Saturated fat intake and prostate cancer aggressiveness: results from the population-based North Carolina-Louisiana Prostate Cancer Project.

BACKGROUND: Epidemiologic and laboratory evidence supports a role for cholesterol in prostate cancer (PC). Dietary saturated fat content impacts serum cholesterol levels. However, epidemiologic associations between saturated fat and PC aggressiveness are inconsistent. We hypothesized that high saturated fat intake would be associated with increased PC aggressiveness, and that statin use would modify this association. METHODS: Of 1854 PC cases in the North Carolina-Louisiana PC Project, 321 (17%) were classified as high aggressive (Gleason sum ⩾8, PSA>20 ng ml-1, or Gleason sum ⩾7 and clinical stage T3-4) or low/intermediate aggressive (all other cases). Using low/intermediate aggressive cases as the referent group, we examined the association between tertiles of total fat-adjusted saturated fat intake and high aggressive PC using logistic regression, overall and stratified by race and statin use. We examined total fat-adjusted polyunsaturated and monounsaturated fatty acids (PUFA and MUFA, respectively), trans fat and cholesterol intake in secondary analysis. RESULTS: High total fat-adjusted saturated fat intake was associated with an elevated odds ratio (OR) for aggressive PC (ORT3vsT1 1.51; 95% CI 1.10-2.06; P-trend=0.009), with an attenuated association in statin users (ORT3vsT1 1.16; 95% CI 0.67-2.01; P-trend=0.661) compared with non-users (ORT3vsT1 1.71; 95% CI 1.16-2.51; P-trend=0.053). High total fat-adjusted cholesterol intake was associated with aggressive PC in European Americans (ORT3vsT1 1.62; 95% CI 1.02-2.58; P-trend=0.056), but not African Americans (ORT3vsT1 0.92; 95% CI 0.60-1.42; P-trend=0.750). High total fat-adjusted PUFA was inversely associated with PC aggressiveness (ORT3vsT1 0.75; 95% CI 0.55-1.03), although this was not significant. No associations were found between total fat-adjusted MUFA or trans fat and PC aggressiveness. CONCLUSIONS: High total fat-adjusted saturated fat intake was associated with increased PC aggressiveness, with a suggestion of a stronger effect in men not using statins. The association between total fat-adjusted cholesterol intake and PC aggressiveness was most pronounced in European Americans.

Preoperative quality of life and surgical outcomes in gynecologic oncology patients: a new predictor of operative risk?

OBJECTIVE: Quality of life (QoL) for women with gynecologic malignancies is predictive of chemotherapy related toxicity and overall survival but has not been studied in relation to surgical outcomes and hospital readmissions. Our goal was to evaluate the association between baseline, pre-operative QoL measures and 30-day post-operative morbidity and health resource utilization by gynecologic oncology patients. METHODS: We analyzed prospectively collected survey data from an institution-wide cohort study. Patients were enrolled from 8/2012 to 6/2013 and medical record data was abstracted (demographics, comorbid conditions, and operative outcomes). Responses from several validated health-related QoL instruments were collected. Bivariate tests and multivariable linear and logistic regression models were used to evaluate factors associated with QoL scores. RESULTS: Of 182 women with suspected gynecologic malignancies, 152 (84%) were surveyed pre-operatively and 148 (81%) underwent surgery. Uterine (94; 63.5%), ovarian (26; 17.5%), cervical (15; 10%), vulvar/vaginal (8; 5.4%), and other (5; 3.4%) cancers were represented. There were 37 (25%) cases of postoperative morbidity (PM), 18 (12%) unplanned ER visits, 9(6%) unplanned clinic visits, and 17 (11.5%) hospital readmissions (HR) within 30days of surgery. On adjusted analysis, lower functional well-being scores resulted in increased odds of PM (OR 1.07, 95%CI 1.01-.1.21) and HR (OR 1.11, 95%CI 1.03-1.19). A subjective global assessment score was also strongly associated with HR (OR 1.89, 95%CI 1.14, 3.16). CONCLUSION: Lower pre-operative QoL scores are significantly associated with post-operative morbidity and hospital readmission in gynecologic cancer patients. This relationship may be a novel indicator of operative risk.

Identification of a novel human cytokine gene in the interleukin gene cluster on chromosome 2q12-14.

