Table 1.

Summary of polymorphisms in CYP1A1, CYP1A2, CYP1B1, COMT, GSTM1, and GSTT1 examined in the current study and the expected direction of effect on risk of the presence of the variant allele under the hypothesis that an increased 2:4-hydroxylation ratio decreases risk of endometrial cancer

GenePrimary pathwayAlleleNucleotide changePossible effect of the variant alleleExpected direction of effect on riskReferences*
CYP1A12-Hydroxylation“m1,” MspIT6235C in 3′ noncoding regionIncreased enzyme activity and inducibilityDecrease(24-28)
“m2”Ile462Val in exon 7Increased enzyme activity and inducibilityDecrease(27, 28, 32-34)
“m4”Thr461Asn in exon 7Decreased activityIncrease(36, 38)
CYP1A22-HydroxylationC ValA734C in intron 1Decreased inducibilityIncrease(39, 40)
CYP1B14-HydroxylationLeu432Val in exon 3Higher 4:2-OH estradiol ratioIncrease(42-48)
COMTConverts catechol estrogens to inactive metabolitesMetVal158Met in exon 4Decreased activityIncrease(50, 51)
GSTM1Phase II detoxification“null”Gene deletionNo activityIncrease(53)
GSTT1Phase II detoxification“null”Gene deletionNo activityIncrease(54)
  • * Not all studies observed functional consequences of the polymorphisms studied, including refs. 29-31 for CYP1A1 m1, refs. 26, 35-37 for CYP1A1 m2, ref. 41 for CYP1A2, ref. 49 for CYP1B1, and ref. 52 for COMT.