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Biomedical subjects

J D Potter

Publications and source records attributed to J D Potter.

At least 19 recordsLinked to original sources
PubMed2000

Altered regulation of cardiac muscle contraction by troponin T mutations that cause familial hypertrophic cardiomyopathy.

To study the effect of troponin (Tn) T mutations that cause familial hypertrophic cardiomyopathy (FHC) on cardiac muscle contraction, wild-type, and the following recombinant human cardiac TnT mutants were cloned and expressed: I79N, R92Q, F110I, E163K, R278C, and intron 16(G(1) --> A) (In16). These TnT FHC mutants were reconstituted into skinned cardiac muscle preparations and characterized for their effect on maximal steady state force activation, inhibition, and the Ca(2+) sensitivity of force development. Troponin complexes containing these mutants were tested for their ability to regulate actin-tropomyosin(Tm)-activated myosin-ATPase activity. TnT(R278C) and TnT(F110I) reconstituted preparations demonstrated dramatically increased Ca(2+) sensitivity of force development, while those with TnT(R92Q) and TnT(I79N) showed a moderate increase. The deletion mutant, TnT(In16), significantly decreased both the activation and the inhibition of force, and substantially decreased the activation and the inhibition of actin-Tm-activated myosin-ATPase activity. ATPase activation was also impaired by TnT(F110I), while its inhibition was reduced by TnT(R278C). The TnT(E163K) mutation had the smallest effect on the Ca(2+) sensitivity of force; however, it produced an elevated activation of the ATPase activity in reconstituted thin filaments. These observed changes in the Ca(2+) regulation of force development caused by these mutations would likely cause altered contractility and contribute to the development of FHC.

Amino Acid Sequence↗
PubMed1999

Breast-feeding and risk of childhood acute leukemia.

BACKGROUND: Breast-feeding is well known to have a protective effect against infection in infants. Although the long-term effects of breast-feeding on childhood cancer have not been studied extensively, a protective effect against childhood Hodgkin's disease and lymphoma has been suggested previously from small investigations. In this study, we tested the hypothesis that breast-feeding decreases the risk of childhood acute leukemia. METHODS: A total of 1744 children with acute lymphoblastic leukemia (ALL) and 1879 matched control subjects, aged 1-14 years, and 456 children with acute myeloid leukemia (AML) and 539 matched control subjects, aged 1-17 years, were included in the analysis. Information regarding breast-feeding was obtained through telephone interviews with mothers. All leukemias combined, histologic type of leukemia (ALL versus AML), immunophenotype of ALL (early pre-B cell, pre-B cell, or T cell), and morphology of AML were assessed separately in the data analysis. RESULTS: Ever having breast-fed was found to be associated with a 21% reduction in risk of childhood acute leukemias (odds ratio [OR] for all types combined = 0.79; 95% confidence interval [CI] = 0.70-0.91). A reduction in risk was seen separately for AML (OR = 0.77; 95% CI = 0.57-1.03) and ALL (OR = 0.80; 95% CI = 0.69-0.93). The inverse associations were stronger with longer duration of breast-feeding for total ALL and AML; for M0, M1, and M2 morphologic subtypes of AML; and for early pre-B-cell ALL. CONCLUSION: In this study, breast-feeding was associated with a reduced risk of childhood acute leukemia. If confirmed in additional epidemiologic studies, our findings suggest that future epidemiologic and experimental efforts should be directed at investigating the anti-infective and/or immune-stimulatory or immune-modulating effects of breast-feeding on leukemogenesis in children.

Acute Disease↗
PubMed1999

Metal-ion affinity and specificity in EF-hand proteins: coordination geometry and domain plasticity in parvalbumin.

BACKGROUND: The EF-hand family is a large set of Ca(2+)-binding proteins that contain characteristic helix-loop-helix binding motifs that are highly conserved in sequence. Members of this family include parvalbumin and many prominent regulatory proteins such as calmodulin and troponin C. EF-hand proteins are involved in a variety of physiological processes including cell-cycle regulation, second messenger production, muscle contraction, microtubule organization and vision. RESULTS: We have determined the structures of parvalbumin mutants designed to explore the role of the last coordinating residue of the Ca(2+)-binding loop. An E101D substitution has been made in the parvalbumin EF site. The substitution decreases the Ca(2+)-binding affinity 100-fold and increases the Mg(2+)-binding affinity 10-fold. Both the Ca(2+)- and Mg(2+)-bound structures have been determined, and a structural basis has been proposed for the metal-ion-binding properties. CONCLUSIONS: The E101D mutation does not affect the Mg(2+) coordination geometry of the binding loop, but it does pull the F helix 1.1 A towards the loop. The E101D-Ca(2+) structure reveals that this mutant cannot obtain the sevenfold coordination preferred by Ca(2+), presumably because of strain limits imposed by tertiary structure. Analysis of these results relative to previously reported structural information supports a model wherein the characteristics of the last coordinating residue and the plasticity of the Ca(2+)-binding loop delimit the allowable geometries for the coordinating sphere.

