Introduction
Methods
Study search
Inclusion | Exclusion |
---|---|
Examines the relationship between a low penetrance genetic risk modifier and colorectal cancer in Lynch syndrome | Case or review studies |
Case control study | Studies with insufficient data to determine OR |
At least 40 cases and 40 controls | Animal or tissue based studies |
Study participants have been randomly selected | Duplicate studies (use of same study participants and data but published in two different papers) |
Confirmed diagnosis of Lynch syndrome either through clinical criteria or mutations to MMR genes | Control population is not in Hardy–Weinburg equilibrium |
Confirmed diagnosis of colorectal cancer | |
Full article published in English in a peer reviewed journal |
Data extraction
Statistics
Results
Gene | Polymorphism | Minor allele | MAF | OR (95% CI) | Study |
---|---|---|---|---|---|
P53
| Rs1042522 | C | 0.22 | 1.16 (0.64–2.11) | Chen et al. [25] |
Rs1042522 | C | 0.23 | 0.87 (0.56–13.6) | Talseth et al. [26] | |
Rs1042522 | C | 0.21 | 1.04 (0.63–1.72) | Sotamaa et al. [27] | |
Rs1042522 | C | 0.23 | 0.74 (0.37–1.47) | Jones et al. [28] | |
CYP1A1
| Rs4646903 | C | 0.14 | 1.17 (0.71–1.91) | Pande et al. [29] |
Rs4646903 | C | 0.08 | 2.86 (1.31–6.21) | Talseth et al. [30] | |
Rs4646903 | C | 0.11 | 0.91 (0.65–1.27) | Houlle et al. [31] | |
8q23.3
| Rs1689766 | C | 0.07 | 1.34 (0.92–1.96) | Win et al. [32] |
Rs1689766 | C | 0.08 | 1.06 (0.69–1.64) | Talseth-Palmer et al. [33] | |
Rs1689766 | C | 0.07 | 1.25 (0.85–1.84) | Houlle et al. [31] | |
Rs1689766 | C | 0.10 | 1.10 (0.71–1.71) | Wijnen et al. [34] | |
11q23.1
| Rs3802842 | T | 0.29 | 1.08 (0.88–1.33) | Win et al. [32] |
Rs3802842 | T | 0.26 | 1.09 (0.84–1.42) | Talseth-Palmer et al. [33] | |
Rs3802842 | T | 0.28 | 1.03 (0.82–1.30) | Houlle et al. [31] | |
Rs3802842 | T | 0.25 | 1.18 (0.87–1.60) | Wijnen et al. [34] | |
8q24.1
| Rs6983267 | A | 0.47 | 0.88 (0.72–1.06) | Win et al. [32] |
Rs6983267 | A | 0.48 | 1.01 (0.80–1.27) | Talseth-Palmer et al. [33] | |
Rs6983267 | A | 0.47 | 0.94 (0.72–1.23) | Wijnen et al. [34] | |
10p14
| Rs10795668 | C | 0.30 | 0.98 (0.78–1.23) | Win et al. [32] |
Rs10795668 | C | 0.33 | 0.95 (0.74–1.21) | Talseth-Palmer et al. [33] | |
Rs10795668 | C | 0.33 | 1.06 (0.80–1.41) | Wijnen et al. [34] | |
15q13.3
| Rs4779584 | T | 0.22 | 0.96 (0.76–1.20) | Win et al. [32] |
Rs4779584 | T | 0.23 | 0.93 (0.70–1.24) | Talseth-Palmer et al. [33] | |
Rs4779584 | T | 0.20 | 0.84 (0.59–1.19) | Wijnen et al. [34] | |
CCND1
| Rs9344 | A | 0.50 | 1.33 (0.97–1.82) | Talseth-Palmer et al. [33] |
Rs9344 | A | 0.44 | 1.05 (0.64–1.73) | Chen et al. [25] | |
Rs9344 | A | 0.42 | 1.02 (0.73–1.42) | Krüger et al. [35] | |
Rs9344 | A | 0.57 | 1.37 (0.84–2.24) | Bala et al. [36] | |
Rs9344 | A | 0.45 | 1.06 (0.64–1.77) | Zexevic et al. [37] | |
Rs9344 | A | 0.44 | 1.01 (0.55–1.86) | Kong et al. [38] | |
GSTT1
| – | Null | 0.23 | 0.80 (0.44–1.43) | Pande et al. [33] |
– | Null | 0.21 | 1.08 (0.56–2.08) | Talseth et al. [35] | |
– | Null | 0.50 | 1.68 (0.80–3.55) | Felix et al. [39] | |
GSTM1
| – | Null | 0.44 | 0.95 (0.58–1.56) | Pande et al. [33] |
– | Null | 0.55 | 1.00 (0.59–1.71) | Talseth et al. [35] | |
– | Null | 0.15 | 1.40 (0.50–3.93) | Felix et al. [37] | |
– | Null | 0.40 | 0.85 (0.39–1.87) | Jones et al. [40] |
Gene | Polymorphism | Minor allele | Number of included studies | Pooled cases/controls | OR (95% CI) | I2 values (%) |
---|---|---|---|---|---|---|
P53
| Rs1042522 | C | 4 | 345/281 | 0.95 (0.73–1.23) | 0.00 |
CYP1A1
| RS4646903 | C | 3 | 567/656 | 1.33 (0.72–2.46) | 77.07 |
– | Rs1689766 | C | 4 | 1127/1768 | 1.20 (0.98–1.47) | 0.00 |
– | Rs3802842 | T | 4 | 1117/1749 | 1.08 (0.96–1.22) | 0.00 |
– | Rs6983267 | A | 3 | 775/1321 | 0.93 (0.82–1.06) | 0.00 |
– | Rs10795668 | C | 3 | 706/1247 | 0.99 (0.86–1.14) | 0.00 |
– | Rs4779584 | T | 3 | 776/1333 | 0.92 (0.79–1.08) | 0.00 |
CCND1
| Rs9344 | A | 6 | 733/461 | 0.87 (0.73–1.03) | 0.00 |
GSTT1
| – | Null | 3 | 279/325 | 1.06 (0.73–1.55) | 13.92 |
GSTM1
| – | Null | 4 | 321/385 | 0.99 (0.72–1.35) | 0.00 |
Subgroup analysis
Gender
Polymorphism | Minor allele | Male OR (95% CI) | Female OR (95% CI) | Male vs. Female OR (95% CI) |
---|---|---|---|---|
Rs1689766 | C | 1.53 (1.12–2.10) | 0.98 (0.68–1.39) | 1.68 (1.18–2.41) |
Rs3802842 | T | 1.15 (0.95–1.41) | 1.01 (0.83–1.22) | 1.16 (0.94–1.43) |
MMR gene mutation subtypes
Sensitivity analysis
Publication bias
Discussion
Meta-analysis
Systematic review
Gene | Polymorphism | Minor allele | MAF | OR (95% CI) | Study |
---|---|---|---|---|---|
CYP17A1
| Rs743572 | C | 0.39 | 1.83 (1.11–3.00) | Campbell et al. [53] |
KIF20A
| Rs10038448 | G | 0.21 | 1.46 (1.07–1.99) | Chen et al. [54] |
CDC25C
| Rs6874130 | C | 0.22 | 1.47 (1.08–2.00) | Chen et al. [54] |
KDM3B/FAM53C
| Rs3734168 | A | 0.17 | 1.40 (1.00–1.96)a
| Chen et al. [25] |
SMAD7
| Rs4939827 | T | 0.49 | 1.27 (1.04–1.57) | Win et al. [32] |