Pre-eclampsia screening in Denmark (PRESIDE): national validation study.

OBJECTIVES: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for pre-eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. METHODS: This was a prospective study of women with a singleton pregnancy attending for their first-trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre-eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre-eclampsia diagnosis, was recorded. Pre-eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen-positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. RESULTS: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1-33.9) years. The majority were white (95%), naturally conceiving (90%), non-smokers (97%) and had no family history of pre-eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2-26.6) kg/m2 . A complete risk assessment including maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A was available for 8156 women (92.9%). In these women, UtA-PI was measured bilaterally with a median value of 1.58 (IQR, 1.27-1.94) and the median resting MAP of 80.5 (IQR, 76.1-85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre-eclampsia, including 55 (0.7%) cases of pre-eclampsia with delivery < 37 weeks of gestation and 16 (0.2%) cases of pre-eclampsia with delivery < 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A had a DR of 77.4% (95% CI, 57.6-97.2%) for pre-eclampsia with delivery < 34 weeks, 66.8% (95% CI, 54.4-79.1%) for pre-eclampsia with delivery < 37 weeks and 44.1% (95% CI, 38.5-49.7%) for pre-eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre-eclampsia with delivery < 34 weeks and 19.6% of women with pre-eclampsia with delivery < 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA-PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9-84.1%) for PE with delivery < 34 weeks and 45.2% (95% CI, 32.0-58.5%) for PE with delivery < 37 weeks. CONCLUSION: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A predicted 77.4% of cases with pre-eclampsia with delivery < 34 weeks and 66.8% of cases with pre-eclampsia with delivery < 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Recurrence of Breast Cancer After Primary Treatment: A Matched Comparison Study of Disease-Free Survival in Women Who Do and Do Not Receive Adjunctive Naturopathic Oncology Care.

PURPOSE: To compare disease free survival experienced by women who received usual oncologic care compared to a cohort of women who received naturopathic oncology care in addition to usual care. METHODS: Women with breast cancer who received naturopathic oncology (NO) care in Western Washington State (WA) (N = 176) were recruited to a prospective study of clinical health-related quality of life outcomes and then matched to women who received usual care (UC) only (N = 334). RESULTS: Among 510 women with breast cancer stages 1 to 3, a total of 50 women (10%) experienced a disease-free survival (DFS) ending event within the observation period; 23 (6.8% of those in the UC cohort, and 27 (15.3% of those in the NO cohort (P < .05). Although, women in the 2 cohorts received similar surgical, chemotherapy, and radiation treatment, women with breast cancer who received naturopathic oncology adjunctive care were less likely to use anti-estrogen therapy, and experienced poorer DFS (logrank test, P < .05). However, differences in DFS could not be shown to be due to cohort differences in anti-estrogen therapy, baseline HRQOL, or naturopathic oncology therapies prescribed. The stage 3 women in the naturopathic oncology group had more advanced disease at diagnosis. They were more likely to have 5 or more metastatic lymph nodes at baseline (18.5%) compared to their usual care matched control group (13%). Women in the naturopathic oncology group also had higher grade tumors at diagnosis. CONCLUSIONS: Results show that recurrence of breast cancer was associated with more advanced malignant lymph node involvement; and that naturopathic oncology services provided in 2009-2015 did not improve disease-free survival in these high-risk breast cancer patients.

The gold-standard genome of Aspergillus niger NRRL 3 enables a detailed view of the diversity of sugar catabolism in fungi.

The fungal kingdom is too large to be discovered exclusively by classical genetics. The access to omics data opens a new opportunity to study the diversity within the fungal kingdom and how adaptation to new environments shapes fungal metabolism. Genomes are the foundation of modern science but their quality is crucial when analysing omics data. In this study, we demonstrate how one gold-standard genome can improve functional prediction across closely related species to be able to identify key enzymes, reactions and pathways with the focus on primary carbon metabolism. Based on this approach we identified alternative genes encoding various steps of the different sugar catabolic pathways, and as such provided leads for functional studies into this topic. We also revealed significant diversity with respect to genome content, although this did not always correlate to the ability of the species to use the corresponding sugar as a carbon source.