Animals↗
PubMed1999

The role of the NH(2)- and COOH-terminal domains of the inhibitory region of troponin I in the regulation of skeletal muscle contraction.

The role of the inhibitory region of troponin (Tn) I in the regulation of skeletal muscle contraction was studied with three deletion mutants of its inhibitory region: 1) complete (TnI-(Delta96-116)), 2) the COOH-terminal domain (TnI-(Delta105-115)), and 3) the NH(2)-terminal domain (TnI-(Delta95-106)). Measurements of Ca(2+)-regulated force and relaxation were performed in skinned skeletal muscle fibers whose endogenous TnI (along with TnT and TnC) was displaced with high concentrations of added troponin T. Reconstitution of the Tn-displaced fibers with a TnI.TnC complex restored the Ca(2+) sensitivity of force; however, the levels of relaxation and force development varied. Relaxation of the fibers (pCa 8) was drastically impaired with two of the inhibitory region deletion mutants, TnI-(Delta96-116).TnC and TnI-(Delta105-115).TnC. The TnI-(Delta95-106).TnC mutant retained approximately 55% relaxation when reconstituted in the Tn-displaced fibers. Activation in skinned skeletal muscle fibers was enhanced with all TnI mutants compared with wild-type TnI. Interestingly, all three mutants of TnI increased the Ca(2+) sensitivity of contraction. None of the TnI deletion mutants, when reconstituted into Tn, could inhibit actin-tropomyosin-activated myosin ATPase in the absence of Ca(2+), and two of them (TnI-(Delta96-116) and TnI-(Delta105-115)) gave significant activation in the absence of Ca(2+). These results suggest that the COOH terminus of the inhibitory region of TnI (residues 105-115) is much more critical for the biological activity of TnI than the NH(2)-terminal region, consisting of residues 95-106. Presumably, the COOH-terminal domain of the inhibitory region of TnI is a part of the Ca(2+)-sensitive molecular switch during muscle contraction.

Amino Acid Sequence↗
PubMed1999

Optical spectroscopic characterization of single tryptophan mutants of chicken skeletal troponin C: evidence for interdomain interaction.

The effects of metal ion binding on the optical spectroscopic properties and temperature stability of two single tryptophan mutants of chicken skeletal TnC, F78W and F154W, have been examined. The absence of tyrosine and other tryptophan residues allowed the unambiguous assignment of the spectral signal from the introduced Trp residue. Changes in the molar ellipticity values in the far-UV CD spectra of the mutant proteins on metal ion binding were similar to those of wild-type TnC suggesting that the introduction of the Trp residue had no effect on the total secondary structure content. The fluorescence and near-UV absorbance data reveal that, in the apo state, Trp-78 is buried while Trp-154 is exposed to solvent. Additionally, the highly resolved (1)L(b) band of Trp-78 seen in the near-UV absorbance and CD spectra of the apo state of F78W suggest that this residue is likely in a rigid molecular environment. In the calcium-saturated state, Trp-154 becomes buried while the solvent accessibility of Trp-78 increases. The fluorescence emission and near-UV CD of Trp-78 in the N-terminal domain were sensitive to calcium binding at the C-terminal domain sites. Measurements of the temperature stability reveal that events occurring in the N-terminal domain affect the stability of the C-terminal domain and vice versa. This, coupled with the titration data, strongly suggests that there are interactions between the N- and C-terminal domains of TnC.

Acrylamide↗
PubMed1999

Rotational and translational motion of troponin C.

