Association of Germline Variation in Driver Genes with Breast Cancer Risk in Chilean Population
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Families
4.2. Control Population
4.3. SNPs Selection
4.4. Genotyping Analysis
4.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Inclusion Criteria | Families: n (%) |
---|---|
Three or more family members with breast and/or ovarian cancer | 148 (29.8%) |
Two family members with breast and/or ovarian cancer | 166 (33.6%) |
Single affected individual with breast cancer age ≤35 | 87 (17.9%) |
Single affected individual with breast cancer age 36–50 | 91 (18.7%) |
Total | 492 (100%) |
Genotype or Allele | Controls (%) (n = 1285) | All BC Cases (n = 492) | Families with ≥2 BC and/or OC Cases (n = 316) | Families with a Single Case, Diagnosis at ≤50 Years of Age (n = 176) | ||||||
---|---|---|---|---|---|---|---|---|---|---|
BC Cases (%) | OR [95% CI] | p-Value a | BC Cases (%) | OR [95% CI] | p-Value a | BC Cases (%) | OR [95% CI] | p-Value a | ||
rs832583 (MAP3K1) | ||||||||||
C/C | 473 (36.8) | 198 (40.3) | 1.0 (ref) | - | 140 (44.3) | 1.0 (ref) | - | 59 (33.3) | 1.0 (ref) | - |
C/A | 587 (45.7) | 219 (44.5) | 0.8 [0.6–1.0] | 0.32 | 132 (41.7) | 0.7 [0.5–0.9] | 0.04 | 86 (49.2) | 1.1 [0.8–1.5] | 0.42 |
A/A | 225 (17.4) | 75 (15.2) | 0.7 [0.5–1.0] | 0.14 | 44 (14.0) | 0.6 [0.4–0.9] | 0.03 | 31 (17.5) | 1.1 [0.7–1.7] | 0.72 |
C/A+A/A | 812 (63.2) | 294 (59.7) | 0.8 [0.6–1.0] | 0.18 | 176 (55.7) | 0.7 [0.5–0.9] | 0.01 | 117 (66.7) | 1.1 [0.8–1.6] | 0.40 |
Allele C | 1533 (59.6) | 615 (62.5) | 1.0 (ref) | - | 412 (65.2) | 1.0 (ref) | - | 204 (57.9) | 1.0 (ref) | - |
Allele A | 1037 (40.4) | 369 (37.5) | 0.8 [0.7–1.0] | 0.14 | 220 (34.8) | 0.7 [0.6–0.9] | 0.01 | 148 (42.1) | 1.0 [0.8–1.3] | 0.56 |
rs16865677 (SF3B1) | ||||||||||
G/G | 870 (67.7) | 319 (64.9) | 1.0 (ref) | - | 216 (68.5) | 1.0 (ref) | - | 103 (58.5) | 1.0 (ref) | - |
G/T | 364 (28.3) | 151 (30.6) | 1.1 [0.8–1.4] | 0.31 | 89 (27.9) | 0.9 [0.7–1.2] | 0.88 | 62 (35.2) | 1.4 [1.0–2.0] | 0.03 |
T/T | 51 (4.0) | 22 (4.5) | 1.1 [0.7–2.0] | 0.49 | 11 (3.6) | 0.8 [0.4–1.6] | 0.86 | 11 (6.3) | 1.8 [0.9–3.5] | 0.09 |
G/T+T/T | 415 (32.3) | 173 (35.1) | 1.1 [0.9–1.4] | 0.25 | 100 (31.5) | 0.9 [0.7–1.2] | 0.83 | 73 (41.5) | 1.4 [1.0–2.0] | 0.01 |
Allele G | 2104 (81.9) | 789 (80.1) | 1.0 (ref) | - | 521 (82.5) | 1.0 (ref) | - | 268 (76.1) | 1.0 (ref) | - |
Allele T | 466 (18.1) | 195 (19.9) | 1.1 [0.9–1.4] | 0.11 | 111 (17.5) | 0.9 [0.7–1.2] | 0.76 | 84 (23.9) | 1.4 [1.0–1.8] | 0.01 |
rs3819122 (SMAD4) | ||||||||||
