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Biomedical subjects

M R Andersen

Publications and source records attributed to M R Andersen.

At least 19 recordsLinked to original sources

Worry about ovarian cancer risk and use of ovarian cancer screening by women at risk for ovarian cancer.

OBJECTIVE: This study examined reports of perceived risk of ovarian cancer, worry, and screening use in a large sample of women. While screening for asymptomatic women is not generally recommended, in 1994 a consensus conference concluded that women with multiple affected relatives are at high risk for ovarian cancer and should be encouraged to participate in screening. The consensus report also suggested that women with a single affected first-degree relative are at elevated risk and while these women were not encouraged to get screening it was suggested that they may choose to pursue screening outside of a randomized trial [NIH Consensus Conference. JAMA 1995;273(6) 491-7]. METHODS: A total of 3257 women participated in this research by completing a mailed survey on ovarian cancer risk, worry, and use of screening. One hundred forty-two of these women were at high risk for this disease due to a strong family history. An additional 144 women were at elevated risk due to a single first-degree affected relative with ovarian cancer. RESULTS: Family history did predict perceived risk, difficulties due to worry, and use of ovarian cancer screening. However, the group of women most likely to report high levels of perceived risk and to have received screening for ovarian cancer were women with a single affected relative rather than those at high risk, for whom screening is recommended. CONCLUSIONS: These results suggest that many women need additional education about ovarian cancer risk. Most women overestimated their risk for this disease. Some average-risk women get screening although it is not recommended outside of randomized trials, and a significant percentage of women at high risk fail to get recommended screening.

Adolescent↗

Variation in the promoter region of the myeloperoxidase gene is not directly related to lung cancer risk among male smokers in Finland.

In order to examine whether a polymorphism in the promoter region of the myeloperoxidase (MPO) gene is associated with lung cancer among male smokers, we conducted a case-control study nested within a Finnish clinical trial cohort. Although we found no evidence of an overall association between lung cancer risk and MPO genotype, the variant MPO genotype was associated with an increased risk of lung cancer among a subset of older men. These findings contrast with those from previous studies that report decreased lung cancer risk among MPO variant individuals.

Age Factors↗

Polymorphisms of the DNA repair gene XRCC1 and lung cancer risk.

We explored the association between polymorphisms of the DNA repair gene XRCC1 (codons 194, 280, and 399) and lung cancer risk in a case-control study nested within a cohort of tin miners. Cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with increased lung cancer risk (odds ratio, 1.8; 95% confidence interval, 1.0-3.4) after adjustment for radon and tobacco exposure. In addition, individuals with the variant Arg280His allele who were alcohol drinkers seemed to be at higher risk for lung cancer compared with those with the homozygous wild-type genotype. Conversely, individuals with the variant Arg194Trp allele who were alcohol drinkers seemed to be at lower risk for lung cancer compared with those with the homozygous wild-type genotype. Polymorphisms of XRCC1 appear to influence risk of lung cancer and may modify risk attributable to environmental exposures.

Adult↗

Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk.

Human cellular glutathione peroxidase 1 (hGPX1) is a selenium-dependent enzyme that participates in the detoxification of hydrogen peroxide and a wide range of organic peroxides. We conducted a case-control study nested within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort to evaluate the association between the proline to leucine polymorphism at codon 198 of hGPX1 and lung cancer risk. Cases (n = 315) were matched to controls on age (+/-5 years), intervention group, and study clinic using incidence density sampling in a 1:1 ratio. The prevalence of the hGPX1 Pro198Leu variant allele was 58% for controls and 71% for cases (P < 0.001). Using conditional logistic regression, we found a significant association between hGPX1 genotype and lung cancer risk. The odds ratio for heterozygotes was 1.8 (95% confidence interval, 1.2-2.8) and 2.3 (95% confidence interval, 1.3-3.8) for homozygous variants compared to wild-type individuals. Due to its high prevalence, the hGPX1 variant may contribute significantly to lung cancer risk among Caucasians but not among ethnic Chinese who do not exhibit this polymorphism.

Age Factors↗

Quality of life in survivors of colorectal carcinoma.

