor expression. Although APOBEC3A/B was not associated with MMTV-like positivity, samples carrying both MMTV-like positivity and APOBEC3A/B deletion had the lowest age-at-diagnosis of all study groups, with all patients being less than 50 years old. These results indicate that APOBEC3 mutagenesis is active against MMTV-like sequences, and that APOBEC3A/B deletion might act along with the MMTV-like presence to predispose people to early-onset BC.

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Impact of the APOBEC3A/B deletion polymorphism on risk of ovarian cancer

Cited by 6 publications

References 41 publications

APOBEC3A/B Polymorphism Is Not Associated with Human Papillomavirus Infection and Cervical Carcinogenesis

APOBEC3A/B Polymorphism Is Not Associated with Human Papillomavirus Infection and Cervical Carcinogenesis

APOBEC3A/B deletion polymorphism and endometrial cancer risk

Involvement of APOBEC3A/B Deletion in Mouse Mammary Tumor Virus (MMTV)-like Positive Human Breast Cancer

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