A/A | 519 (40.4) | 143 (29.1) | 1.0 (ref) | - | 91 (28.8) | 1.0 (ref) | - | 52 (29.8) | 1.0 (ref) | - |
A/C | 576 (44.8) | 269 (54.5) | 1.6 [1.3–2.1] | <0.0001 | 166 (52.4) | 1.6 [1.2–2.1] | 0.0005 | 103 (58.4) | 1.7 [1.2–2.5] | 0.001 |
C/C | 190 (14.8) | 80 (16.3) | 1.5 [1.1–2.1] | 0.01 | 59 (18.8) | 1.7 [1.2–2.5] | 0.002 | 21 (11.8) | 1.1 [0.6–1.8] | 0.77 |
A/C+C/C | 766 (59.6) | 349 (70.9) | 1.6 [1.3–2.0] | <0.0001 | 225 (71.2) | 1.6 [1.2–2.1] | 0.0001 | 124 (70.2) | 1.6 [1.1–2.2] | 0.006 |
Allele A | 1614 (62.8) | 555 (56.4) | 1.0 (ref) | - | 348 (55.0) | 1.0 (ref) | - | 207 (59.0) | 1.0 (ref) | - |
Allele C | 956 (37.2) | 429 (43.6) | 1.3 [1.1–1.5] | 0.0005 | 284 (45.0) | 1.3 [1.1–1.6] | 0.0005 | 145 (41.0) | 1.1 [0.9–1.4] | 0.20 |
rs12456284 (SMAD4) | ||||||||||
A/A | 685 (53.3) | 227 (46.2) | 1.0 (ref) | - | 148 (46.9) | 1.0 (ref) | - | 79 (45.1) | 1.0 (ref) | - |
A/G | 427 (33.2) | 196 (39.9) | 1.3 [1.0–1.7] | 0.005 | 122 (38.7) | 1.3 [1.0–1.7] | 0.04 | 74 (41.8) | 1.5 [1.0–2.1] | 0.02 |
G/G | 173 (13.5) | 69 (13.9) | 1.2 [0.8–1.6] | 0.24 | 46 (14.4) | 1.2 [0.8–1.7] | 0.28 | 23 (13.1) | 1.1 [0.7–1.8] | 0.60 |
A/G+G/G | 600 (46.7) | 265 (53.8) | 1.3 [1.0–1.6] | 0.008 | 168 (53.1) | 1.2 [1.0–1.6] | 0.04 | 97 (54.9) | 1.4 [1.0–1.9] | 0.03 |
Allele A | 1797 (69.9) | 650 (66.1) | 1.0 (ref) | - | 418 (66.1) | 1.0 (ref) | - | 232 (66.0) | 1.0 (ref) | - |
Allele G | 773 (30.1) | 334 (33.9) | 1.2 [1.0–1.3] | 0.03 | 214 (33.9) | 1.1 [0.9–1.4] | 0.07 | 120 (34.0) | 1.2 [0.9–1.5] | 0.14 |
Genotype or Allele | Controls (%) (n = 1285) | Families with ≥2 BC and/or OC Cases (n = 165) | Families with ≥3 BC and/or OC Cases (n = 151) | ||||
---|---|---|---|---|---|---|---|
BC Cases (%) | OR [95% CI] | p-Value a | BC Cases (%) | OR [95% CI] | p-Value a | ||
rs832583 (MAP3K1) | |||||||
C/C | 473 (36.8) | 73 (44.2) | 1.0 (ref) | - | 67 (44.3) | 1.0 (ref) | - |
C/A | 587 (45.7) | 69 (41.7) | 0.7 [0.5–1.0] | 0.14 | 63 (41.6) | 0.7 [0.5–1.0] | 0.13 |
A/A | 225 (17.4) | 23 (14.1) | 0.7 [0.4–1.1] | 0.12 | 21 (14.1) | 0.6 [0.3–1.1] | 0.11 |
C/A+A/A | 812 (63.2) | 92 (55.8) | 0.7 [0.5–1.0] | 0.07 | 84 (55.7) | 0.7 [0.5–1.0] | 0.07 |
Allele C | 1533 (59.6) | 215 (65.0) | 1.0 (ref) | - | 197 (65.1) | 1.0 (ref) | - |
Allele A | 1037 (40.4) | 115 (35.0) | 0.7 [0.6–1.0] | 0.06 | 105 (34.9) | 0.7 [0.6–1.0] | 0.06 |
rs16865677 (SF3B1) | |||||||
G/G | 870 (67.7) | 114 (69.0) | 1.0 (ref) | - | 103 (68.0) | 1.0 (ref) | - |
G/T | 364 (28.3) | 45 (27.3) | 0.9 [0.6–1.3] | 0.85 | 43 (28.5) | 1.0 [0.6–1.4] | 1.0 |
T/T | 51 (4.0) | 6 (3.7) | 0.9 [0.4–2.0] | 1.0 | 5 (3.5) | 0.8 [0.3–2.1] | 1.0 |