BACKGROUND: Colon carcinoma is a common malignancy that accounts for a substantial share of all cancer-related morbidity and mortality. However, little is known with regard to general and disease specific quality of life in survivors of colorectal carcinoma, particularly from community-based samples of cases across stage and survival times from diagnosis. METHODS: Subjects with colorectal carcinoma were recruited from the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry. Subjects completed two self-administered surveys: the Functional Assessment of Cancer Therapy Scales for Colorectal Cancer (FACT-C) and the Health Utilities Index (HUI) Mark III. RESULTS: One hundred seventy-three respondents (average age: 70.4 years, 71.4% female) completed the survey. In the first 3 years after diagnosis, quality of life was lower and varied substantially among respondents. After 3 years, respondents in all TNM stages of disease except Stage IV reported a relatively uniform and high quality of life. Pain, functional well-being, and social well-being were affected most substantially across all stages and times from diagnosis. Low income status was associated with worse outcomes for pain, ambulation, and social and emotional well-being. Only emotional well-being scores improved significantly over time in both surveys. CONCLUSIONS: Those individuals who achieve a long term remission from colorectal carcinoma may experience a relatively high quality of life, although deficits remain for several areas, particularly in those of low socioeconomic status. Sampling design may have excluded the most severely ill patients.

Activities of Daily Living↗

Genetic counseling for women with an intermediate family history of breast cancer.

Women with a family history of breast cancer often over-estimate their personal risk for cancer and may view themselves as candidates for genetic testing even when the likelihood of an informative test result is low. We report here on genetic counseling of women with an intermediate family history of breast cancer, defined as women who have one or more biological relatives with breast cancer but whose pedigree suggests a low likelihood of autosomal dominant transmission. A genetic counseling protocol based on traditional genetic counseling strategies was developed with additional components added to address the needs of women with moderately increased breast cancer risk. These additional components included information about non-genetic risk factors, comparisons of high and moderate risk pedigrees, and evaluation of personal risk based on both genetic and nongenetic risk factors. Most participants liked the genetic counseling and found it useful. At baseline, participants over-estimated both their personal risk of breast cancer and that of the average woman. After counseling, estimates of personal and average risk of breast cancer were lower, although both remained higher than actual risk. Most participants reported that they felt less worried about breast cancer after receiving their personal-risk estimate. At baseline, most women judged themselves to be candidates for genetic testing and expressed interest in testing. The number who considered themselves candidates for testing was reduced after counseling (60% versus 82%) but still constituted a majority. Similarly, interest in testing was partially reduced by counseling (60% versus 91%). We conclude that genetic counseling can help women with an intermediate family history of breast cancer to develop more accurate views of their risk, reduce their breast cancer worry, and aid some of them in developing a more realistic view of genetic testing.

Adolescent↗

Endothelial nitric oxide synthase activity in aorta of normocholesterolemic rabbits: regional variation and the effect of estrogen.

OBJECTIVE: Several animal studies suggest that nitric oxide (NO) produced by the endothelium attenuates arterial cholesterol accumulation. In the present study we have asked the following questions: (1) is the regional variation in aortic cholesterol accumulation in hypercholesterolemic rabbits preceded by a regional variation in endothelial NO synthase (eNOS) activity in normocholesterolemic rabbits, and (2) is the antiatherogenic effect of estrogen in hypercholesterolemic rabbits preceded by a higher eNOS activity in normocholesterolemic rabbits. METHODS: The eNOS activity was determined by conversion of 14C-L-arginine to 14C-L-citrulline in freshly isolated endothelial cells of aorta in normocholesterolemic rabbits. In the regional variation study, 16 male and eight female rabbits were used. In the estrogen study, ovariectomized female rabbits were subcutaneously injected three times weekly with either 17beta-estradiol (n=7) or vehicle (n=7) for 18 weeks. RESULTS: In the regional variation study, the atherosclerosis prone aortic arch showed a significant lower eNOS activity than the more resistant abdominal aorta in both male (P<0.0001) and female (P<0.05) rabbits. In the estrogen study, the eNOS activity in the aortic arch and upper thoracic aorta was significantly higher in the estrogen than in the vehicle rabbits (P<0.05). In the lower thoracic aorta, however, the eNOS activity was the same. CONCLUSION: The findings suggest that a high NO production in the luminal endothelium of the arterial wall precedes a low cholesterol accumulation during a subsequent period of hypercholesterolemia.

Analysis of Variance↗

Reported ovarian cancer screening among a population-based sample in Washington state.