Time resolved fluorescence anisotropy and sedimentation velocity has been used to study the rotational and translational hydrodynamic behavior of two mutants of chicken skeletal troponin C bearing a single tryptophan residue at position 78 or 154 in the metal-free-, metal-bound-, and troponin I peptide (residues 96-116 of troponin I)-ligated states. The fluorescence anisotropy data of both mutants were adequately described by two rotational correlation times, and these are compared with the theoretically expected values based on the rotational diffusion of an idealized dumbbell. These data imply that the motion of the N- and C-terminal domains of troponin C are independent. They also suggest that in the metal-free, calcium-saturated and calcium-saturated troponin I peptide-bound states, troponin C is elongated, having an axial ratio of 4-5. Calcium or magnesium binding to the high affinity sites alone reduces the axial ratio to approximately 3. However, with calcium bound to sites III and IV and in the presence of a 1:1 molar ratio of the troponin I peptide, troponin C is approximately spherical. The metal ion and troponin I peptide-induced length changes in troponin C may play a role in the mechanism by which the regulatory function of troponin C is effected.

Animals↗
PubMed1999

Colorectal cancer: molecules and populations.

The epidemiology and molecular biology of colorectal cancer are reviewed with a view to understanding their interrelationship. Risk factors for colorectal neoplasia include a positive family history, meat consumption, smoking, and alcohol consumption. Important inverse associations exist with vegetables, nonsteroidal anti-inflammatory drugs (NSAIDs), hormone replacement therapy, and physical activity. There are several molecular pathways to colorectal cancer, especially the APC (adenomatous polyposis coli)-beta-catenin-Tcf (T-cell factor; a transcriptional activator) pathway and the pathway involving abnormalities of DNA mismatch repair. These are important, both in inherited syndromes (familial adenomatous polyposis [FAP] and hereditary nonpolyposis colorectal cancer [HNPCC], respectively) and in sporadic cancers. Other less well defined pathways exist. Expression of key genes in any of these pathways may be lost by inherited or acquired mutation or by hypermethylation. The roles of several of the environmental exposures in the molecular pathways either are established (e.g., inhibition of cyclooxygenase-2 by NSAIDs) or are suggested (e.g., meat and tobacco smoke as sources of specific blood-borne carcinogens; vegetables as a source of folate, antioxidants, and inducers of detoxifying enzymes). The roles of other factors (e.g., physical activity) remain obscure even when the epidemiology is quite consistent. There is also evidence that some metabolic pathways, e.g., those involving folate and heterocyclic amines, may be modified by polymorphisms in relevant genes, e.g., MTHFR (methylenetetrahydrofolate reductase) and NAT1 (N-acetyltransferase 1) and NAT2. There is at least some evidence that the general host metabolic state can provide a milieu that enhances or reduces the likelihood of cancer progression. Understanding the roles of environmental exposures and host susceptibilities in molecular pathways has implications for screening, treatment, surveillance, and prevention.

Adenomatous Polyposis Coli↗
PubMed1999

Intake of fluids and methylxanthine-containing beverages: association with colon cancer.

Although diet and its constituents have been studied extensively as risk factors for colon cancer, much less is known about how specific types of fluid influence colon cancer risk. In this study, we explored associations between colon cancer and total fluids, water and methylxanthine-containing beverages such as coffee, tea and cola; data were obtained from 1,993 incident cases of colon cancer and 2,410 population-based controls living in California, Utah and Minnesota. Our primary objective was to determine the influence on associations of amount consumed, confounding and effect modification. We observed few important differences between colon cancer and fluid consumption for all subjects combined. Among men, low levels of coffee intake were associated with an increased risk of colon cancer relative to non-consumers of coffee (OR 1.32, 95% CI 1.02-1.67), while at high levels of consumption, an inverse association was observed (OR 0.81, 95% CI 0.58-1.12). The observed associations were only slightly influenced by consumption of water or other potential confounding factors, but changing the referent group to those consuming one cup of coffee per day or less resulted in a stronger association and a more significant inverse linear trend (OR 0.71, 95% CI 0.53-0.96). The associations with coffee and caffeine- and methylxanthine-containing beverages were strongest for proximal tumors in men. High levels of water intake, however, were protective for distal tumors (OR for men 0.68, 95% CI 0.49-0.96). Assessment of the impact of smoking on associations between colon cancer and coffee showed a significant interaction between smoking and coffee for both men and women.

Adult↗
PubMed1999

Parental cigarette smoking and the risk of acute leukemia in children.

