Background
Methods
Study population
Cases | Controls | Total | |
---|---|---|---|
Gender | |||
Male | 35 (42%) | 127 (39%) | 162 |
Female | 48 (58%) | 197 (61%) | 245 |
Age at exposure | |||
< 1 y | 9 (11%) | 73 (22.5%) | 82 |
1–1.9 y | 14 (17%) | 46 (14%) | 60 |
2–2.9 y | 9 (11%) | 40 (12%) | 49 |
3–3.9 y | 17 (20%) | 40 (12%) | 57 |
4–4.9 y | 9 (11%) | 43 (13%) | 52 |
5–5.9 y | 4 (5%) | 18 (5.5%) | 22 |
6–9 y | 13 (15%) | 35 (11%) | 48 |
10–14 y | 8 (10%) | 29 (10%) | 37 |
Age at diagnosis | |||
< 11.5 y | 24 (29%) | 119 (37%) | 143 |
11.5–14.9 y | 33 (40%) | 120 (37%) | 153 |
15+ y | 26 (31%) | 85 (26%) | 111 |
Genotyping
Selection of SNPs in DNA repair related genes
Statistical analyses
Results
SNP-based analysis
NER | BER | MMR | SSA | NHEJ | MMEJ | HR | FANCONI | DR | TLS | |
---|---|---|---|---|---|---|---|---|---|---|
NER | 14 [30]
| |||||||||
BER | 8 [19]
| 17 [47]
| ||||||||
MMR | 3 [9]
| 6 [21]
| 10 [47]
| |||||||
SSA | 1 [2]
| 1 [9]
| 2 [13]
| 4 [16]
| ||||||
NHEJ | - | 1 [5]
| - | - | 4 [13]
| |||||
MMEJ | 5 [8]
| 3 [4]
| 2 [2]
| 1 [2]
| - | 7 [13]
| ||||
HR | - | 2 [10]
| 1 [1]
| 1 [1]
| 1 [5]
| 2 [5]
| 13 [47]
| |||
FANCONI | 2 [4]
| - | - | 1 [2]
| - | 2 [4]
| 4 [21]
| 7 [34]
| ||
DR | - | - | - | - | - | - | - | - | 1 [4]
| |
TLS | 1 [3]
| 1 [3]
| 1 [3]
| - | - | - | 2 [9]
| 3 [18]
| - | 4 [21]
|
Gene | DNA repair module | SNP | Nucleotide change | Location relative to gene | MAF in cases | MAF in controls | Genetic model | OR (95% CI) a
|
P
a
|
P
corr
b
|
---|---|---|---|---|---|---|---|---|---|---|
MGMT
| DR | rs2296675 | A > G | Intronic | 0.21 | 0.10 | ||||
Risk per G allele c
| 2.54 (1.50, 4.30) | 0.0006 | 0.05 | |||||||
A/G + GG versus A/A d
| 2.72 (1.48, 5.03) | 0.001 | 0.13 | |||||||
G/G versus A/G + AA e
| 5.30 (1.25, 22.48) | 0.02 | 1 | |||||||
XRCC5
| NHEJ | rs1051685 | A > G | 3’UTR | 0.09 | 0.16 | ||||
Risk per G allele c
| 0.39 (0.20, 0.78) | 0.008 | 0.73 | |||||||
A/G + GG versus A/A d
| 0.39 (0.18, 0.83) | 0.01 | 1 | |||||||
G/G versus A/G + AA e
| N/A | N/A | N/A | |||||||
ERCC5
| BER, NER | rs1047768 | C > T | Coding (p.His46His) | 0.49 | 0.39 | ||||
Risk per T allele c
| 1.58 (1.06, 2.35) | 0.02 | 1 | |||||||
C/T + T/T versus C/C d
| 1.89 (1.05, 3.42) | 0.03 | 1 | |||||||
T/T versus C/T + CC e
| 1.80 (0.88, 3.66) | 0.11 | 1 | |||||||
PARP1
| BER, HR, NHEJ | rs747659 | C > T | Intergenic | 0.12 | 0.18 | ||||
Risk per T allele c
| 0.49 (0.26, 0.94) | 0.03 | 1 | |||||||
C/T + T/T versus C/C d
| 0.49 (0.25, 0.97) | 0.04 | 1 | |||||||
T/T versus C/T + CC e
| N/A | N/A | N/A | |||||||
PCNA
| BER, MMR, NER, TLS | rs17349 | C > T | 5’UTR | 0.14 | 0.08 | ||||
Risk per T allele c
| 1.98 (1.07, 3.68) | 0.03 | 1 | |||||||
C/T + T/T versus C/C d
| 1.93 (0.96, 3.85) | 0.06 | 1 | |||||||
T/T versus C/T + CC e
| 8.29 (0.88, 78.3) | 0.06 | 1 | |||||||
PMS2
| MMR | rs3735295 | G > A | Intronic | 0.12 | 0.19 | ||||
Risk per A allele c
| 0.52 (0.28, 0.97) | 0.04 | 1 | |||||||
G/A + A/A versus G/G d
| 0.49 (0.24, 1.00) | 0.05 | 1 | |||||||
A/A versus G/A + A/A e
| 0.33 (0.05, 2.07) | 0.24 | 1 | |||||||
OGG1
| BER | rs125701 | G > A | Intergenic | 0.27 | 0.21 | ||||
Risk per A allele c
| 1.65 (1.01, 2.68) | 0.04 | 1 | |||||||
G/A + A/A versus G/G d
| 1.87 (1.03, 3.40) | 0.04 | 1 | |||||||
A/A versus G/A + A/A e
| 1.73 (0.47, 6.37) | 0.41 | 1 |
Gene-based analysis
Chr | Gene | Start | Stop | Number of tested SNPs | Number of simulations | Test |
P
Gene
| Best SNP |
P
per allele
|
---|---|---|---|---|---|---|---|---|---|
10 |
MGMT
| 131,215,453 | 131,615,783 | 4 | 1e + 05 | 13.93 | 0.008 | rs2296675 | 0.0006 |
13 |
ERCC5
| 103,448,190 | 103,578,351 | 2 | 1e + 06 | 9.39 | 0.01 | rs1047768 | 0.02 |
20 |
PCNA
| 5,045,598 | 5,157,268 | 3 | 1e + 05 | 9.30 | 0.05 | rs17349 | 0.03 |
7 |
PMS2
| 5,962,869 | 6,098,737 | 4 | 1000 | 8.70 | 0.09 | rs3735295 | 0.04 |
1 |
PARP1
| 226,498,391 | 226,645,801 | 5 | 1000 | 11.05 | 0.11 | rs747659 | 0.03 |
3 |
OGG1
| 9,741,627 | 9,858,353 | 2 | 1000 | 4.30 | 0.13 | rs125701 | 0.05 |
2 |
XRCC5
| 216,924,019 | 217,121,016 | 4 | 1000 | 7.79 | 0.13 | rs1051685 | 0.008 |