OBJECTIVE: To assess the prevalence of reported ovarian cancer screening among a population-based sample of women from Washington state and identify factors that influence the decision to be screened. METHODS: A population-based sample of 6749 women aged 54-84 years, living in 40 predominately rural communities in Washington state, was surveyed about their utilization of ultrasonography and CA 125 for ovarian cancer screening. We also assessed relevant demographic, family history, psychosocial, and health behavior variables. RESULTS: After exclusions, data from 4938 respondents were available. Two percent (n = 96) reported having been screened. Multiple logistic regression identified ovarian cancer worry, contact with an obstetrician-gynecologist, and family history of ovarian cancer as independently associated with screening. Based on self-reported family histories, 27 women had pedigrees consistent with high risk of ovarian cancer, but none of those women reported having been screened. CONCLUSION: Ovarian cancer screening is rare. Women at high risk of it might not be getting recommended screening.

Aged↗

The effectiveness of mammography promotion by volunteers in rural communities.

INTRODUCTION: The Community Trial of Mammography Promotion assessed the effectiveness of mammography promotion by community volunteer groups in rural areas. Three interventions were tested. One used an individual counseling strategy, one used a community activities strategy, and a third combined the two strategies. METHODS: The effects of the interventions were tested by randomizing 40 communities either to the study interventions or to a control group. A cohort of 352 women from each community was randomly selected and used to evaluate the interventions' effectiveness. Of these, 6592 women were eligible for screening mammography at baseline and follow-up and were successfully interviewed prior to and after study intervention activities. RESULTS: Although the interventions did not significantly increase women's overall use of mammography, the community activities intervention increased use at follow-up by regular users over baseline by 2.9% (p = 0.01). Intervention appears to have increased the use of mammography among certain groups of women who were not regular users at baseline, including those in communities without female physicians (10% to 16%; p < 0.05), and among women with no health insurance (10% to 23%; p </= 0.05). CONCLUSION: Volunteers can effectively promote mammography in rural communities.

Adult↗

Activation of cytochrome P450 gene expression in the rat brain by phenobarbital-like inducers.

Oxidative biotransformation, coupled with genetic variability in enzyme expression, has been the focus of hypotheses interrelating environmental and genetic factors in the etiology of central nervous system disease processes. Chemical modulation of cerebral cytochrome P450 (P450) monooxygenase expression character may be an important determinant of in situ metabolism, neuroendocrine homeostasis, and/or central nervous system toxicity resulting from exposure to neuroactive drugs and xenobiotic substances. To examine the capacity of the rat brain to undergo phenobarbital (PB)-mediated induction, we developed reverse transcription-polymerase chain reaction methods and evaluated the effects of several PB-like inducers on P450 and microsomal epoxide hydrolase gene expression. Animals treated i.p. with four daily doses of PB demonstrated markedly induced levels of CYP2B1, CYP2B2, and CYP3A1 mRNA in the striatum and cerebellum. In contrast, 1 or 2 days of PB treatment resulted in unchanged or even slightly decreased levels of CYP2B1 and CYP2B2 in the brain, although the latter treatments produced marked induction of the corresponding genes in the liver. Only slight increases in epoxide hydrolase RNA levels resulted in brains of PB-treated animals. Substantial activation of cerebral CYP2B1, CYP2B2, and CYP3A1 mRNA levels also resulted when animals were treated with the neuroactive drugs diphenylhydantoin and amitryptiline, and with the potential PB-like xenobiotic inducers trans-stilbene oxide and diallyl sulfide, whereas dichlorodiphenyltrichloroethane was less efficacious. Although the time course of the induction response is delayed in brain relative to that required for the liver, these results clearly establish that brain P450s are markedly PB inducible.

Allyl Compounds↗

The direct antiatherogenic effect of estrogen is present, absent, or reversed, depending on the state of the arterial endothelium. A time course study in cholesterol-clamped rabbits.

