Table 2.

Subgroup and sensitivity analyses

SubgroupsNo. studies (cases, controls)Heterogeneity PQ (I2)OR (95% CI); P valuePinteraction
All studies22 (6,424, 8,691)<0.001 (63)1.00 (0.90–1.10); 0.93NA
Cancer type
Colon cancer4 (574, 1,829)0.13 (47)1.21 (0.97–1.50); 0.10NA
Rectal cancer4 (293, 1,829)0.09 (54)1.13 (0.83–1.53); 0.44
Ethnicity of participants
Whites13 (4,961, 5,647)0.27 (17)0.93 (0.86–1.01); 0.080.03
East Asians7 (968, 2,031)0.004 (68)1.15 (0.93–1.43); 0.19
HWE in the control group
Controls in HWE21 (6,331, 8,596)<0.001 (61)1.01 (0.91–1.11); 0.890.07
Controls violating HWE1 (93, 95)NA0.59 (0.39–0.90); 0.01
Genotyping material*
Blood, normal tissue17 (6,048, 8,174)<0.001 (64)1.04 (0.94–1.15); 0.480.03
Tumor tissue5 (376, 517)0.31 (17)0.75 (0.60–0.94); 0.01
Genotyping quality control
Performed9 (4,621, 5,950)0.15 (34)0.99 (0.90–1.09); 0.860.79
Not performed or not reported13 (1,803, 2,741)<0.001 (72)0.95 (0.79–1.15); 0.63
Blind genotyping
Performed3 (165, 176)0.03 (71)1.06 (0.84–1.34); 0.630.53
Not performed or not reported19 (5,359, 6,931)<0.001 (64)0.97 (0.86–1.09); 0.61
Matching
Matched design7 (2,413, 3,257)<0.001 (79)1.03 (0.85–1.25); 0.770.43
No matching15 (4,011, 5,434)0.09 (35)0.96 (0.86–1.06); 0.39
Genotyping method
Other genotyping methods12 (4,675, 5,926)0.05 (44)0.91 (0.82–1.01); 0.080.03
RFLP10 (1,749, 2,765)0.01 (57)1.12 (0.96–1.30); 0.17

NOTE: Significant results are highlighted in bold.

Abbreviation: NA, not applicable.

  • *One study (38) explicitly stated that “normal mucosal cells were obtained from the cancer-free colorectal mucosa” and was included with the “blood/normal tissue.” Exclusion of this study did not substantially alter our results [blood/normal tissue group: OR, 1.03 (95% CI, 0.93–1.15) Pinteraction = 0.04]. All calculations are based on random effects models and allele-frequency comparisons. Supplementary Table S2 extends these analyses to dominant and recessive genetic models.