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Cornelia M Ulrich

Publications and source records attributed to Cornelia M Ulrich.

66 records · Page 4Linked to original sources
PubMed2003

5,10-Methylenetetrahydrofolate reductase polymorphisms and leukemia risk: a HuGE minireview.

Leukemias commonly arise as a result of DNA translocations, inversions, or deletions in genes regulating blood cell development or homeostasis. Folate deficiency has been associated with uracil misincorporation into DNA and DNA double strand breaks during uracil excision repair, thus increasing the risk of chromosomal aberrations. Methylenetetrahydrofolate reductase (MTHFR) directs 5,10-methylenetetrahydrofolate toward methionine synthesis at the expense of DNA synthesis. Two MTHFR polymorphisms, C677T and A1298C, have been associated with reduced enzyme activity and C677T with altered distribution of intracellular folate metabolites. Rapidly replicating cell types, such as hematopoietic cells, may be especially sensitive to changes in the availability of intracellular folate. Three case-control studies have evaluated the association between MTHFR polymorphisms and the risk of acute leukemia, and they suggest that both adults and children with the variant forms of MTHFR have a decreased risk of lymphoid leukemias. However, no modification in risk has been observed for myeloid leukemias, suggesting that differences in folate requirements or susceptibility to chromosomal damage may exist between myeloid and lymphoid cells. Further investigation into the association between MTHFR polymorphisms and the risk of leukemia is warranted. It should include larger sample sizes and other polymorphisms in folate metabolism and address interactions with folate status.

Adolescent↗
PubMed2003

Effect of exercise on total and intra-abdominal body fat in postmenopausal women: a randomized controlled trial.

CONTEXT: The increasing prevalence of obesity is a major public health concern. Physical activity may promote weight and body fat loss. OBJECTIVE: To examine the effects of exercise on total and intra-abdominal body fat overall and by level of exercise. DESIGN: Randomized controlled trial conducted from 1997 to 2001. SETTING AND PARTICIPANTS: A total of 173 sedentary, overweight (body mass index > or =24.0 and >33% body fat), postmenopausal women aged 50 to 75 years who were living in the Seattle, Wash, area. INTERVENTION: Participants were randomly assigned to an intervention consisting of exercise facility and home-based moderate-intensity exercise (n = 87) or a stretching control group (n = 86). MAIN OUTCOME MEASURE: Changes in body weight and waist and hip circumferences at 3 and 12 months; total body, intra-abdominal, and subcutaneous abdominal fat at 12 months. RESULTS: Twelve-month data were available for 168 women. Women in the exercise group participated in moderate-intensity sports/recreational activity for a mean (SD) of 3.5 (1.2) d/wk for 176 (91) min/wk. Walking was the most frequently reported activity. Exercisers showed statistically significant differences from controls in baseline to 12-month changes in body weight (-1.4 kg; 95% confidence interval [CI], -2.5 to -0.3 kg), total body fat (-1.0%; 95% CI, -1.6% to -0.4%), intra-abdominal fat (-8.6 g/cm2; 95% CI, -17.8 to 0.9 g/cm2), and subcutaneous abdominal fat (-28.8 g/cm2); 95% CI, -47.5 to -10.0 g/cm2). A significant dose response for greater body fat loss was observed with increasing duration of exercise. CONCLUSIONS: Regular exercise such as brisk walking results in reduced body weight and body fat among overweight and obese postmenopausal women.

Abdomen↗
PubMed2002

Thymidylate synthase promoter polymorphism, interaction with folate intake, and risk of colorectal adenomas.

Thymidylate synthase (TS) is a key enzyme in folate metabolism and the primary target of 5-fluorouracil. A repeat polymorphism in the TS promoter enhancer region (2rpt versus 3rpt of 28 bp) is associated with decreased expression, and a 6-bp deletion in the 3'untranslated region may affect RNA stability. We investigated the role of TS polymorphisms in a case control study of adenomatous polyps (510 cases and 604 polyp-free controls). Multivariate-adjusted odds ratios (ORs; 95% confidence interval) for TSER 2rpt/3rpt and 2rpt/2rpt compared with 3rpt/3rpt were 0.8 (0.6-1.2) and 0.9 (0.6-1.3), respectively. We observed a significant gene-nutrient interaction between the TSER polymorphism and folate intake: among 3rpt/3rpt individuals (greater expression), folate intake > 440 microg/day (highest tertile) versus < or =440 microg/day was associated with a 2-fold decreased risk [ORs 1.0 (reference group) versus 0.5 (0.3-0.9)]. However, among 2rpt/2rpt individuals, high folate intake was associated with a 1.5-fold increased risk [ORs 0.6 (0.4-0.9) versus 0.9 (0.5-1.5; P for interaction = 0.03)]. Vitamin B(12) showed a similar trend (P = 0.08). No clear pattern was seen with the TS 1494del6 polymorphism. These findings raise questions regarding the molecular pathways linking folate metabolism and colorectal carcinogenesis, including whether high folate is beneficial in the presence of all metabolic genotypes.

