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Regina G Ziegler

Publications and source records attributed to Regina G Ziegler.

At least 19 recordsLinked to original sources

Serum concentrations of estrogens, sex hormone-binding globulin, and androgens and risk of breast cancer in postmenopausal women.

We assessed the relationship between serum concentrations of estrogens, androgens, and sex hormone-binding globulin and risk of breast cancer among postmenopausal women. Study participants provided serum prior to breast biopsy or mastectomy in 3 hospitals in Grand Rapids, Michigan between 1977 and 1987. A total of 179 subjects with localized breast cancer were compared to 152 subjects with nonproliferative breast changes that have not been associated with elevated breast cancer risk. Increasing serum concentrations of estrone and estrone sulfate were associated with increases in breast cancer risk; the odds ratios (ORs) in the fourth quartiles compared to the first were 2.3 (95% confidence interval (CI) 1.1-4.6) for both (p-trend = 0.02 and 0.03, respectively). Estradiol and bioavailable estradiol concentrations were associated with nonstatistically significant increases in risk. Androstenediol levels were associated with risk (p-trend = 0.01); the OR in the fourth compared to the first quartile was 2.2 (95% CI 1.0-4.6). Testosterone, dehydroepiandrosterone and androstenedione levels were not associated with increased risk. Sex hormone-binding globulin was associated with a nonsignificant decrease in risk. Associations with estrone and estrone sulfate persisted after adjustment for androstenediol (ORs for fourth compared to first quartiles were 2.0 (95% CI 0.9-4.5) and 2.2 (95% CI 1.0-4.6), respectively (p-trend = 0.16 for both). The association with androstenediol was attenuated after adjustment for estrone (OR for fourth compared to first quartile was 1.6 (95% CI 0.7-3.6); p-trend = 0.13). Higher serum concentrations of estrogens were associated with increased breast cancer risk in postmenopausal women. Androgen levels were not independently associated with substantially increased risk.

Aged↗

Analysis of fifteen estrogen metabolites using packed column supercritical fluid chromatography-mass spectrometry.

Packed column supercritical fluid chromatography with tandem mass spectrometry was used for the separation of estrone, estradiol, estriol, 16-epiestriol, 17-epiestriol, 16-ketoestradiol, 16alpha-hydroxyestrone, 2-methoxyestrone, 4-methoxyestrone, 2-hydroxyestrone-3-methyl ether, 2-methoxyestradiol, 4-methoxyestradiol, 2-hydroxyestrone, 4-hydroxyestrone, and 2-hydroxyestradiol. A gradient of methanol in carbon dioxide (0-30% methanol in 15 min, 2% change/min) at a flow rate of 2 mL/min and cyanopropyl silica column connected in series with a diol column, both 2.1 mm i.d. x 150 mm long, packed with 5-mum spherical silica-based particles, resulted in the separation and quantification of all 15 estrogens in less than 10 min. The limit of detection (LOD) and limit of quantitation (LOQ) of this pSFC MS/MS method was determined to be 0.5 (S/N = 3), and 5 pg, respectively. Compared with RP-HPLC MS analysis of the same mixture in terms of speed of analysis and sensitivity, pSFC MS is much faster, 10 versus 70 min, with comparable LOD and LOQ.

Carbon Dioxide↗

Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: Several epidemiologic studies suggest that higher folate intakes are associated with lower breast cancer risk, particularly in women with moderate alcohol consumption. OBJECTIVE: We investigated the association between dietary folate, alcohol consumption, and postmenopausal breast cancer in women from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort. DESIGN: Dietary data were collected at study enrollment between 1993 and 2001. Folate content was assigned on the basis of prefortification (ie, pre-1998) databases. Of the 25 400 women participants with a baseline age of 55-74 y and with complete dietary and multivitamin information, 691 developed breast cancer between September 1993 and May 2003. We used Cox proportional hazard models with age as the underlying time metric to generate hazard ratios (HRs) and 95% CIs. RESULTS: The adjusted HRs were 1.19 (95% CI: 1.01, 1.41; P for trend = 0.04) for women reporting supplemental folic acid intake >/=400 mug/d compared with subjects reporting no supplemental intake. Comparison of the highest with the lowest quintile gave adjusted HRs of 1.04 (95% CI: 0.83, 1.31; P for trend = 0.56) and 1.32 (95% CI: 1.04, 1.68; P for trend = 0.03) for food and total folate intake, respectively. Alcohol consumption was positively associated with breast cancer risk (highest compared with lowest quintile: HR = 1.37; 95% CI: 1.08, 1.76; P for trend = 0.02); the risk was greatest in women with lower total folate intake. CONCLUSIONS: Our results do not support the hypothesis that high folate intake reduces breast cancer risk; instead, they suggest that a high intake, generally attributable to supplemental folic acid, may increase the risk in postmenopausal women. However, our results confirm previous studies showing positive associations between moderate alcohol consumption and breast cancer.