Genes in the interleukin-1 (IL-1) gene cluster on human chromosome 2 play an important role in mediating inflammatory responses and are associated with numerous diseases. We have identified a novel IL-1-like gene, IL-1F10, on human chromosome 2q13-14.1 near the IL-1 receptor antagonist gene (IL-1RN). The IL1F10 gene is encoded by 5 exons spanning over 7.8 kb of genomic DNA. The 1008-bp IL-1F10 cDNA encodes a 152-amino acid protein that shares between 41% and 43% amino acid identity with human IL-1 receptor antagonist (IL-1Ra) and FIL-1delta, respectively. IL-1F10 shares characteristics of the IL-1Ra family, including key amino acid consensus sequences and a similar genomic structure. By multitissue first-strand cDNA PCR analysis, IL-1F10 mRNA is expressed in heart, placenta, fetal liver, spleen, thymus, and tonsil. The expression in a variety of immune tissues and similarity to IL-1Ra suggest a role of IL-1F10 in the inflammatory response.

A high-resolution 6.0-megabase transcript map of the type 2 diabetes susceptibility region on human chromosome 20.

Recent linkage studies and association analyses indicate the presence of at least one type 2 diabetes susceptibility gene in human chromosome region 20q12-q13.1. We have constructed a high-resolution 6.0-megabase (Mb) transcript map of this interval using two parallel, complementary strategies to construct the map. We assembled a series of bacterial artificial chromosome (BAC) contigs from 56 overlapping BAC clones, using STS/marker screening of 42 genes, 43 ESTs, 38 STSs, 22 polymorphic, and 3 BAC end sequence markers. We performed map assembly with GraphMap, a software program that uses a greedy path searching algorithm, supplemented with local heuristics. We anchored the resulting BAC contigs and oriented them within a yeast artificial chromosome (YAC) scaffold by observing the retention patterns of shared markers in a panel of 21 YAC clones. Concurrently, we assembled a sequence-based map from genomic sequence data released by the Human Genome Project, using a seed-and-walk approach. The map currently provides near-continuous coverage between SGC32867 and WI-17676 ( approximately 6.0 Mb). EST database searches and genomic sequence alignments of ESTs, mRNAs, and UniGene clusters enabled the annotation of the sequence interval with experimentally confirmed and putative transcripts. We have begun to systematically evaluate candidate genes and novel ESTs within the transcript map framework. So far, however, we have found no statistically significant evidence of functional allelic variants associated with type 2 diabetes. The combination of the BAC transcript map, YAC-to-BAC scaffold, and reference Human Genome Project sequence provides a powerful integrated resource for future genomic analysis of this region.

Usefulness of cardiovascular family history data for population-based preventive medicine and medical research (the Health Family Tree Study and the NHLBI Family Heart Study).

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family Tree Study, and 1,442 families in the NHLBI Family Heart Study in Massachusetts, Minnesota, North Carolina, and Utah. Utah families with a positive family history of CHD (FRS > or =0.5) represented only 14% of the general population but accounted for 72% of persons with early CHD (men before age 55 years, women before age 65 years) and 48% of CHD at all ages. For strokes, 11% of families with FRS > or =0.5 accounted for 86% of early strokes (<75 years) and 68% of all strokes. Analyses of >5,000 families sampled each year in Utah for 14 years demonstrated a gradual decrease in the frequency of a strong positive family history of CHD (-26%/decade) and stroke (-15%/decade) that paralleled a decrease in incidence rates (r = 0.86, p <0.001 for CHD; r = 0.66, p <0.01 for stroke). Because of the collaboration of schools, health departments, and medical schools, the Health Family Tree Study proved to be a highly cost-efficient method for identifying 17,064 CHD-prone families and 13,106 stroke-prone families (at a cost of about $27 per high-risk family) in whom well-established preventive measures can be encouraged. We conclude that most early cardiovascular events in a population occur in families with a positive family history of cardiovascular disease. Family history collection is a validated and relatively inexpensive tool for family-based preventive medicine and medical research.

Family risk score of coronary heart disease (CHD) as a predictor of CHD: the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI family heart study.

Family history of coronary heart disease (CHD) has been found to be a risk factor for CHD in numerous studies. Few studies have addressed whether a quantitative measure of family history of CHD (family risk score, FRS) predicts CHD in African Americans. This study assessed the association between FRS and incident CHD of participants, and the variation of the association by gender and race. Participants in the study were a biracial population-based cohort with 3,958 African Americans and 10,580 Whites aged 45-64 years old in the ARIC baseline survey (1987-1989). They were randomly selected from four U. S. communities. During follow-up (1987-1993), 352 participants experienced the onset of CHD. Incidence density of CHD (per 1,000 person-years) was 7.8 and 3.6 among African-American men (AAM) and women (AAW), and 7.2 and 2.2 among White men (WM) and women (WW). The hazard rate ratio (HRR) of CHD associated with one standard deviation increase of FRS was 1.52 in AAW, 1.46 in AAM, 1.41 in WW, and 1.68 in WM. The HRRs decreased 4.6% in AAW, 1.4% in WW, 5.7% in AAM, and 3.0% in WM, but increased 2.1% in AAM after adjustment for selected covariates. FRS predicts incident CHD in African Americans and Whites, men and women. The relation of FRS to incident CHD can be only partially explained by the selected risk factors in the biological causal pathways: IMT, T-G, LDL, HDL, Lp(a), fibrinogen and hypertension. No significant difference by race has been found in this study.

