Table 1.
Contribution of ATM variants in breast cancer susceptibility in studies presented at the workshop.
| Country | Study | Speaker | Population | Main findings | Reference |
|---|---|---|---|---|---|
| Norway | Hereditary Cancer Biobank | M. Dominguez Valentin (Oslo University Hospital) | 1,967 familial cancer cases and negative for pathogenic variants in the BRCA1/2, PTEN, TP53 or MMR genes. | 11 LoF carriers were identified among 1967 cases. No reported OR associated with ATM variants. |
Unpublished data |
| Macedonia | Macedonian Breast Cancer Association Study (MBCAS) | D. Plaseska-Karanfilska (Macedonian Academy of Sciences and Arts, Skopje) | 390 probands from HBOC families, compared alleles frequencies to that of GnomAD and FLOSSIES public databases | 7 LoF carriers among cases (1.8%), all were 40 years and less at breast cancer diagnosis: 4 also with a BRCA1/2 pathogenic variant and 1 with an EPCAM pathogenic variant. Except for BRCA1/ATM double carrier, all had an ER+ breast tumor. 22 carriers (5,6%) of rare missense variants, classified as VUS according to the ACMG guidelines. No reported OR associated with ATM variants. |
Unpublished data |
| France | GENE SISters (GENESIS) | F. Lesueur (U900-Institut Curie, Paris) | 1,207 cases from HBOC families and negative for pathogenic BRCA1/2 variants & 1,199 unrelated controls | Focus on variants with MAF<0.005. 16 LoF carriers (1.3%) and 61 predicted deleterious missense variants (5.0%) among cases. LoF carriers had a higher risk than carriers of a rare missense (ORLoF= 17.4 (2.3–132) vs. ORmissense=1.6 (1.0–2.3); PHet=0.002). Mean age at diagnosis was 50.0 for LOF carriers and 50.9 for missense variants carriers. 85.5% of carriers (LoF + missense) had an ER+ breast tumor. |
[33] |
| Germany | German consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) | N. Herold (University of Cologne) | 5,589 cases from HBOC families & 2189 controls | 81 LoF carriers among cases (1.5%), 71 unilateral, 10 bilateral. Associated OR=3.63, 95% CI: 2.67–4.94; median age at diagnosis for carriers was 45 years (range 27–80 years), 71.6% of carriers were under 50 years at diagnosis and 34.6% under age 40. |
[95] |
| USA | CAnceR RIsk Estimates Related to Susceptibility (CARRIERS) | D. Goldgar (Hunstman Cancer Institute, Salt Lake City) | 32,247 cases & 32,544 controls from 12 population-based cohort or case-control studies | mean age at diagnosis=62 years OR associated with pathogenic ATM variants (AGL variant classification; largely equivalent to ClinVar) = 1.8 (95% CI: 1.5 – 2.3); increased risk in women diagnosed with breast cancer before age 60 (OR=2.6, 95% CI: 1.9,3.6). No evidence of association between ATM variants and ER-breast tumour. |
[30] |
HBOC, Hereditary Breast and Ovarian Cancer; AGL, Ambry Genetic Laboratory; ER+, estrogen receptor positive tumor; ER−, estrogen negative tumor; MAF, minor allele frequency; OR, Odds ratio.