Adenoma↗
PubMed2002

Cyclooxygenase 1 (COX1) polymorphisms in African-American and Caucasian populations.

Cyclooxygenases (COXs) are the primary targets of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), and thus enzymes of major interest to pharmacology, pharmacogenetics, and epidemiology. Genetic variants that affect enzyme function, or the interaction with NSAIDs, could alter drug response. We have screened the human COX1 gene coding regions of 48 African-American and 47 Caucasian individuals using DNA sequencing. We identified 13 coding-region variants, of which seven were amino-acid substitutions, and further five intronic polymorphisms within 60bp of an exon. All nonsynonymous variants were confirmed in an independent Caucasian population (n=94 unrelated individuals). Most of the discovered polymorphisms were rare, although some variants resulting in amino-acid changes occurred at appreciable frequency in at least one population (> or =4%: R8W, P17L, L237M). We used two sequence-homology-based software programs to predict the potential impact of these polymorphisms on COX1 function. The L237M substitution was predicted as most likely to alter protein function, whereas the glycine at position 230 may be specific to COX1 function. More detailed phenotypic characterizations of these COX1 polymorphisms remain to be undertaken.

Amino Acid Substitution↗
PubMed2002

Pharmacogenetics and folate metabolism -- a promising direction.

Folate metabolism is the target of two major drug groups: folate antagonists (e.g., methotrexate) and thymidylate synthase inhibitors (for example, 5-fluorouracil). These agents are widely used in cancer chemotherapy, as treatment for rheumatoid arthritis, and for other conditions. The administration of these drugs in cancer chemotherapy can induce a state of acute folate depletion with sometimes life-threatening toxic sequelae. Recent studies suggest that polymorphisms in folate-metabolizing enzymes may modify the therapeutic effectiveness and toxicity of drugs targeting folate metabolism. This review briefly summarizes major drugs targeting the folate pathway and describes common polymorphisms in folate-metabolizing enzymes and transport proteins. Pharmacogenetic studies investigating the relevance of these polymorphisms with respect to patients' response to antifolate chemotherapeutic agents are discussed. Investigating genetic variability in folate metabolism in the framework of pharmacogenetics is a promising field. Findings to date illustrate the potential for targeting therapy based on patients' genotypes with improved outcomes and reduced toxicity.

Animals↗
PubMed2002

Mailing strategies and recruitment into an intervention trial of the exercise effect on breast cancer biomarkers.

Recruitment into public health intervention trials can be costly and time-consuming. We examined two components of recruitment for an exercise trial: (a) a randomized pilot study of mailing strategies; and (b) the results from the entire recruitment process. In the pilot study, 4,999 women were randomized into one of four groups using a factorial design. The first factor was the inclusion or exclusion of a personal invitation letter, and the second was the use of first-class stamps versus bulk mail. We received 580 (11.6%) responses. Responses from interested women were nonsignificantly higher (odds ratio, 1.19; P = 0.10) for first-class versus bulk-rate postage. However, the cost to randomize one participant using first-class mail was $56.14 (in 1998 dollars) more than for bulk mail. We found no difference in response when including the invitation letter (odds ratio, 1.00; P > 0.50). The general recruitment process identified potentially eligible women primarily through mass mailings but also through media and other sources. We mailed recruitment materials, via bulk mail and including an invitation letter, to 103,577 women in the Seattle area over 2 years. Response rates were different (P < 0.001) between age groups: 6.2% for 50-59-year-old women; 7.9% for 60-69-year-old women; and 7.4% for 70-75-year-old women. The proportion of respondents eventually randomized did not differ by recruitment strategy (mail, media, other). Our study indicates that bulk mail may be more cost-effective than first-class mail for recruitment into intervention trials and that older women are willing to participate in such studies.

Age Factors↗
PubMed2002

Risk factors for hyperplastic and adenomatous polyps: evidence for malignant potential?

