Evaluation of association studies, a systematic review and meta-analysis
of CYP1A1 polymorphisms, and colorectal cancer risk
Abstract
Backgroud: 37 publications and seven previous meta-analyses have been
reported to investigate the correlation between CYP1A1 T3801C and A2455G
polymorphisms with CRC risk. However, the results were contradictory.
Original studies were not involved in previously published
meta-analyses. Moreover, their meta-analyses did not evaluate positive
results to identify multiple comparisons. Objectives: We performed an
updated meta-analysis and systematically evaluated the published
meta-analyses on the association between CYP1A1 T3801C and A2455G
polymorphism with CRC susceptibility. Results: CYP1A1 T3801C
polymorphism was not associated with CRC risk when all the selected
studies were merged. However, subgroup analyses according to ethnicity,
geographic region, location of CRC, gender and smoking, showed a
significant association in rectal cancer and females. However, after
BFDP correction, false significant associations were observed in rectal
cancer (CC vs. TT: BFDP = 0.998; CC vs. (TT + TC): BFDP = 0.998; C vs.
T: BFDP = 0.999) and females (TC vs. TT: BFDP = 0.999). A significantly
increased CRC risk was yielded in overall analysis, Caucasians, Europe
countries populations, and males for CYP1A1 A2455G polymorphism. After
BFDP correction, associations still be significant only in Europe
countries populations (AG vs. AA: BFDP = 0.680; (AG + GG) vs. AA: BFDP =
0.475; G vs. A: BFDP = 0.126). However, when we further performed a
sensitivity analysis and BFDP test, false significant associations were
observed in all analyses (BFDP > 0.8). Conclusions: In
summary, this study suggests that these positive findings may result
from false-positive results, rather than from true associations or
biological factors.