Criteria / Score
Representativeness of cases
Consecutive/randomly recruitment from case population / 2
No method of selection stated / 0
Ascertainment of colorectal cancer
Histological confirmation at the Department of Pathology / 2
Not described / 0
Representativeness of controls
Consecutive/randomly recruitment from the same sampling / 1
No method of selection stated / 0
Characteristics of control
Good health without any sorts of diseases / 1
No family history of CRC / 1
Not described / 0
Sample size
≥1000 / 1
<1000 / 0
Genotyping examination
Method control* / 2
Not described / 0
Total 10
*Methodcontrol: Ifthe genotyping was done under blinded condition, using randomrepeat, negative or positive control, or confirmed using two or more genetic methods, a score of two points could be awarded. Otherwise, it scores zero point.
Table S2.Exon SNPs of MLH1 in CRCRSID / Genomic / Transcript / Consequence / Region / References＊ / Major Findings / NCBI / functional domain
rs41295280 / g.5263G>C / c.65G>C / p.Gly22Ala / exon 1 / [1] / benign / vus / ATPase domain
rs63749939 / g.8353G>A / c.200G>A / p.Gly67Glu / exon 2 / [1] / pathogenic / pathogenic / ATP binding and hydrolysis
rs41295282 / g.1267A>G / c.277A>G / p.Ser93Gly / exon 3 / [1] / benign / vus / ATPase domain
rs28930073 / g.18655G>C / c.394G>C / p.Asp132His / exon 5 / [2-6] / no significant association/not observed/risk factor to SCRC in China / other / ATPase domain
rs1799977 / g.237284A>G / c.655A>G / p.Ile219Val / exon 8 / [3, 4, 7-15] / no significant association / benign / ATPase domain
rs267607808 / g.32001C>T / c.925C>T / p.Pro309Ser / exon 11 / [1] / benign / vus / ATPase domain
rs63750447 / g.37400T>A / c.1151T>A / p.Val384Asp / exon 12 / [3, 10, 16-19] / low-penetrance risk alleles for CRC / with untested allele / none
rs41294980 / g.37466G>A / c.1217G>A / p.Ser406Asn / exon 12 / [1, 9] / benign/neutral variant / other / none
rs267607824 / g.37377T>C / c.1128T>C / p.Asp376Asp / exon 12 / [20] / significantly associated with HNPCC and early-onset CRC / benign / none
rs41295284 / g.59258T>A / c.1820T>A / p.Leu607His / exon 16 / [1] / benign / vus / PMS2/MLH3/PMS1interaction domain,interaction with hExo1
rs35502531 / g.59290:59291 / c.1852_1853 delAAinsGC / p.Lys618Ala / exon 16 / [1, 9] / benign/no significant association / vus / PMS2/MLH3/PMS1interaction domain,interaction with hExo1
rs1800146 / g.600230G>T / c.1959G>T / p.Leu653Leu / exon 17 / [9] / neutral variant / benign / PMS2/MLH3/PMS1interaction domain
rs63750217 / g.60606G>A / c.2041G>A / p.Ala681Thr / exon 18 / [1] / pathogenic / pathogenic / PMS2/MLH3/PMS1interaction domain
rs63750702 / g.60631A>G / c.2066A>G / p.Gln689Arg / exon 18 / [1] / possible protective effect / benign / PMS2/MLH3/PMS1interaction domain
rs35831931 / g.62179G>A / c.2146G>A / p.Val716Met / exon 19 / [1] / possible protective effect / other / PMS2/MLH3/PMS1interaction domain
rs2020873 / g.62185C>T / c.2152C>T / p.His718Tyr / exon 19 / [1, 5] / benign/not observed in the German population / benign / PMS2/MLH3/PMS1interaction domain
rs140195825 / g.62285A>G / c.2252A>G / p.Lys751Arg / exon 19 / [1] / benign / likely benign / none
＊References in Table S2 were separately listed in the supplementary materials.
Table S3. ORs (95% CI) of sensitivity analysis for MLH1 polymorphisms on CRC risks of different comparison modelsCodominant:AA VS BB / Codominant:AB VS BB / Dominant:AA+AB VS BB / Recessive:AA VS AA+AB
Omitted study / OR / 95% CI / POR / OR / 95% CI / POR / OR / 95% CI / POR / OR / 95% CI / POR
rs1800734
Campbellet al.