Recent studies have suggested that hyperplastic polyps may be benign precursor lesions for a distinct subset of colorectal tumors. We conducted a clinic-based case-control study to evaluate risk factors for hyperplastic polyps. Cases with hyperplastic polyps (n = 219), adenomas (n = 437), and both types of polyps (n = 138), along with colonoscopy-negative controls (n = 708), were identified at a gastroenterology practice in the Minneapolis area during 1991-1994. A self-administered questionnaire was used to collect risk factor information. Risk factors for hyperplastic and adenomatous polyps were generally similar to those for colorectal cancer. Male sex, smoking, and alcohol consumption were associated with increased risk of all polyp groups; nonsteroidal anti-inflammatory drug use, hormone replacement therapy use, and calcium intake were associated with reduced risk. There was no apparent association between increasing age and hyperplastic polyp risk (P = 0.21) in this analysis, although it was a strong risk factor for adenoma (P < 0.001). The odds ratio (OR) for hyperplastic polyps associated with >25 pack-years of smoking was 4.1 [95% confidence interval (CI), 2.2-7.6], whereas the OR for adenoma alone was 1.3 (95% CI, 0.8-2.3). The OR estimate for individuals diagnosed with both polyp types was 4.2 (95% CI, 1.9-9.3). These results suggest, as one possibility, that the consistent association of adenoma and smoking observed in previous studies may be partially attributable to the inclusion of individuals with both adenomas and hyperplastic polyps in the adenoma case group. To the contrary, individuals with both polyp types may be expressing a phenotype distinct from those who have only adenomas and should be considered separately. Further studies are necessary to establish which polyp phenotypes are related to smoking. Overall, the similarity of the risk profiles of colorectal hyperplastic polyps, adenoma, and cancer provides additional support for the growing body of evidence that some hyperplastic polyps may have neoplastic potential.

Adenomatous Polyps↗
PubMed2002

Polymorphisms in DNA repair genes and associations with cancer risk.

Common polymorphisms in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. To establish our overall understanding of possible in vivo relationships between DNA repair polymorphisms and the development of cancer, we performed a literature review of epidemiological studies that assessed associations between such polymorphisms and risk of cancer. Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez). These studies focused on adult glioma, bladder cancer, breast cancer, esophageal cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma), squamous cell carcinoma of the head and neck, and stomach cancer. We found that a small proportion of the published studies were large and population-based. Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer. Suggestive results were seen for polymorphisms in other genes; however, small sample sizes may have contributed to false-positive or false-negative findings. We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.

DNA Repair↗
PubMedDate not supplied

Effect of a yearlong, moderate-intensity exercise intervention on the occurrence and severity of menopause symptoms in postmenopausal women.

OBJECTIVE: To evaluate the effect of moderate-intensity exercise on the occurrence and severity of menopause symptoms. DESIGN: A yearlong, randomized, clinical trial, conducted in Seattle, WA, with 173 overweight, postmenopausal women not taking hormone therapy in the previous 6 months. The intervention was a moderate-intensity exercise intervention (n = 87) versus stretching control group (n = 86). Using logistic regression, odds ratios comparing exercise with controls were calculated at 3, 6, 9, and 12 months for menopause symptoms and their severity. RESULTS: There was a significant increase in hot flash severity and decreased risk of memory problems in exercisers versus controls over 12 months, although the numbers affected were small. No other significant changes in symptoms were observed. CONCLUSIONS: Exercise does not seem to decrease the risk of having menopause symptoms in overweight, postmenopausal women not taking hormone therapy and may increase the severity of some symptoms in a small number of women.

Adipose Tissue↗
PubMedDate not supplied

Managed care and primary physician satisfaction.

BACKGROUND: We examined whether physician compensation, financial incentives, and care management tools were associated with primary physician job and referral satisfaction. Our study was guided by a conceptual model of physician satisfaction derived from published evidence. METHODS: A cross-sectional survey was performed of 495 primary physicians (family practitioners, general practitioners, general internists) in the Seattle metropolitan area in 1997. RESULTS: Bivariate analyses revealed that salary compensation, productivity bonuses, and withholds for referrals were associated with job and referral dissatisfaction. However, after controlling for physician, practice, and office characteristics, only the association between salary payment and job dissatisfaction remained significant. Practice in offices with more physicians had the strongest association with physician job dissatisfaction. CONCLUSIONS: Although managed care features are correlated with physician job and referral dissatisfaction, the source of dissatisfaction may originate from being an employed physician in a large medical group with more physicians, which may be more likely to impose bureaucratic controls that limit physician autonomy.

Attitude of Health Personnel↗