Abstract 1853P
Background
ATM (Ataxia-telangiectasia mutated) is the gene responsible for ataxia-telangiectasia syndrome. ATM-gene mutation carriers occur 1.4-2% in general population. ATM heterozygotes have an increased risk of developing cancers, especially breast cancer, as well as ischemic heart disease, which cause them to have shorter life expectancy.
Methods
The UK Biobank study cohort included 502,634 participants who were considered as middle and old age population (aged 40-69 years old), recruited via postal invitation to those who are registered with the UK National Health Service (NHS), living in England, Scotland and Wales. Participants provided informed consent for genotyping and data linkage to medical records. We limit our analysis to the 50,000 white Europeans who currently have exome data available. We utilise variant call format (VCF) provided by UK Biobank and variant effect predictor (VEP) to annotate ATM variants and prioritise a subset for analysis. We identify the individuals with ATM heterozygous mutations and analyse these data to evaluate the associations between ATM mutations and the development of cancers and cardiovascular disease at population level.
Results
We identify 113 ATM loss-of-function (LoF) mutations and 68 ATM missense mutations among 50,000 exome-sequenced individuals in the UK Biobank. Compared to the UK Biobank population, the prevalence of both prostate cancer (13.6% vs 3.7%, p=0.05) and female breast cancer (12.2% vs 5.7%, p=0.01) with pathogenic ATM mutations are significantly higher. The overall incidence of cancers in ATM-gene carriers is higher but not statistically different, comparing with UK Biobanks (20.1% vs 14.6%, p=0.16). In relation to cardiovascular risks, ATM gene mutations have statistically significant higher rates of cardiac chest pain and first-degree family history of cardiovascular disease than UK Biobanks (p=0.03 and 0.04, respectively).
Conclusions
ATM gene mutation carrier status is not associated with overall cancer risk. However, ATM gene mutation carriers are especially associated with prostate cancer and female breast cancer risks; in addition, it is associated with certain risks of cardiovascular disease in UK Biobank cohort.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.