Aged↗

Association of energy intake and energy balance with postmenopausal breast cancer in the prostate, lung, colorectal, and ovarian cancer screening trial.

Energy restriction remains one of the most effective ways known to prevent breast cancer in animal models. However, energy intake has not been consistently associated with risk of breast cancer in humans. In a prospective study, we assessed whether energy intake, body size, and physical activity each independently influence breast cancer risk in postmenopausal women and estimated the joint effect of combinations of these individual factors. As part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 38,660 women, ages 55 to 74 years and recruited from 10 centers in the United States during 1993 to 2001, were randomized to the screening arm of the trial. At baseline, the women completed a self-administered questionnaire, including a food frequency questionnaire. During follow-up from 1993 to 2003, 764 incident breast cancer cases were ascertained. Women in the highest quartile of energy intake (> or = 2,084 kcal/d) compared with those in the lowest quartile (<1,316 kcal/d) had a significantly increased risk for breast cancer [multivariate relative risk (RR), 1.25; 95% confidence interval (95% CI), 1.02-1.53; P(trend continuous) = 0.03]. Current body mass index (BMI) was also positively and significantly associated with risk (multivariate RR comparing >30 kg/m2 with <22.5 kg/m2, 1.35; 95% CI, 1.06-1.70; P(trend) = 0.01). Women with > or = 4 hours/wk of vigorous recreational physical activity had a significantly reduced risk of breast cancer compared with those who reported no recreational physical activity (multivariate RR, 0.78; 95% CI, 0.60-0.99; P(trend) = 0.15). None of these associations with individual energy balance measures was substantially confounded by the other two measures. When we estimated the joint effect of all three variables, women with the most unfavorable energy balance (the highest energy intake, highest BMI, and least physical activity) had twice the risk (RR, 2.10; 95% CI, 1.27-3.45) of women with the most favorable energy balance (the lowest energy intake, lowest BMI, and most physical activity). Although our estimates of absolute energy intake, based on a food frequency questionnaire, are imperfect, these results suggest that energy intake, in addition to BMI and physical activity may be independently associated with breast cancer risk. In addition, these three aspects of energy balance may act jointly in determining breast cancer risk.

Aged↗

Measuring fifteen endogenous estrogens simultaneously in human urine by high-performance liquid chromatography-mass spectrometry.

A sensitive, specific, accurate, and precise high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method for measuring the absolute quantities of 15 endogenous estrogens and their metabolites in human urine has been developed and validated. The method requires a single hydrolysis/extraction/derivatization step and only 0.5 mL of urine, yet is capable of simultaneously quantifying estrone and its 2-, 4-methoxy and 2-, 4-, and 16alpha-hydroxy derivatives, and 2-hydroxyestrone-3-methyl ether; estradiol and its 2-, 4-methoxy and 2-, 16alpha-hydroxy derivatives, 16-epiestriol, 17-epiestriol, and 16-ketoestradiol in pre- and postmenopausal women as well as men. Standard curves are linear over a 10(3)-fold concentration range with the standard error of the estimate (SEE) and the relative standard error of the estimate (RSEE) for the linear regression line ranging from 0.0131 to 0.1760 and 1.2 to 7.3%, respectively. The lower limit of quantitation for each estrogen is 0.02 ng/0.5 mL urine sample (2 pg on column), with the percent recovery of a known added amount of compound (accuracy) of 96-107% and an overall precision, including the hydrolysis, extraction, and derivatization steps, of 1-5% relative standard deviation (RSD) for samples prepared concurrently and 1-12% RSD for samples prepared in separate batches. Since individual patterns of estrogen metabolism may influence the risk of breast cancer, accurate, precise, and specific measurement of endogenous estrogen metabolites in biological matrixes will facilitate future research on breast cancer prevention, screening, and treatment.