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis.

Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (q<0.20). The results suggest that genetic variants related to increased IL-1ß levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-γ levels may be favorable when treating psoriasis with ustekinumab.

Conditioned pain modulation is not decreased after partial sleep restriction.

BACKGROUND: Sleep problems have been identified as a risk factor for several chronic pain conditions. Reduced sleep has been related to increased pain perception and it has been hypothesized that reduced pain inhibition may explain this. The aim of this study was to determine if sleep restriction (SR) affects heat pain perception and conditioned pain modulation (CPM). METHODS: In a paired cross-over design with two conditions (2 nights habitual sleep (HS) vs. 2 nights 50% SR) CPM was tested in 22 healthy individuals (14 women, 8 men). The test stimulus (TS) was 2-min contact heat stimulation (47  ± 1.3  °C) to the volar forearm. TS was delivered before and during a 7 °C cold pressor test (conditioning stimulus, CS) to the contralateral hand. RESULTS: TS was perceived as more painful after SR compared to after HS (p < 0.001). A stronger inhibitory CPM was found after SR versus after HS (p < 0.001). CONCLUSIONS: The results indicate that SR leads to increased heat pain perception, but not reduced inhibitory CPM. This contradicts general assumptions on the relation between SR and the CPM effect.

Circulating ACE is a predictor of weight loss maintenance not only in overweight and obese women, but also in men.

BACKGROUND: Circulating angiotensin-converting enzyme (ACE) was identified as a predictor of weight loss maintenance in overweight/obese women of the Diogenes project. OBJECTIVE: To investigate whether ACE acted also as a predictor in men of the Diogenes study and to compare it with that in women. DESIGN: Subjects, who lost ≥ 8% of body weight induced by low-caloric diet in an 8-week weight loss period, were assigned to weight loss maintenance with dietary intervention for 6 months. SUBJECTS: 125 overweight/obese healthy men from eight European countries who completed whole intervention. MEASUREMENTS: Concentrations and activity of serum ACE at baseline and after the 8-week weight loss, in addition to anthropometric and physiological parameters. RESULTS: Serum ACE concentration decreased by 11.3 ± 10.6% during the weight loss period in men. A greater reduction is associated with less body weight regain during the maintenance period (r=0.227, P=0.012). ACE change was able to predict a weight regain ≤ 20% after 6 months, with an odds ratio of 1.59 (95% confidence interval (CI): 1.09-2.33, P=0.016) for every 10% reduction, which was independent of body mass index and weight loss. The prediction power was weaker in men than in women, but without a significant sex difference (P=0.137). In pooled subjects (N=218), the odds ratio was 1.96 (95% CI: 1.46-2.64, P<0.001). CONCLUSIONS: A greater reduction of ACE during weight loss is favorable for weight maintenance in both men and women. This can offer useful information for personalized advice to improve weight loss maintenance. It also confirms the role of ACE in the metabolic pathways of weight regulation.

Overexpression of isocitrate lyase-glyoxylate bypass influence on metabolism in Aspergillus niger.

In order to improve the production of succinate and malate by the filamentous fungus Aspergillus niger the activity of the glyoxylate bypass pathway was increased by over-expression of the isocitrate lyase (icl) gene. The hypothesis was that when isocitrate lyase was up-regulated the flux towards glyoxylate would increase, leading to excess formation of malate and succinate compared to the wild-type. However,metabolic network analysis showed that an increased icl expression did not result in an increased glyoxylate bypass flux. The analysis did show a global response with respect to gene expression, leading to an increased flux through the oxidative part of the TCA cycle. Instead of an increased production of succinate and malate, a major increase in fumarate production was observed. The effect of malonate, a competitive inhibitor of succinate dehydrogenase (SDH), on the physiological behaviour of the cells was investigated. Inhibition of SDH was expected to lead to succinate production, but this was not observed. There was an increase in citrate and oxalate production in the wild-type strain. Further more, in the strain with over-expression of icl the organic acid production shifted from fumarate towards malate production when malonate was added to the cultivation medium. Overall,the icl over-expression and malonate addition had a significant impact on metabolism and on organic acid production profiles. Although the expected succinate and malate formation was not observed, a distinct and interesting production of fumarate and malate was found.