G/T+T/T | 415 (32.3) | 51 (31.1) | 0.9 [0.6–1.3] | 0.78 | 48 (31.9) | 0.9 [0.6–1.4] | 1.0 |
Allele G | 2104 (81.9) | 273 (82.6) | 1.0 (ref) | - | 249 (82.3) | 1.0 (ref) | - |
Allele T | 466 (18.1) | 57 (17.4) | 0.9 [0.7–1.2] | 0.81 | 53 (17.7) | 0.9 [0.7–1.3] | 0.93 |
rs3819122 (SMAD4) | |||||||
A/A | 519 (40.4) | 41 (25.0) | 1.0 (ref) | - | 50 (32.9) | (ref) | - |
A/C | 576 (44.8) | 91 (55.3) | 2.0 [1.3–2.9] | 0.0004 | 74 (49.3) | 1.3 [0.9–2.0] | 0.13 |
C/C | 190 (14.8) | 33 (19.7) | 2.1 [1.3–3.5] | 0.001 | 27 (17.9) | 1.4 [0.8–2.4] | 0.16 |
A/C+C/C | 766 (59.6) | 124 (75.0) | 2.0 [1.3–2.9] | <0.0001 | 101 (67.1) | 1.3 [0.9–2.0] | 0.09 |
Allele A | 1614 (62.8) | 173 (52.6) | 1.0 (ref) | - | 174 (57.5) | (ref) | - |
Allele C | 956 (37.2) | 157 (47.4) | 1.5 [1.2–1.9] | 0.003 | 128 (42.5) | 1.2 [0.9–1.6] | 0.08 |
rs12456284 (SMAD4) | |||||||
A/A | 685 (53.3) | 77 (46.9) | 1.0 (ref) | - | 71 (46.8) | 1.0 (ref) | - |
A/G | 427 (33.2) | 64 (38.6) | 1.3 [0.9–1.8] | 0.11 | 59 (38.9) | 1.3 [0.9–1.9] | 0.12 |
G/G | 173 (13.5) | 24 (14.5) | 1.2 [0.7–2.0] | 0.48 | 21 (14.3) | 1.1 [0.6–1.9] | 0.58 |
A/G+G/G | 600 (46.7) | 88 (53.1) | 1.3 [0.9–1.8] | 0.11 | 80 (53.2) | 1.2 [0.9–1.8] | 0.14 |
Allele A | 1797 (69.9) | 192 (66.2) | 1.0 (ref) | - | 201 (66.6) | 1.0 (ref) | - |
Allele G | 773 (30.1) | 98 (33.8) | 1.1 [0.9–1.5] | 0.21 | 101 (33.4) | 1.1 [0.9–1.5] | 0.25 |
Composite Genotypes | All BC Cases (n = 488) | Families with ≥2 BC and/or OC Cases (n = 314) | Families with a Single Case, Diagnosis at ≤50 Years of Age (n = 174) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
SMAD4 | SF3B1 | Controls n = 1261 (%) | BC Cases (%) | OR [95% CI] | p-Value a | BC Cases (%) | OR [95% CI] | p-Value a | BC Cases (%) | OR [95% CI] | p-Value a |
rs3819122 | rs16865677 | ||||||||||
A/A | G/G | 336 (26.62) | 106 (21.72) | 1.0 (ref) | - | 66 (21.02) | 1.0 (ref) | - | 40 (22.99) | 1.0 (ref) | - |
A/A | G/T | 153 (12.12) | 34 (6.97) | 0.7 [0.4–1.1] | 0.12 | 20 (6.37) | 0.6 [0.3–1.1] | 0.16 | 14 (8.05) | 0.7 [0.4–1.4] | 0.53 |
A/A | T/T | 22 (1.74) | 9 (1.84) | 1.3 [0.5–2.9] | 0.52 | 5 (1.59) | 0.4 [0.1–2.0] | 0.39 | 4 (2.30) | 1.5 [0.5–4.6] | 0.51 |
A/C | G/G | 390 (30.90) | 165 (33.81) | 1.3 [1.0–1.7] | 0.045 | 113 (35.99) | 1.4 [1.0–2.0] | 0.023 | 52 (29.89) | 1.1 [0.7–1.7] | 0.65 |
A/C | G/T | 155 (12.28) | 86 (17.62) | 1.7 [1.2–2.4] | 0.0013 | 46 (14.65) | 1.5 [0.9–2.3] | 0.059 | 40 (22.99) | 2.1 [1.3–3.5] | 0.0021 |
A/C | T/T | 23 (1.82) | 12 (2.46) | 1.6 [0.7–3.4] | 0.22 | 6 (1.91) | 1.3 [0.5–3.3] | 0.60 | 6 (3.45) | 2.1 [0.8–5.7] | 0.12 |