Accuracy of proband reported family history: the NHLBI Family Heart Study (FHS).

Proband-reported family histories are widely used in research and counseling, yet little is known about the validity of family history reporting. The Family Heart Study (FHS), a population-based study of familial cardiovascular disease, gathered family history information from 3,020 middle-aged probands in four U.S. communities. Probands reported on the history of coronary heart disease (CHD), diabetes, hypertension, and asthma among a total of 10,316 living relatives (9,186 siblings, 1,130 parents) and 2,685 spouses. Questionnaires were returned by 6,672 siblings, 901 parents, and 2,347 spouses, yielding response rates of 73, 79, and 87%, respectively. Utilizing the relatives' self-report as the standard, sensitivity of the proband report on their spouse, parent, and sibling was 87, 85, and 81% for CHD, 83, 87, and 72% for diabetes, 77, 76, and 56% for hypertension, and 66, 53, and 39% for asthma, respectively. Most specificity values were above 90%. Analyses using generalized estimating equations (GEE) were performed to evaluate differences in proband accuracy based on the proband's age, gender, disease state, center, and ethnicity. In multivariate models, age, gender, and disease status were significantly associated with the accuracy of proband's report of sibling disease history, but had little effect on the accuracy of their report on spouses or parents. In general, older probands were significantly less accurate reporters of disease than younger probands. These results demonstrate that CHD family history can be captured effectively based on proband reports, but suggest that additional family contacts may be helpful when working with older probands or with chronic diseases that have few recognized medical events or procedures.

Family history of coronary heart disease and pre-clinical carotid artery atherosclerosis in African-Americans and whites: the ARIC study: Atherosclerosis Risk in Communities.

The association between family history of coronary heart disease (CHD) and morbidity and mortality due to atherosclerotic sequelae, although well documented in population-based samples of whites, has been little studied in African Americans. Less is known about the relationship between a family history of CHD and pre-clinical atherosclerosis. We report the relation between family history of CHD, summarized in a family risk score (FRS), and asymptomatic atherosclerosis at the extracranial carotid arteries, measured by B-mode ultrasound. The FRS was assessed in relatives of 3,034 African Americans and 9,048 white probands aged 45 to 64 years, in the four community-based cohorts of the ARIC Study. The analyses were restricted to individuals free of clinically manifest CHD. The distribution of CHD FRS by ethnic-gender groups was right skewed, with slightly higher mean values for white than African-American males, and for African-American than white females. In a series of multivariate linear regression models with mean carotid artery intima-media wall thickness (IMT) as the dependent variable, FRS was associated positively with IMT in white and African-American women and white men. In a multiple regression model, approximately one-half of the quantitative statistical relationship of the CHD FRS with IMT in whites was statistically explained by the major risk factors considered as intervening, explanatory variables in this analysis. This association in African-American women was fully explained by the major risk factors. The FRS was not, however, associated with atherosclerosis or major risk factors in African-American males, in the ARIC Study.

First report of management and outcome of pregnancies associated with hereditary orotic aciduria.

Two pregnancies in a 25-year-old woman with hereditary orotic aciduria who was managed prenatally on uridine therapy are described. The first pregnancy resulted in an infant with multiple congenital anomalies and a 47,xx,inv(4)(p12q25), +der(22)t(11;22)(p23;q11) karyotype. The proposita was found to be a carrier of a de novo 11;22 translocation and a pericentric inversion of chromosome 4. Subsequently, several carriers of orotic aciduria in this family were identified with the inverted chromosome 4. The second pregnancy resulted in a normal male with an inverted chromosome 4.

Open spina bifida: does cesarean section delivery improve prognosis?

Records were reviewed retrospectively on 72 infants with open spina bifida followed from birth through one year of age. Thirty-two infants were born by cesarean section and 40 vaginally. The following variables were compared between the two groups: 1) mortality in the nursery and between nursery discharge and one year of age, 2) incidence of meningitis in the neonatal period, 3) length of initial hospital stay, and 4) neurologic and developmental status at one year. No significant differences were noted between the two groups. Although it has been suggested that cesarean section may improve the prognosis for infants with open spina bifida, our data do not support that conclusion.

A mildly retarded woman with 46,XX/47,XX, + 18 mosaicism.

We describe a mildly retarded woman with trisomy 18 mosaicism. The phenotype did not suggest trisomy 18, but the mild mental retardation, asymmetric face with bushy eyebrows and thick lips, short stature, and older maternal age raised the suspicion of a chromosomal cause for her condition.