Table 1.
Gene penetrance as reported in selected publications for some breast cancer predisposition genes
| Gene | Study design | Ethnicity | No. cases | No. controls | OR; RR | 95 % CI | Percentage cumulative risk to age 70 years for carriers living in USA (95 % CI) | Comment | References |
|---|---|---|---|---|---|---|---|---|---|
| BLM c.1642C>T (Q548X) | Case: Control | Russian | 1498 | 1093 | OR 6.28 | 1.52–42.18 | 43 (12.7–97.7) | Some selection for high risk; OR calculated using only unselected cases (n = 879). Mean age for cases, 51 years; range 24–81 years. Controls were cancer-free blood donors | [2] |
| BRIP1 truncating mutations | Case: Control | United Kingdom | 2012 | 2081 | RR 2.0 | 1.2–3.2 | 16.4 (10.2–24.9) | BRCA1/2 negative women with breast cancer and family history of breast and/or ovarian cancer. Relative risks in whole cohort. No ages provided. Controls from a 1958 birth cohort collection, not selected for any other characteristic | [3] |
| BRIP1 truncating mutations | Case: Control | United Kingdom | Unknown | 2081 | RR 3.5 | 1.9–5.7 | 26.9 (15.6–40) | Subset of cohort of women with breast cancer and family history of breast and/or ovarian cancer. Relative risk for carriers < 50. Controls from a 1958 birth cohort collection, not selected for any other characteristic | [3] |
| NBN 657del5 | Meta-analysis of 9 case:control studies | Multinational | 7534 | 14,034 | OR 2.63 | 1.76–3.93 | 21 (14.6–29.7) | Meta-analysis of 9 studies | [4] |
| NBN 657del5 | Case: Control | Polish | 66 | 1620 | OR 8.36 | 2.57–27.27 | 52.7 (20.6–91.3) | Cases diagnosed <40 years. Controls were anonymous donors, not otherwise described | [5] |
| NBN 657del5 | Case: Control | Polish | 221 | 1620 | OR 4.27 | 1.67–10.89 | 31.8 (13.9–62.3) | Cases 40–50 years. Controls were anonymous donors, not otherwise described | [5] |
| NBN 657del5 | Case: Control | Polish | 341 | 1620 | OR 2.4 | 0.91–6.35 | 19.3 (7.8–43.4) | Cases ≥ 50 years. Controls were anonymous donors, not otherwise described | [5] |
| NBN 657del5 | Case: Control | Polish | 562 | 1620 | OR 3.13 | 1.4–7.00 | 24.4 (11.8–46.6) | All (unselected) cases. Age range 24–81 years; median 52 years | [5] |
| RAD50 687delT | Case: Control | Finnish | 317 | 1000 | OR 4.3 | 1.5–12.5 | 32 (12.6–67.3) | Unselected cases. Mean age of cancer, 58 years; range 29–95 years. Controls were anonymous cancer-free blood donors | [6] |
| RECQL c.1667_1667 + 3delACTA | Case: Control | Polish | 13,136 | 4702 | OR 5.4 | 1.3–46 | 38.3 (11.0–98.4) | Unselected cases. Age ranges not provided. Controls not selected for cancer or family history | [7] |
Given the discordance of risk estimates across studies, caution is warranted in clinical interpretation (see “Discussion”). Additional new studies and estimates are emerging rapidly for specific genes
CI confidence interval, OR odds ratio, RR relative risk