BACKGROUND: This study further investigated the relationship between estrogen, arterial endothelium, and nitric oxide (NO) in cholesterol-clamped rabbits. METHODS AND RESULTS: Rabbits were ovariectomized, balloon-injured in the thoracic aorta, and grouped to receive cholesterol-enriched chow together with either 17beta-estradiol or vehicle for 1, 2, 4, or 8 weeks. In the undamaged aorta, cholesterol accumulation of the placebo rabbits was significantly increased from week 4 to 8 (P<0.001). This increase was almost completely inhibited by estrogen (P<0.001). In the balloon-injured aorta, the estrogen and placebo rabbits accumulated similar amounts of cholesterol in the reendothelialized areas. In the deendothelialized areas, the estrogen group surprisingly accumulated significantly more cholesterol than the placebo group. This difference was apparent from week 2 and became significant at week 8 (P<0.01). Circulating nitrite/nitrate were significantly increased by estrogen at weeks 1, 2, and 4 but not at week 8. Similarly, in additional experiments, basal NO release was significantly higher in estrogen-treated than in placebo-treated rabbits after 4 (P<0.05) but not after 8 weeks. Stimulated NO release and endothelial NO synthase activity did not differ between groups. Mononuclear-endothelial cell binding was reduced by 50% by estrogen after 4 weeks (P<0.05). This difference, however, was abolished by coadministration of N(G)-nitro-L-arginine methyl ester, an inhibitor of NO production. CONCLUSIONS: The direct antiatherogenic effect of estrogen was present, absent, or reversed, depending on the state of the arterial endothelium, and preceded by a transient increase in NO production followed by a reduced mononuclear-endothelial cell binding.

Analysis of Variance↗

Involvement in decision-making and breast cancer survivor quality of life.

Advances in treatment for breast cancer have improved women's chances of surviving this disease, while giving patients more treatment options than in the past. This study examined the influence of patient involvement in decision-making on survivor quality of life. A prevalence sample of breast cancer survivors were interviewed about their involvement in decision-making about their cancer treatment and follow-up care. A series of multivariate regression analyses were then conducted to examine how involvement in decision-making about cancer treatment and follow-up care contributed to survivor quality of life. Analyses revealed involvement in decision-making about the use of testing for recurrent disease (TFR) as part of follow-up care is associated with improved quality of life in several domains (p < 0.05). This association of improved quality of life with involvement in decision-making about follow-up TFR was independent of associations of quality of life with surgical treatment received, involvement in decision-making about surgical treatment, frequency of TFR, use of mammography, age, income, education, and years since diagnosis. This suggests that efforts to increase patient involvement in decision-making about follow-up care may improve quality of life for breast cancer survivors.

Aged↗

Prostate-specific antigen for prostate cancer screening. Do physician characteristics affect its use?

PURPOSE: Screening for prostate cancer with the prostate-specific antigen (PSA) test remains controversial. This controversy is reflected in a lack of consensus in the medical literature and among professional and policy organizations regarding routine screening by PSA. It is not known how physicians respond when recommendations from experts are inconsistent. METHODS: A questionnaire was mailed to 1369 primary care physicians in active practice in Washington State in 1994. Response rate to the survey was 63%. Chi-square tests and multivariate logistic regression analysis were used to examine the effects of physician characteristics on physicians' self report of use of the PSA test for screening asymptomatic male patients, aged 50 to 80, for prostate cancer. RESULTS: Of the 714 physicians included in the analysis, 68% reported routine use of PSA. Use of PSA varied among physicians on the basis of practice setting, years since medical school graduation, and whether compensation was fee-for-service or salaried. Male physicians trained before 1974 and physicians receiving fee-for-service were significantly more likely than other physicians to recommend screening by PSA. CONCLUSIONS: Results suggest that physicians' personal characteristics such as year of medical school graduation, gender, and mode of reimbursement are related to self-reported PSA use.

Chi-Square Distribution↗

Prevalence of pedigrees suggestive of hereditary nonpolyposis colorectal cancer among a community sample of women eligible for screening mammography.

OBJECTIVE: To determine from a large cohort of women eligible for screening mammography, the number who would meet criteria for genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC). METHODS: Detailed personal and family cancer histories, obtained from 6,682 women aged 50-80 years randomly selected from communities in Washington State, were matched to the Amsterdam criteria, Bethesda guidelines, and Japanese criteria for HNPCC. RESULTS: One (0.015%) respondent met the Amsterdam criteria, 2 (0.035%) met the Japanese criteria and 5 (0.075%) met the Bethesda guidelines. CONCLUSION: Using the time of presentation for initial mammography as an opportunity to screen for HNPCC would detect very few families at high risk for this condition.