Adult↗

Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort.

BACKGROUND: Dairy intake may increase prostate cancer risk, but whether this is due to calcium's suppression of circulating vitamin D remains unclear. Findings on calcium and vitamin D intake and prostate cancer are inconsistent. OBJECTIVE: We examined the association of dairy, calcium, and vitamin D intake with prostate cancer. DESIGN: In a prospective study of 3612 men followed from 1982-1984 to 1992 for the first National Health and Nutrition Examination Epidemiologic Follow-up Study, 131 prostate cancer cases were identified. Dietary intake was estimated from questionnaires completed in 1982-1984. Relative risk (RR) and 95% CIs were estimated by using Cox proportional hazards models adjusted for age, race, and other covariates. RESULTS: Compared with men in the lowest tertile for dairy food intake, men in the highest tertile had a relative risk (RR) of 2.2 (95% CI: 1.2, 3.9; trend P = 0.05). Low-fat milk was associated with increased risk (RR = 1.5; 95% CI: 1.1, 2.2; third compared with first tertile; trend P = 0.02), but whole milk was not (RR = 0.8; 95% CI: 0.5, 1.3; third compared with first tertile; trend P = 0.35). Dietary calcium was also strongly associated with increased risk (RR = 2.2; 95% CI: 1.4, 3.5; third compared with first tertile; trend P = 0.001). After adjustment for calcium intake, neither vitamin D nor phosphorus was clearly associated with risk. CONCLUSIONS: Dairy consumption may increase prostate cancer risk through a calcium-related pathway. Calcium and low-fat milk have been promoted to reduce risk of osteoporosis and colon cancer. Therefore, the mechanisms by which dairy and calcium might increase prostate cancer risk should be clarified and confirmed.

Calcium, Dietary↗

Serum concentrations of estrogens, sex hormone binding globulin, and androgens and risk of breast hyperplasia in postmenopausal women.

OBJECTIVE: We sought to determine whether serum concentrations of estrogens, androgens, and sex hormone binding globulin in postmenopausal women were related to the presence of mammary hyperplasia, an established breast cancer risk factor. METHODS: Study participants provided serum before breast biopsy or mastectomy in three hospitals in Grand Rapids, Michigan, between 1977 and 1987. A total of 179 subjects with breast hyperplasia were compared with 152 subjects with nonproliferative breast changes that are not associated with increased breast cancer risk. RESULTS: The odds ratios (OR) associated with the three upper quartiles of estradiol in comparison with the lowest quartile were 2.2 [95% confidence interval (95% CI) 1.1-4.6], 2.5 (95% CI, 1.1-5.3), and 4.1 (95% CI, 2.0-8.5; Ptrend = 0.007). The corresponding ORs for bioavailable estradiol, estrone, and estrone sulfate were of generally similar magnitude (Ptrend = 0.003 for bioavailable estradiol, 0.0004 for estrone, and 0.0009 for estrone sulfate). Relative to women concurrently in the lowest tertile for serum estradiol, estrone, and estrone sulfate, women concurrently in the highest tertile for all three hormones had an OR of 5.8 (95% CI, 2.2-15.2). Serum concentrations of sex hormone binding globulin, testosterone, dehydroepiandrosterone, androstenedione, and androstenediol were not associated with risk of hyperplasia. CONCLUSIONS: Serum concentrations of estrogens, but not of androgens or sex hormone binding globulin, were strongly and significantly associated with risk of breast hyperplasia in postmenopausal women, suggesting that estrogens are important early in the pathologic process towards breast cancer.

Androgens↗

Urinary estrogen metabolites and their ratio among Asian American women.