Current status of systems biology in Aspergilli.

In this review, we present a comprehensive overview of the current status of genomics, transcriptomics, proteomics, metabolomics, and metabolic modeling in Aspergillus species. Currently, 13 Aspergillus genomes divided across seven species have been sequenced with more to come, and many applications of this information on a systems level have been published. More than 30 studies on global transcription analysis have been published, and 21 different platforms are available for Aspergillus transcription studies. Additionally, the fields of proteomics and metabolomics have, while still in their infancy, produced intriguing results and novel applications. Finally, multiple levels of Aspergillus metabolism have been reconstructed and modelled. Systems-level research of Aspergilli have in a few years added to our knowledge on processes relevant to evolution, central and secondary metabolism, cellular organization, pathogenicity and biotechnology and future efforts may lead to much improved understanding of regulation of key cellular processes in this important family of filamentous fungi.

Oleanolic acid induces relaxation and calcium-independent release of endothelium-derived nitric oxide.

BACKGROUND AND PURPOSE: The present study investigated the mechanisms by which oleanolic acid, a component of olive oil, increases release of nitric oxide (NO). EXPERIMENTAL APPROACH: Measurements of isometric tension, NO concentration, or endothelial cell calcium were made in rat isolated mesenteric arteries. Immunoblotting for endothelial NOS (eNOS) and Akt kinase were performed in primary cultures of human umbilical vein endothelial cells (HUVECs). KEY RESULTS: Oleanolic acid (3-30 microM) evoked endothelium-dependent relaxations in noradrenaline-contracted rat superior and small mesenteric arteries. In rat superior mesenteric arteries, oleanolic acid induced simultaneous increases in NO concentration and relaxation, and these responses were inhibited by an inhibitor of NOS, asymmetric dimethyl-L-arginine (300 microM) and by the NO scavenger, oxyhaemoglobin (10 microM). Oleanolic acid-evoked NO increases were not reduced in Ca(2+)-free solution and in the presence of an inhibitor of endoplasmic reticulum calcium-ATPase, thapsigargin (1 microM). Oleanolic acid evoked relaxation without changes in endothelial cell calcium, but decreased smooth muscle calcium in arterial segments. Oleanolic acid failed to increase calcium in HUVECs, but increased time-dependently phosphorylation of Akt kinase at Serine(473) (Akt-Ser(473)) and eNOS at Serine(1177) (eNOS-Ser(1177)), which was attenuated by inhibitors of phosphoinositide-3-kinase. CONCLUSIONS AND IMPLICATIONS: This study provides direct evidence that a component of olive oil, oleanolic acid, activated endothelium-dependent release of NO and decreased smooth muscle cell calcium followed by relaxation. The oleanolic acid-evoked endothelium-derived NO release was independent of endothelial cell calcium and involved phosphoinositide-3-kinase-dependent phosphorylation of Akt-Ser(473) followed by phosphorylation of eNOS-Ser(1177).

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.

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.

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.

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.

Meeting the needs of rural breast cancer survivors: what still needs to be done?

As screening and treatment for breast cancer improve, learning about survivors' post-treatment needs becomes increasingly important. Focus groups (n = 23) were conducted with breast cancer survivors (n = 128) in rural Washington communities during a 5-month period in 1996 to explore ways to improve the lives of rural breast cancer survivors and to expand existing knowledge of breast cancer survivorship. Survivors reported positive and negative outcomes of their cancer experience. Results indicate that the needs of many women with breast cancer, particularly women diagnosed with late-stage disease, are not being met. Participants diagnosed with late-stage cancer were more likely than participants diagnosed with early-stage cancer to comment about being treated poorly by the medical system and to voice a need for increased support and educational services for breast cancer patients. Rural survivors, regardless of stage at diagnosis, reported needing more education about breast cancer and more emotional support after diagnosis. Further efforts to facilitate support and education within the context of medical care and to improve patient-clinician relationships are needed.

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.

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.

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.

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

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.

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.