BACKGROUND: Studies of the relation between parental smoking and childhood leukemia have produced inconsistent results. In the largest case-control studies of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) conducted to date, the authors evaluated leukemia risk relative to parental self-report of cigarette smoking. METHODS: In telephone interviews in which a structured questionnaire was used, parents of 1842 ALL patients, 517 AML patients, and their matched controls were asked about their cigarette smoking habits before, during, and after the pregnancy with the index child. Risk of leukemia was examined by histologic type, age of the child at diagnosis, immunophenotype (for ALL), and French-American-British morphology group (for AML). RESULTS: The risk of ALL was not associated with the father's ever having smoked (odds ratio [OR] = 1.04, 95% confidence interval [CI] 0.90-1.20) or the mother's ever having smoked (OR = 1.04, 95% CI 0.91-1.19). Similarly, no significant risk of AML was observed for paternal (OR = 0.88, 95% CI 0.67-1.16) or maternal smoking (OR = 0.95, 95% CI 0.74-1.22). The relative risk of leukemia was not significantly different from the null for parental smoking in any time period during or around the index pregnancy, nor was it related to the number of cigarettes, the number of years of smoking, or the number of pack-years. A small number of sporadic, statistically significant associations were found, but overall there appeared to be no association between parental cigarette smoking and ALL or AML, or any subgroup of leukemia. CONCLUSIONS: Parental smoking while pregnant or exposure to cigarette smoke shortly after birth is unlikely to contribute substantially to the risk of childhood leukemia in North America.

Acute Disease↗
PubMed1999

Effects of isoproterenol on twitch contraction of wild type and phospholamban-deficient murine ventricular myocardium.

Ablation of the gene for phospholamban (PLB), a transmembrane peptide regulator for the cardiac sarcoplasmic reticulum Ca2+ pump, in mice brings about a complete loss of the myocardial responses to beta-adrenergic agonists (e.g., Luo et al., Circ. Res. 1994; 75: 401). We have evaluated the functional significance of PLB-independent mechanisms in the myocardial responses to beta-adrenergic stimulation in isolated intact ventricular myocardium. We compared the effects of (-)-isoproterenol (ISO) on isometric twitch contraction of paced right ventricular muscle strips of wild type (WT) and PLB-deficient (PLBKO) mice. At 37 degrees C, frequent spontaneous contractions in both types of muscles required the inclusion of lidocaine, an antiarrhythmic, in the bathing medium. Thus the experiments were also performed at two lower temperatures, 30 degrees C and 25 degrees C, at which lidocaine was not needed. Under three conditions, in the absence of ISO, PLBKO ventricular muscles exhibited substantially shortened time to peak tension (TPT) and half relaxation time (TR1/2), compared with the WT muscles. In both WT and PLBKO muscles ISO increased the peak developed tension and decreased TPT and TR1/2 in a dose-dependent manner although the effects were generally smaller in PLBKO than in WT muscles. One micromolar ISO caused TPT and TR1/2 to decrease by 7.3+/-1.2% (mean+/-SEM) and 7.5+/-1.2% in PLBKO vs. 22.8+/-0.7% and 29.1+/-1.7% in WT at 37 degrees C; by 13.5+/-0.4% and 14.1+/-1.2% in PLBKO vs. 31.3+/-0.8%, and 44.8+/-1.3% in WT at 30 degrees C; by 15.0+/-2.3% and 21.1+/-4.9% in PLBKO vs. 25.8+/-1.9% and 54.0+/-1.9% in WT at 25 degrees C. These findings strongly suggest that PLB-independent mechanisms play a significant role in mediating the positive inotropic and lusitropic effects of beta-adrenergic agonists on ventricular myocardium.

Adrenergic Agonists↗
PubMed1999

A diazo-2 study of relaxation mechanisms in frog and barnacle muscle fibres: effects of pH, MgADP, and inorganic phosphate.

