Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk.

The endogenous metabolism of estrogens is primarily oxidative and involves hydroxylation of the steroid at either C2 (2-OHE1) or C16 (16-OHE1). While the 2-OHE1 metabolites are essentially devoid of peripheral biological activity, 16-OHE1 is an estrogen agonist. There is evidence of an association between the 2-OHE1/16-OHE1 metabolites ratio and breast cancer risk. The CYP1A1 gene may play a role in the 2-hydroxylation (2-OH) of estradiol. African-American women with the wild-type CYP1A1 gene showed a significant increase in the 2-OHE1/16-OHE1 ratio, from 1.35 +/- 0.56 at baseline to 2.39 +/- 0.98 (p = 0.006) after 5 days of treatment with indole-3-carbinol (400 mg/day), a 2-OHE1 inducer. Women with the Msp1 polymorphism showed no significant increase, (0.37% +/- 0.17%). In a case-control study involving 57 women with breast cancer and 312 female controls, the frequency of the homozygous Msp1 polymorphism was 4.2% in African-American controls and 16% in African-American breast cancer cases. The odds ratio of breast cancer with the Msp1 homozygous variant was 8.4 (95% confidence interval: 1.7-41.7). This association was not observed in Caucasian women. The other CYP1A1 polymorphisms were not associated with breast cancer. The CYP1A1 Msp1 polymorphism may be a marker of altered estradiol metabolism and of increased susceptibility to estrogen-related breast cancer in African-Americans.

Accuracy of self-report of breast implants.

The accuracy of self-report of breast implants was analyzed using a random sample of 130 of 850 available records from a retrospective cohort study of women who underwent cosmetic surgical procedures from 1963 to 1985. Women with breast implants correctly reported having the surgery 89.3 percent of the time, whereas women having other cosmetic surgical procedures correctly reported having the index surgery 92.7 percent of the time. Younger age at surgery, younger age at survey response, and higher level of education were significantly associated with higher sensitivity of self-report. Despite high validity of reporting of surgery, accuracy of self-report of time of surgery was low, with only 9 percent of women who reported their breast implant surgery providing the correct month and year of surgery. These results are in contrast with a previous validity study.

Effects of indole-3-carbinol on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in smokers.

Indole-3-carbinol (I3C) is a component of the human diet, occurring as a conjugate in certain cruciferous vegetables. I3C protects against carcinogenesis in a variety of animal models by modifying carcinogen metabolism. In mice, I3C decreases lung tumor formation by the tobacco-specific nitrosamine 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by enhancing its hepatic clearance (M. A. Morse et al., Cancer Res., 50: 2613-2617, 1990). In this study, our goal was to determine whether I3C would have similar effects on NNK metabolism in smokers as it did in mice. Thirteen women took 400 mg of I3C on 5 consecutive days and maintained constant smoking habits during this period. Their urine was analyzed before and after the I3C treatment period for two metabolites of NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc). I3C treatment resulted in decreased levels of urinary NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc, and increased NNAL-Gluc:NNAL ratio in 10 of the 13 women. The mean decreases in NNAL (-0.27 +/- 0.09 pmol/mg creatinine, -23.4%) and NNAL plus NNAL-Gluc (-0.43 +/- 0.16 pmol/mg creatinine, -10.9%) were statistically significant as was the increase in NNAL-Gluc:NNAL ratio (1.1 +/- 0.5, 39.9%). These changes in urinary metabolites of NNK were consistent with those seen in mice treated with I3C and NNK; they suggest that I3C increased hepatic metabolism of NNK in our smokers. This is the first study to examine the effects of I3C on metabolism of an exogenous carcinogen in humans.

Applying management strategies in molecular epidemiology field studies.

In conducting field studies of human exposure, we have encountered significant methodological challenges. The management strategy our group developed to conduct two recent studies of environmental health utilizes a collaborative study design process and innovative protocol management tools, and emphasizes community outreach. We present here the phases of planning, development and realization of two studies--one conducted in an environmentally contaminated area, and another in an occupational setting. We show how the use of this management strategy increases the efficiency of field operations and improves variability assessment.

Temperature variations in upright mechanical freezers.

We examined temperature deviations from the set temperature in specific locations, between-freezer temperature variability, and the effect of defrosting on temperature deviation in a group of 15 upright mechanical freezers, part of a biological sample bank of a large prospective cohort study. By using an Omega Type T Thermocouple Microcomputer thermometer with the freezers set at -80 degrees C, the internal temperature (12 locations in each freezer) ranged from -90 degrees C to -43.5 degrees C. Overall, internal temperatures tended to be appreciably warmer in the upper and front sections of the freezers. Upright front-loading mechanical freezers, which are widely used in research laboratories throughout the world, may not be optimally suited to preserve human biological samples for long-term banking in epidemiology.

The estimated frequency of cosmetic breast augmentation among US women, 1963 through 1988.

Estimates ranging from 1 to 2 million have been used to describe the number of women in the United States who have had cosmetic breast implants. Original data from a historical cohort study of women with breast augmentation were combined with simulation techniques to compute new estimates grounded on a more objective set of information and assumptions than previous attempts. It was estimated that the number of women who had cosmetic augmentation mammoplasty between 1963 and 1988 was 894,206 (range = 437,602 to 2,035,783). The number of women ever treated with cosmetic augmentation mammoplasty may be substantially smaller than previously reported.