(2009) / 1.120 / 0.921-1.363 / 0.256 / 1.063 / 0.965-1.171 / 0.212 / 1.075 / 0.971-1.190 / 0.162 / 1.091 / 0.990-1.202 / 0.080
Ito et al. (1999) / 1.106 / 0.927-1.319 / 0.046 / 1.056 / 0.970-1.150 / 0.221 / 1.066 / 0.974-1.168 / 0.166 / 1.085 / 0.990-1.190 / 0.082
Muniz-Mendozaet al. (2012) / 1.107 / 1.006-1.219 / 0.038 / 1.052 / 1.006-1.101 / 0.027 / 1.076 / 0.990-1.169 / 0.085 / 1.105 / 1.008-1.213 / 0.034
Samowitzet al. (2008) / 1.117 / 0.920-1.356 / 0.263 / 1.064 / 0.968-1.170 / 0.197 / 1.076 / 0.973-1.189 / 0.153 / 1.089 / 0.989-1.199 / 0.086
Tulupova et al. (2005) / 1.130 / 0.941-1.259 / 0.191 / 1.053 / 0.960-1.155 / 0.274 / 1.068 / 0.969-1.176 / 0.183 / 1.099 / 1.001-1.207 / 0.048
Raptis et al. (2007) / 1.121 / 0.926-1.357 / 0.242 / 1.041 / 0.918-1.144 / 0.400 / 1.056 / 0.956-1.166 / 0.080 / 1.097 / 0.997-1.207 / 0.057
Zhang et al. (2011) / 1.135 / 0.945-1.364 / 0.175 / 1.054 / 1.007-1.103 / 0.023 / 1.076 / 0.984-1.177 / 0.107 / 1.088 / 0.989-1.197 / 0.084
Shin et al. (2002) / 1.099 / 0.918-1.316 / 0.302 / 1.053 / 0.964-1.149 / 0.255 / 1.062 / 0.968-1.164 / 0.202 / 1.084 / 0.987-1.190 / 0.092
Allan et al. (2008) / 1.101 / 0.916-1.323 / 0.306 / 1.036 / 0.948-1.133 / 0.433 / 1.048 / 0.954-1.151 / 0.328 / 1.088 / 0.990-1.195 / 0.079
Whiffin et al. (2011) / 1.127 / 0.909-1.398 / 0.275 / 1.053 / 0.943-1.176 / 0.356 / 1.069 / 0.953-1.200 / 0.256 / 1.100 / 0.977-1.239 / 0.116
Koessler et al. (2008) / 1.114 / 0.940-1.383 / 0.182 / 1.064 / 0.964-1.174 / 0.218 / 1.078 / 0.974-1.195 / 0.147 / 1.110 / 1.007-1.224 / 0.036
Chen et al. (2007) / 1.098 / 0.921-1.309 / 0.297 / 1.044 / 0.998-1.093 / 0.062 / 1.056 / 0.963-1.137 / 0.289 / 1.090 / 0.993-1.195 / 0.069
van Roon et al. (2010) / 1.072 / 0.974-1.180 / 0.157 / 1.045 / 0.999-1.094 / 0.054 / 1.050 / 1.006-1.097 / 0.023 / 1.075 / 0.980-1.179 / 0.126
rs1799977
Campbell et al. (2009) / 0.947 / 0.866-1.036 / 0.237 / 1.004 / 0.951-1.060 / 0.894 / 0.994 / 0.944-1.047 / 0.824 / 0.948 / 0.870-1.033 / 0.221
Kim et al. (2004） / 0.960 / 0.883-1.043 / 0.336 / 1.001 / 0.951-1.053 / 0.974 / 0.994 / 0.948-1.043 / 0.814 / 0.961 / 0.887-1.041 / 0.329
Mei et al. (2006） / 0.959 / 0.882-1.042 / 0.322 / 1.000 / 0.951-1.052 / 0.999 / 0.993 / 0.946-1.042 / 0.771 / 0.960 / 0.886-1.040 / 0.316
Muniz-Mendoza et al. (2012) / 0.958 / 0.881-1.041 / 0.312 / 0.999 / 0.949-1.051 / 0.967 / 0.991 / 0.945-1.040 / 0.722 / 0.959 / 0.886-1.039 / 0.307
Berndt et al.（2007） / 0.967 / 0.888-1.052 / 0.430 / 1.001 / 0.951-1.054 / 0.969 / 0.996 / 0.948-1.046 / 0.865 / 0.968 / 0.893-1.049 / 0.427
Raptis et al.（2007） / 0.966 / 0.885-1.054 / 0.434 / 1.011 / 0.958-1.067 / 0.388 / 1.004 / 0.954-1.056 / 0.888 / 0.963 / 0.886-1.047 / 0.378
Picelli et al.（2010） / 0.936 / 0.856-1.023 / 0.145 / 0.985 / 0.933-1.010 / 0.578 / 0.977 / 0.927-1.028 / 0.366 / 0.945 / 0.867-1.029 / 0.190
Picelli et al.（2013） / 1.009 / 0.889-1.146 / 0.888 / 1.026 / 0.953-1.106 / 0.496 / 1.025 / 0.955-1.101 / 0.490 / 1.000 / 0.885-1.130 / 1.000
Christensen et al.（2008） / 0.963 / 0.886-1.049 / 0.391 / 0.999 / 0.949-1.053 / 0.976 / 0.994 / 0.946-1.044 / 0.797 / 0.965 / 0.890-1.048 / 0.400
rs63750447
Kim et al.（2004） / 2.518 / 1.728-3.669 / 0.000 / 2.529 / 1.736-3.684 / 0.000
Mei et al. (2006) / 2.351 / 1.603-3.446 / 0.000 / 2.361 / 1.610-3.462 / 0.000
Ohsawa et al. (2009） / 2.085 / 1.434-3.031 / 0.000 / 2.085 / 1.434-3.031 / 0.000
Zhang et al. (2004） / 2.151 / 1.617-3.714 / 0.000 / 2.463 / 1.625-3.733 / 0.000
Wang et al.（2010） / 2.180 / 1.519-3.129 / 0.000 / 2.189 / 1.525-3.142 / 0.000
Wang et al.（1998） / 2.200 / 1.540-3.143 / 0.000 / 2.208 / 1.546-3.155 / 0.000
Wang et al.（2000） / 2.276 / 1.573-3.300 / 0.000 / 2.288 / 1.580-3.313 / 0.000
References in Table S2
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