The aim of this study was to compare the effects of increased concentrations of MgADP, inorganic phosphate (Pi) and H+ ([MgADP], [Pi] and [H+], respectively) on the rate of relaxation in two different muscle types: skinned muscle fibres from the frog Rana temporaria and myofibrillar bundles from the giant Pacific acorn barnacle Balanus nubilus. Relaxation transients are produced by the photolysis of diazo-2 and are well fitted with a double exponential curve, giving two rate constants: k1 [5.6+/-0.1 s-1 for barnacle, n=30; 26.3+/-0.7 s-1 for frog, n=14 (mean+/-SEM)] and k2 [0.6+/-0.1 s-1 in barnacle, n=30; 10.4+/-1.0 s-1 in frog, n=14 (mean+/-SEM)], at 10 degrees C. Decreasing the pH by 0.5 pH units did not significantly affect k1 for barnacle relaxation [5.6+/-0.1 s-1 (mean+/-SEM), n=15] compared to the decrease in k1 of 40% seen in frog. Use of the Ca2+-sensitive fluorescent label acrylodan on barnacle wild-type troponin C demonstrated that decreasing the pH from 7.0 to 6.6 only alters the pCa50 value by 0.23 in the cuvette, while stopped-flow experiments with acrylodan revealed no significant change in koff from the labelled protein [322+/-32 s-1 at pH 7.0 and 381+/-24 s-1 (mean+/-SEM) at pH 6.6]. Increasing [MgADP] by 20 microM (50 microM added ADP) from control values of 50 microM in frog decreased k1 to 12.3+/-0.4 s-1 (mean+/-SEM, n=8), and at 400 microM MgADP, k1=9.6+/-0.1 s-1 (mean+/-SEM, n=12). In barnacle, 500 microM MgADP had a much smaller effect on k1 (4.0+/-0. 9 s-1, mean+/-SEM, n=8). Increasing the free [Pi] from the contaminant level of 0.36 mM to 1.9 mM slowed k1 by approximately 15% in barnacle [4.8+/-0.8 s-1, mean+/-SEM, n=7], compared to a approximately 30% reduction seen in frog. We conclude that the differences between barnacle and frog seen here are most probably due to different isomers of the contractile proteins, and that events underlying the crossbridge cycle are the same or similar. We interpret our results according to a model of crossbridge transitions during relaxation.

2-Naphthylamine↗
PubMed1999

A novel method of extraction of TnC from skeletal muscle myofibrils.

Incubation of mechanically skinned barnacle myofibrillar bundles in 10 mM orthovanadate (pH 6.6) results in the loss of Ca2+-dependent force generation, which reduces to 0.98+/-0.006% (mean +/-SEM, n=25) of control levels. Analysis of myofibrillar bundles by gel electrophoresis showed that tension loss is primarily due to the extraction of troponin C (TnC) (65.4+/-5.04% mean +/-SEM, n=5). This is a novel finding, since treating cardiac fibres with orthovanadate results in the removal of both TnC and troponin I (TnI) (28). Ca2+ dependence was restored to the myofibrillar bundles following reconstitution with either native isoform of barnacle TnC (BTnC1: 78. 72+/-12.8%, n=9, BTnC2: 82.73+/-20.3%, n=3). The reversible loss of Ca2+-dependent tension generation following the removal and replacement of TnC indicates that the regulation of contraction in the barnacle is controlled by thin-filament regulatory proteins.

Animals↗
PubMed1999

Characterisation of a mutant of barnacle troponin C lacking Ca2+-binding sites at positions II and IV.

This study investigates a mutant barnacle troponin C (TnC) protein (BTnC2-4-) in which the Ca2+-binding sites (sites II and IV) have been rendered non-functional. Eliminating Ca2+ binding at both Ca2+-binding sites of barnacle TnC did not prevent the incorporation of BTnC2-4- into TnC-depleted myofibrillar bundles, although, as expected, the mutant was not able to effect muscle regulation. We conclude that the Mg2+ involved in stabilising the interaction between TnC and TnI in the barnacle must bind at a separate location to the Ca2+-binding sites. Competition experiments between BTnC2-4- and wild-type barnacle TnC (BTnCWT) or the native isoform BTnC2 indicate that BTnC2-4- has an approximately fourfold higher affinity for barnacle TnI than BTnCWT but a lower affinity for TnI compared to BTnC2. These results indicate that disabling sites II and IV changes the affinity of BTnC2-4- for TnC-denuded barnacle myofibrils, altering the stability of the bond formed between TnC and the thin filament.

Animals↗
PubMed1999

The genetic revolution: change and challenge for the dietetics profession.

Advances in genetics are occurring at a pace that challenges our ability to understand and respond to the implications. Soon we will be able to define more precisely the molecular mechanisms underlying human health and disease; subdivide diseases and conditions (e.g., obesity) that are clinically indistinguishable into more distinct entities, thereby improving our ability to choose rational preventive and treatment measures; identify genotypic markers that predict metabolic responses to dietary interventions; stratify the population into groups at higher or lower risk for chronic diseases such as cancer, thus allowing dietary intervention to be appropriately targeted; and develop dietary recommendations that take into account genetically determined taste preferences. Dietetics leaders, teachers, practitioners, and researchers must act now to ensure that dietetics professionals are prepared for practice in this new era. In this article we introduce the Human Genome Project, review the fundamentals of molecular genetics, discuss genetics and disease risk, and define and give examples of diet-gene interactions. We also discuss issues relevant to dietary counseling of healthy people with genetic susceptibility to chronic disease. To foster the growth of knowledge regarding this new biology among dietitians, The American Dietetic Association should take the following steps: require course work on diet-gene interactions and include human genetics as a topic area on dietetic registration examinations, form a practice group on this topic, develop an Internet-based communication and information hub for dietetics professionals, sponsor a session on human genetics at annual meetings, begin a dialogue regarding a new practice specialty in diet and genetic counseling, and encourage a health care system in which personal counseling on diet-gene interactions is valued and reimbursed.

