2-Hydroxylated metabolites of estrogen have been shown to have antiangiogenic effects and inhibit tumor cell proliferation, whereas 4-hydroxylated metabolites have been implicated in carcinogenesis. We examined whether polymorphisms in certain genes involved in estrogen metabolism are associated with endometrial cancer risk in a populationbased case-control study with 371 cases and 420 controls. Based on previously published genotype-phenotype correlation studies, we defined variant alleles thought to increase estrogen 2-hydroxylation as presumptively low-risk (CYP1A1 m1 T6235C and m2 Ile 462 Val) and those thought to increase estrogen 4-hydroxylation as high-risk (CYP1A1 m4 Thr 461 Asn, CYP1A2 A734C, and CYP1B1 Leu 432 Val). Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression. Carrying at least one CYP1A1 m1 or m2 variant allele was associated with a decreased risk of endometrial cancer [ORs (95% CIs), 0.64 (0.44-0.93) and 0.54 (0.30-0.99), respectively]. No strong alteration in risk was observed among women with any of the putative high-risk alleles. When CYP1A1, CYP1A2, and CYP1B1 genotypes were combined and ranked by the number of putative low-risk genotypes carried, women with four or five low-risk genotypes had a reduced risk of endometrial cancer (OR, 0.29; 95% CI, 0.15-0.56) compared with women with one or none. No appreciable alteration in risk was observed among women carrying two or three low-risk genotypes. Some of our findings are consistent with the hypothesis that increased estrogen 2-hydroxylation is associated with decreased endometrial cancer risk, but replication of these results is required before any firm conclusions can be reached.

Clinical isolates of the opportunistic pathogen Mycobacterium avium complex (MAC) undergo a reversible switch between red and white colony morphotypes on agar plates containing the lipoprotein stain Congo red. Compared to their isogenic red counterparts, white morphotypic variants are more virulent and more resistant to multiple antibiotics. This report shows that the two-component regulatory system mtrAB is required for the red-to-white switch as well as for other morphotypic switches of MAC. A mutant with a transposon insertion in the histidine protein kinase gene mtrB was isolated from a morphotypically white parent clone. The mutant resembled a naturally occurring red morphotypic variant in that it stained with Congo red, was sensitive to multiple antibiotics, and was permeable by a fluorescent DNA stain. However, it differed from a red variant in that it could not switch to the white or transparent morphotype, and it could not survive intracellularly within macrophage-like cells. Transcomplementation with a cloned wild-type mtrB gene restored to the mutant the ability to form impermeable, drug-resistant white and transparent variants. Quantitative reverse transcriptase PCR showed that mtrB was required for the normal expression of cell surface Mce proteins, some of which are up-regulated in the red-to-white switch. The results indicate that mtrAB functions in regulating the composition and permeability of mycobacterial cell walls and plays a role in the reversible colony type switches of MAC.The Mycobacterium avium complex (MAC) is the most significant of the environmental mycobacteria that opportunistically infect susceptible humans, especially AIDS patients. MAC infections are difficult to treat due to the intrinsic multidrug resistance of the organism. Drugs such as clarithromycin, azithromycin, rifabutin, ethambutol, amikacin, clofazamine, and fluoroquinolones, which are effective against primary isolates, frequently lose effectiveness unless administered in combination.The intrinsic multidrug resistance of MAC is ascribed to cell wall impermeability, although additional factors are likely to contribute (1,10,11,16,24). Conditions that compromise cell wall integrity result in increased drug susceptibility (10,17,21,26). Intrinsic multidrug resistance might involve nonspecific permeability barriers that decrease drug uptake, possibly working in synergy with more specific efflux mechanisms.There is a correlation between drug susceptibility and colony type of MAC. Virtually all isolates of MAC form multiple colony morphotypes that vary with regard to infectivity and drug susceptibility. The conservation of this property within the species suggests that it confers selective advantages. The opaque-transparent switch is one such switch (1, 25, 33). Transparent variants are more resistant to multiple antibiotics than their opaque counterparts. They also predominate in patient samples and grow better in animal and macrophage models of infection. Opaque variants grow better on laboratory media and predominate af...

Repetitive-sequence-based PCR (rep-PCR