Controversy persists regarding the role of a low ratio of 2-hydroxyestone (2-OHE(1))/16alpha-hydroxyestrone (16alpha-OHE(1)) as a potential estrogen metabolism marker of increased risk for breast cancer. Most of the evidence has been provided by case-control studies, where tumor effects on hormone metabolism are not known. Studies in populations at various risk of breast cancer are not consistent, with some suggesting that levels of the ratio may be altered by changes in diet and exercise. We studied Asian American women participating as controls in a case-control study of breast cancer in which migration history--a composite of the subject's place of birth, type of residence in Asia (urban or rural), length of time living in the West, and grandparents' place of birth--was associated with a 6-fold risk gradient that paralleled the historical differences in incidence rates between the United States and Asian countries. This population offered the possibility to address whether the ratio of 2-OHE(1):16alpha-OHE(1) differs according to recognized breast cancer risk factors, including migration history. Overnight 12-hour urines were obtained from 368 premenopausal and 143 naturally postmenopausal women of Chinese, Japanese, or Filipino descent who donated urines between 1985 and 1988. The estrogen metabolites 2-OHE(1) and 16alpha-OHE(1) were measured with an ELISA kit and adjusted for creatinine levels. In each ethnic group, the ratio of 2-OHE(1):16alpha-OHE(1) was consistently lower in women born in the West than in those who had migrated from Asia. For premenopausal women, the ratio declined 20% due to lower levels of 2-OHE(1). Among postmenopausal women, the ratio was 23% lower in those born in the West, but no consistent patterns based on place of birth were observed for either 2-OHE(1) or 16alpha-OHE(1). The ratio did not vary with most recognized breast cancer risk factors, except for lower metabolite ratios in women with a younger age at first birth and more children, which runs contrary to the hypothesis, because both characteristics reduce breast cancer risk. Our study suggests that the ratio of 2-OHE(1):16alpha-OHE(1) may be a marker for lifestyle influences on estrogen metabolism associated with westernization.

Adult↗

Measuring seven endogenous ketolic estrogens simultaneously in human urine by high-performance liquid chromatography-mass spectrometry.

A rapid, sensitive, and specific high-performance liquid chromatography-electrospray ionization-multistage mass spectrometry (MS) method for measuring endogenous ketolic estrogen metabolites in human urine has been developed. The method requires a single hydrolysis/extraction/derivatization step and only 2.5 mL of urine, yet is able to simultaneously quantify estrone and its 2-methoxy and 2-, 4-, and 16alpha-hydroxy derivatives, 16-ketoestradiol, and 2-hydroxyestrone-3-methyl ether metabolites. The combination of a simple hydrazone derivatization step with multistage MS greatly enhances the sensitivity and specificity of the analysis of endogenous estrogen within human urine. Standard curves are linear over a 100-fold concentration range with linear regression correlation coefficients typically greater than 0.99. The lower limit of quantitation for each ketolic estrogen is 0.2 ng/2.5-mL urine sample (10 pg on column), with an accuracy of 93-103% and an overall precision, including the hydrolysis, extraction, and derivatization steps, of 1-13% relative standard derivation (RSD) for samples prepared concurrently and 8-16% RSD for samples prepared in separate batches. This method also allows for the identification of 2-hydroxyestrone-3-methyl ether in urine obtained from both pre- and postmenopausal women. This potentially protective estrogen metabolite has been previously reported only in the urine of pregnant women. Since individual patterns of estrogen metabolism may influence the risk of breast cancer, accurate and specific measurement of estrogen metabolites in biological matrixes will facilitate future research on breast cancer prevention, screening, and treatment.

Adult↗

Serum concentrations of IGF-I, IGFBP-3 and c-peptide and risk of hyperplasia and cancer of the breast in postmenopausal women.