C/C | G/G | 130 (10.30) | 47 (9.63) | 1.1 [0.7–1.7] | 0.53 | 37 (11.78) | 1.4 [0.9–2.2] | 0.12 | 10 (5.75) | 0.6 [0.3–1.3] | 0.31 |
C/C | G/T | 48 (3.80) | 28 (5.74) | 1.8 [1.1–3.0] | 0.023 | 21 (6.69) | 2.2 [1.2–3.9] | 0.012 | 7 (4.02) | 1.2 [0.5–2.8] | 0.64 |
C/C | T/T | 5 (0.40) | 1 (0.20) | 0.6 [0.07–5.49] | 1.00 | 0 (0.00) | 0.46 [0.02–8.42] | 1.00 | 1 (0.57) | 1.6 [0.1–14.8] | 0.49 |
Composite Genotypes | Families with ≥2 BC and/or OC Cases (n = 163) | Families with ≥3 BC and/or OC Cases (n = 151) | ||||||
---|---|---|---|---|---|---|---|---|
SMAD4 | SF3B1 | Controls n = 1261 (%) | BC Cases (%) | OR [95% CI] | p-Value a | BC Cases (%) | OR [95% CI] | p-Value a |
rs3819122 | rs16865677 | |||||||
A/A | G/G | 336 (26.62) | 31 (19.02) | 1.0 (ref) | - | 35 (23.18) | 1.0 (ref) | - |
A/A | G/T | 153 (12.12) | 7 (4.29) | 0.4 [0.2–1.1] | 0.10 | 13 (8.61) | 0.8 [0.4–1.5] | 0.63 |
A/A | T/T | 22 (1.74) | 3 (1.84) | 1.4 [0.4–5.2] | 0.46 | 2 (1.32) | 0.8 [0.1–3.8] | 1.00 |
A/C | G/G | 390 (30.90) | 62 (38.04) | 1.7 [1.0–2.7] | 0.019 | 51 (33.77) | 1.2 [0.7–1.9] | 0.36 |
A/C | G/T | 155 (12.28) | 26 (15.95) | 1.8 [1.0–3.1] | 0.037 | 20 (13.25) | 1.2 [0.6–2.2] | 0.54 |
A/C | T/T | 23 (1.82) | 3 (1.84) | 1.4 [0.4–4.9] | 0.48 | 3 (1.99) | 1.2 [0.3–4.3] | 0.72 |
C/C | G/G | 130 (10.30) | 20 (12.27) | 1.6 [0.9–3.0] | 0.10 | 17 (11.26) | 0.6 [0.3–1.3] | 0.31 |
C/C | G/T | 48 (3.80) | 11 (6.75) | 2.4 [1.1–5.2] | 0.03 | 10 (6.62) | 2.0 [0.9–4.3] | 0.10 |
C/C | T/T | 5 (0.40) | 0 (0.00) | 0.9 [0.05–18.00] | 1.00 | 0 (0.00) | 0.8 [0.04–15.90] | 1.00 |
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Morales-Pison, S.; Tapia, J.C.; Morales-González, S.; Maldonado, E.; Acuña, M.; Calaf, G.M.; Jara, L. Association of Germline Variation in Driver Genes with Breast Cancer Risk in Chilean Population. Int. J. Mol. Sci. 2023, 24, 16076. https://doi.org/10.3390/ijms242216076
Morales-Pison S, Tapia JC, Morales-González S, Maldonado E, Acuña M, Calaf GM, Jara L. Association of Germline Variation in Driver Genes with Breast Cancer Risk in Chilean Population. International Journal of Molecular Sciences. 2023; 24(22):16076. https://doi.org/10.3390/ijms242216076
Chicago/Turabian StyleMorales-Pison, Sebastián, Julio C. Tapia, Sarai Morales-González, Edio Maldonado, Mónica Acuña, Gloria M. Calaf, and Lilian Jara. 2023. "Association of Germline Variation in Driver Genes with Breast Cancer Risk in Chilean Population" International Journal of Molecular Sciences 24, no. 22: 16076. https://doi.org/10.3390/ijms242216076