Diet↗
PubMed1999

BAT-26 and BAT-40 instability in colorectal adenomas and carcinomas and germline polymorphisms.

Analysis of the mononucleotide repeats BAT-26 and BAT-40 has reportedly revealed significant microsatellite instability in sporadic colorectal adenomas, whereas studies with dinucleotide and tetranucleotide repeats have not. In addition, BAT-26 has been reported to be "quasimonomorphic" in the germline. We evaluated BAT-26 and BAT-40 in a series of colorectal tumors previously analyzed with a panel of tetranucleotide repeats. Instability in BAT-26 or BAT-40 was significantly associated with tetranucleotide repeat instability in sporadic adenomas and carcinomas (P < 0.0001) and was similarly much less common in adenomas than in carcinomas. Germline polymorphisms in both BAT-40 and BAT-26 were identified, and the frequency of BAT-26 polymorphisms was significantly higher in African Americans than in Caucasians (7.7% versus 0.08%, P < 0.001). BAT-26 and BAT-40 may be very useful in evaluating instability in small tumors, as sufficient DNA to be amplified by large panels of microsatellites is not always available from such lesions. Polymorphisms in these microsatellites, however, limit their utility in determinations of microsatellite instability without corresponding normal DNA.

3-Hydroxysteroid Dehydrogenases↗
PubMed1999

The shape of age-incidence curves of female breast cancer by hormone-receptor status.

OBJECTIVES: Substantial decline of ovarian hormones at menopause plays an important role in breast cancer etiology. Hormones must bind to specific receptors to elicit biological responses, however. We therefore hypothesized and examined whether the age-specific risk of breast cancer, especially its change at menopause, differs by estrogen and progesterone receptor (ER/PR) status. METHODS: Age-specific incidence rates, stratified by ER/PR status, were estimated by multiplying the age-specific ER/PR distribution among 3359 cases in the Danish Breast Cancer Cooperative Group by Danish national age-specific incidence rates. International variations in the age-incidence curve were also reviewed in relation to the hypothesis. RESULTS: The incidence of ER +/PR + subtype (62.9% of all cases) increased with age continually, with a sudden decrease in the rate of increase around age 44. The incidence of ER-/PR- subtype (17.6%) increased with age prior to about age 50 but remained unchanged subsequently. The incidence of ER+ /PR- subtype (13.9%) increased rapidly during the menopausal period but only slightly afterwards. The incidence of ER-/PR+ subtype (5.6%) increased until about age 43 and decreased subsequently. The international comparison revealed Western women, particularly the elderly, might be at substantially higher risk for ER+ /PR+ subtype compared to Japanese women. CONCLUSION: Age-specific risk of breast cancer differs by ER/PR status. The large international variation of breast cancer incidence rates may be explained largely by the risk difference for ER+ /PR+ subtype.

Adult↗
PubMed1999

Hormone replacement therapy and improved survival among postmenopausal women diagnosed with colon cancer (USA).

OBJECTIVES: Hormone replacement therapy (HRT) has been inversely associated with colon cancer incidence in several epidemiologic studies. In this study we used data from a population-based incident case-control study of colon cancer to evaluate the role of HRT use in survival after diagnosis with colon cancer. METHODS: Data from 815 postmenopausal women living in Utah, California, and Minnesota diagnosed between 1 September 1991 and 30 September 1994 were used to examine associations between HRT and survival. RESULTS: After adjusting for age at time of diagnosis, stage of disease at time of diagnosis, study center, and body mass index (BMI), we observed that women who had ever used HRT had a 30% lesser probability of dying of any cause and a 40% lower probability of dying from colon cancer specifically during the follow-up period. Further evaluation by years of HRT use showed that those who had used HRT for 4 or more years had the lowest risk of dying of colon cancer (hazard rate ratio 0.5, 95% confidence interval 0.3-0.9). Evaluation of other lifestyle variables with HRT use did not show significant confounding or effect modification. CONCLUSIONS: These findings suggest that HRT use may improve short-term survival after diagnosis with colon cancer; there is no suggestion that HRT use is detrimental to survival.

Adult↗