Experimental evidence suggests that insulin and insulin-related growth factors may play a role in breast pathology through their mitogenic and anti-apoptotic effects on breast cells. Our objective was to assess the relationship between serum concentrations of insulin-like growth factor-I (IGF-I), its major binding protein (IGFBP-3), the ratio IGF-I:IGFBP-3, c-peptide (a marker of insulin secretion) and the ratio c-peptide:fructosamine (a marker of insulin resistance) and the risk of epithelial hyperplasia (an established breast cancer risk factor) and localized breast cancer among postmenopausal women. Study subjects were patients who provided serum before breast biopsy or mastectomy in 3 hospitals in Grand Rapids, MI between 1977 and 1987. Two case groups, 186 subjects with epithelial hyperplasia of the breast and 185 subjects with localized breast cancer, were compared to 159 subjects with nonproliferative breast changes that have not been associated with increased breast cancer risk. Serum concentrations of IGF-I, IGFBP-3 and the ratio IGF-I:IGFBP-3 were not related to risk of either hyperplasia or breast cancer. For women in the highest quartile of c-peptide or of c-peptide:fructosamine compared to those in the lowest quartile, the odds ratios (ORs) for hyperplasia were 3.0 (95% confidence interval [CI] 1.4-6.5) and 3.3 (95% CI 1.5-7.3), respectively (p trend = 0.02 and 0.02, respectively). The corresponding ORs for breast cancer were 1.5 (95% CI 0.7-3.0) and 1.6 (95% CI 0.8-3.2), respectively (p trend = 0.35 and 0.25, respectively). Our results suggest that insulin and insulin resistance may play a role in breast pathology in postmenopausal women.

Adult↗

Dietary patterns and prostate cancer risk in the National Health and Nutrition Examination Survey Epidemiological Follow-up Study cohort.

Ecological studies implicate a "Western" diet in prostate cancer development, but whether dietary patterns measured in individuals are associated with risk has not been studied previously. We examined this issue using prospective data from the nationally representative United States Health Examination Epidemiological Follow-up Study. Among 3,779 men followed from 1982-84 to 1992, 136 incident cases were identified. Using principal component analysis on responses to a 105-item dietary questionnaire, the following three distinct patterns were identified: a vegetable-fruit pattern; a red meat-starch pattern characterized by red meats, potatoes, cheese, salty snacks, and desserts; and a Southern pattern characterized by such foods as cornbread, grits, sweet potatoes, okra, beans, and rice. In adjusted proportional hazards models, prostate cancer risk was not associated with the vegetable-fruit or red meat-starch pattern, but higher intake of the Southern pattern showed a reduction in risk (3rd versus 1st tertile relative risk, 0.6; 95% confidence interval, 0.4-1.1; trend P = 0.08) that approached statistical significance. The inverse association was observed in black and non-black men and was not attributable to intake of any individual foods or nutrients. A Southern dietary pattern may reflect a history of living in the South and serve as an integrative marker of sunlight exposure and protection through 1,25-dihydroxyvitamin D production. Further evaluation and better characterization of the pattern would offer more information on potentially beneficial features of the diet or its associated lifestyle.

Diet↗

A case-control study of risk factors for invasive cervical cancer among U.S. women exposed to oncogenic types of human papillomavirus.

Oncogenic human papillomavirus (HPV) infections, the necessary cause of most cervical cancers, are common and usually clear within 1 to 2 years. Identifying cofactors that lead to cancer among HPV-infected women has depended mainly on case-control studies defining HPV by DNA testing. DNA testing assesses only current infection; thus, concerns about residual confounding remain. To assess cofactors, we used seropositivity to five oncogenic HPV types as a marker of past exposure and confined our analysis to seropositive controls compared with cancer cases. Study subjects had participated in a multicenter U.S. case-control study conducted in the early 1980s. The detailed questionnaire and stored sera for 235 cases of squamous carcinoma and 486 controls motivated the reanalysis. We measured antibodies to HPV types 16, 18, 31, 45, and 52. Independent, significant predictors of seropositivity among controls included numbers of sexual partners, Black race, and oral contraceptive use. Condom use was protective. Among HPV-exposed women, Papanicolaou screening, Black race, and yeast infection were significantly associated with reduced cancer risk. Current smoking was associated with a 2-fold increase in risk; there were independent, significant trends of increased risk with numbers of cigarettes smoked (P for trend = 0.003) and years of smoking (P for trend = 0.01). Other significant predictors of increased risk included low education and income and history of nonspecific genital infection. Unlike recent HPV DNA-based investigations, based on the use of HPV-seropositive controls in this study, oral contraceptive use was unrelated to the risk of cervical cancer and multiparity was only weakly related to risk. It is particularly worth considering further why studies of different designs are inconsistent regarding the effect of oral contraceptive use.