Journal Article↗

Community attitudes and mammography use: does it really matter what other people think?

This study examined whether community characteristics, particularly community attitudes regarding mammography use, are associated with women's use of mammography in rural communities. Forty communities in predominantly rural areas of Washington State were selected for inclusion in this study based on their size and distance from an urban center. Characteristics of the communities were assessed as were characteristics of women living in the communities. From each community, random samples of 352 women between 50 and 80 years old participated by completing a telephone survey that included questions on a variety of topics, including their use of mammography. Logistic regression analyses revealed community of residence to be a significant predictor of individual women's mammography use after adjusting for individual level predictors of mammography use including age, education, employment, marital status, financial situation, and ease of access to medical services. An examination of the influence of community characteristics revealed women living in communities with supportive community attitudes towards mammography use report higher levels of mammography use than do women living in communities with less supportive attitudes. The presence or absence of male or female physicians or of mammography facilities in a local community was not associated with statistically significant effects on women's mammography use. Community attitudes are associated with mammography use in rural communities. Public health interventions that change community attitudes may have effects that extend beyond the people directly contacted by these interventions.

Aged↗

Quantification of multiple human cytochrome P450 mRNA molecules using competitive reverse transcriptase-PCR.

We developed a quantitative competitive reverse transcriptase-polymerase chain reaction (QC RT-PCR) assay to measure mRNA levels of seven human cytochrome P450 (P450, CYP) genes and microsomal epoxide hydrolase (EH) simultaneously. This assay employs an exogenous recombinant RNA (rcRNA) molecule as an internal standard that shares PCR primer and hybridization probe sequences with CYP1A1, CYP1A2, CYP2A6/7, CYP2D6, CYP2E1, CYP2F1, CYP3A4/5/7, and EH mRNA. Because each rcRNA molecule contains several primer sequences, an entire battery of genes that exhibit differential responsiveness to various classes of xenobiotics may be measured simultaneously from one population of cDNA molecules. In this study, we demonstrated the precision and power of the assay using small amounts of human liver total RNA. We also report for the first time quantitative profiles of P450 and EH mRNA abundance in eight human livers. Cytochrome P450 2E1 mRNA maintained the highest abundance (average 6.67 x 10(7) molecules/microg of total RNA) and least variation (13 fold) in all livers examined. Cytochrome P450 1A2, CYP2A6/7, CYP2D6, CYP3A4/5, and EH mRNAs were approximately one order of magnitude less abundant than CYP2E1 transcripts, with CYP2D6 levels exhibiting the greatest variation (220 fold) between individuals. This QC RT-PCR assay should prove valuable for measuring basal and induced mRNAs in different cell types in vitro, as well as in biomonitoring applications where individuals are exposed or hypersusceptible to certain xenobiotic-initiated toxicities.

Adolescent↗

The use of mammography by survivors of breast cancer.

OBJECTIVES: Survivors of breast cancer are at high risk for development of a second breast cancer and are thus a group for whom annual mammography screening is recommended. However, survivors' use of mammography rarely has been examined. METHODS: We surveyed a representative population sample of survivors who lived in rural communities about their mammography use after cancer. RESULTS: Of these women, 30% had not received a mammogram in the preceding year. Predictors of mammography use included physician recommendation and whether the original cancer had been detected by mammography. CONCLUSIONS: Physicians should recommend mammography to survivors of breast cancer to ensure regular use.

Aged↗

Confirmatory analysis of opinions regarding the pros and cons of mammography.

This investigation extends prior research to apply decision-making constructs from the transtheoretical model (TTM) of behavior change to mammography screening. Study subjects were 8,914 women ages 50-80, recruited from 40 primarily rural communities in Washington State. Structural equation modeling showed that favorable and unfavorable opinions about mammography (i.e., pros and cons) fit the observed data. Analysis of variance supported the associations between readiness to obtain screening (i.e., stage of adoption) and opinions about mammography (i.e., decisional balance) previously found in research using smaller samples from another geographic region. This report extends these earlier studies by using structural equation modeling, opinion scales based both on principal component analyses and on a priori definitions, a developmental sample and a confirmatory sample, and by sampling from a different geographic region. It is recommended that future research examine whether opinions regarding the cons of mammography are more individually specific than the pros.

Aged↗