Adult↗

Dietary fibre and colorectal adenoma in a colorectal cancer early detection programme.

BACKGROUND: Although dietary fibre has been reported to have no association with colorectal adenoma and cancer, in some studies this topic remains controversial. METHODS: We used a 137-item food frequency questionnaire to assess the relation of fibre intake and frequency of colorectal adenoma. The study was done within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomised controlled trial designed to investigate methods for early detection of cancer. In our analysis, we compared fibre intake of 33971 participants who were sigmoidoscopy-negative for polyps, with 3591 cases with at least one histologically verified adenoma in the distal large bowel (ie, descending colon, sigmoid colon, or rectum). Odds ratios were estimated by logistic regression analysis. FINDINGS: High intakes of dietary fibre were associated with a lower risk of colorectal adenoma, after adjustment for potential dietary and non-dietary risk factors. Participants in the highest quintile of dietary fibre intake had a 27% (95% CI 14-38, p(trend)=0.002) lower risk of adenoma than those in the lowest quintile. The inverse association was strongest for fibre from grains and cereals and from fruits. Risks were similar for advanced and non-advanced adenoma. Risk of rectal adenoma was not significantly associated with fibre intake. INTERPRETATION: Dietary fibre, particularly from grains, cereals, and fruits, was associated with decreased risk of distal colon adenoma.

Adenoma↗

Serum selenium and risk of prostate cancer in U.S. blacks and whites.

Prostate cancer is the fourth most common cancer in men worldwide and the most common cancer in men in the United States, with reported incidence rates for U.S. blacks being the highest in the world. The etiology of prostate cancer and an explanation for the racial disparity in incidence in the United States remain elusive. Epidemiologic studies suggest that selenium, an essential trace element, may protect against the disease. To further explore this hypothesis, we measured serum selenium in 212 cases and 233 controls participating in a multicenter, population-based case-control study that included comparable numbers of U.S. black and white men aged 40-79 years. Serum selenium was inversely associated with risk of prostate cancer (comparing highest to lowest quartiles, OR = 0.71, 95% CI 0.39-1.28; p for trend = 0.11), with similar patterns seen in both blacks and whites. Cubic regression spline analysis of continuous serum selenium indicated a reduced risk of prostate cancer above concentrations of 0.135 microg/ml (median among controls) compared to a reference value set at the median of the lowest selenium quartile. Because both the selenoenzyme GPX and vitamin E can function as antioxidants, we also explored their joint effect. Consistent with other studies, the inverse association with selenium was strongest among men with low serum alpha-tocopherol concentrations. In conclusion, our results suggest a moderately reduced risk of prostate cancer at higher serum selenium concentrations, a finding that can now be extended to include U.S. blacks. Since selenium exposure varies widely throughout the world, further research on optimal concentrations for cancer prevention is justified.

Adult↗

Stable isotope dilution high-performance liquid chromatography-electrospray ionization mass spectrometry method for endogenous 2- and 4-hydroxyestrones in human urine.

A sensitive, precise and accurate stable isotope dilution high-performance liquid chromatography-electrospray ionization mass spectrometry method has been developed for measuring endogenous 2- and 4-hydroxyestrones, the main catechol estrogens in human urine. Compared to the published methods using gas chromatography-mass spectrometry, this approach simplifies sample preparation and increases the throughput of analysis. The unique part of our method is the use of a simple and rapid derivatization step that forms a hydrazone at the C-17 carbonyl group of catechol estrogens. This derivatization step has greatly enhanced method sensitivity as well as HPLC separability of 2- and 4-hydroxyestrones. Standard curves were linear over a 100-fold calibration range with correlation coefficients for the linear regression curves typically greater than 0.996. The lower limit of quantitation for each catechol estrogen is 1 ng per 10-ml urine sample, with an accuracy of 97-99% and overall precision, including the hydrolysis, extraction and derivatization steps, of 1-3% for samples prepared concurrently and 2-11% for samples prepared in several batches. This method is adequate for measuring the low endogenous levels of catechol estrogens in urine from postmenopausal women.

Adult↗