Population Differences In Risk Research Articles

USING PARTICIPATORY METHODS AND GEOGRAPHIC INFORMATION SYSTEMS (GIS) TO PREPARE FOR AN HIV COMMUNITY-BASED TRIAL IN VULINDLELA, SOUTH AFRICA (Project Accept-HPTN 043).

Recent attempts to integrate geographic information systems (GIS) and participatory techniques, have given rise to terminologies such as participatory GIS and community-integrated GIS. Although GIS was initially developed for physical geographic application, it can be used for the management and analysis of health and health care data. Geographic information systems, combined with participatory methodology, have facilitated the analysis of access to health facilities and disease risk in different populations. Little has been published about the usefulness of combining participatory methodologies and GIS technology in an effort to understand and inform community-based intervention studies, especially in the context of HIV. This article attempts to address this perceived gap in the literature. The authors describe the application of participatory research methods with GIS in the formative phase of a multisite community-based social mobilization trial, using voluntary counseling and testing and post-test support as the intervention.

Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21

In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.

Pharmacokinetics/Genotype Associations for Major Cytochrome P450 Enzymes in Native and First- and Third-generation Japanese Populations: Comparison With Korean, Chinese, and Caucasian Populations

Application of foreign clinical data across geographic regions can accelerate drug development. Drug disposition can be variable, and identification of factors influencing responsible pharmacokinetic/pharmacogenomic approaches could facilitate the universal application of foreign data and reduce the total amount of phase III clinical trials evaluating risks in different populations. Our objective was to establish and compare genotype (major cytochrome P450 (CYP) enzymes)/phenotype associations for Japanese (native and first- and third-generation Japanese living abroad), Caucasian, Chinese, and Korean populations using a standard drug panel. The mean metabolic ratios (MRs) for the four ethnic groups were similar except for a lower activity of CYP2D6 in Caucasians and CYP2C19 in Asians. Genotype, not ethnicity, impacted the MR for CYP2C9, CYP2C19, and CYP2D6; neither affected CYP1A2, CYP2E1, and CYP3A4/5 activities. We conclude that equivalent plasma drug concentrations and metabolic profiles can be expected for native Japanese, first- and third-generation Japanese, Koreans, and Chinese for compounds handled through these six CYP enzymes.

Visceral Fat, Waist Circumference, and BMI: Impact of Race/ethnicity

BMI and waist circumference are used to define risk from excess body fat. Limited data in women suggest that there may be racial/ethnic differences in visceral adipose tissue (VAT) at a given BMI or waist circumference. This study tested the hypothesis that racial/ethnic differences exist in both men and women in the relationship of anthropometric measures of body composition and computed tomography (CT)-determined VAT or subcutaneous adipose tissue (SAT). Subjects included 66 African American, 72 Hispanic, and 47 white men and women, aged > or =45. Waist circumference and BMI were measured using standard methods. Total abdominal and L4L5 VAT and SAT were measured using CT. Among both men and women, groups did not differ in waist circumference or BMI. White men had greater L4L5 VAT than African-American men, and both white and Hispanic men had greater total VAT than African-American men. Among women, Hispanics and whites had greater L4L5 VAT than African Americans, and Hispanics had greater total VAT than African Americans. The slope of the linear relationship between BMI or waist circumference and VAT was lower in African Americans than in Hispanics and/or whites. Middle-aged and older African-American men and women had lower VAT despite similar BMI and waist circumference measurements. Altered relationships between anthropometric measures and VAT may have implications for defining metabolic risk in different populations. Different waist circumference or BMI cutoff points may be necessary to adequately reflect risk in different racial/ethnic groups.

Systematic Review: Gene Expression Profiling Assays in Early-Stage Breast Cancer

Three gene expression-based prognostic breast cancer tests have been licensed for use. To summarize evidence on the validity and utility of 3 gene expression-based prognostic breast cancer tests: Oncotype DX (Genomic Health, Redwood City, California), MammaPrint (Agendia BV, Amsterdam, the Netherlands), and H/I (AvariaDX, Carlsbad, California). MEDLINE, EMBASE, and Cochrane databases (from 1990 through January 2007), Web sites of test manufacturers, and discussion with the manufacturers. Original data studies published in English that addressed prognostic accuracy and discrimination or treatment benefit prediction of any of the 3 tests in women with breast cancer. Information was extracted about the clinical characteristics of the study population (particularly clinical and therapeutic homogeneity), tumor characteristics, and whether the marketed test or underlying signature was evaluated. The tests are based on distinct gene lists, using 2 different technologies. Overall, the body of evidence showed that this new generation of tests may improve prognostic and therapeutic prediction, but the tests are at different stages of development. Evidence shows that the tests offer clinically relevant, improved risk stratification over standard predictors. Oncotype DX has the strongest evidence, closely followed by MammaPrint and H/I (which is still maturing). For all tests, the relationship of predicted to observed risk in different populations and their incremental contribution over conventional predictors, optimal implementation, and relevance to patients receiving current therapies need further study. Gene expression technologies show great promise to improve predictions of prognosis and treatment benefit for women with early-stage breast cancer. More information is needed on the extent of improvement in prediction, characteristics of women in whom the tests should be used, and how best to incorporate test results into decision making about breast cancer treatment.

Challenges in obesity epidemiology

This paper was commissioned by the Foresight programme of the Office of Science and Innovation, Department of Trade and Industry © 2007 Queen’s Printer and Controller of HMSO; published with permission Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1) , 1–11 1 obesity reviews (2007) 8 (Suppl. 1) , 1–11 OnlineOpen: This article is available free online at www.blackwell-synergy.com Blackwell Publishing LtdOxford, UKOBRObesity Reviews1467-7881© 2007 Queen’s Printer and Controller of HMSO; published with permission; Journal compilation © 2007 The International Association for the Study of Obesity ? 20078 ••111Review Article Challenges in obesity epidemiology D. Canoy & I. Buchan

South Indian men with reduced CAG repeat length in the androgen receptor gene have an increased risk of prostate cancer

The androgen receptor (AR) gene possesses polymorphic CAG tandem repeats and the repeat length has been inversely related to the risk of prostate cancer (PCa). The distinct ethnic variation in the CAG repeat length may be correlated to differences in PCa risk in different populations. To evaluate the CAG repeat length in the AR gene and the implications for PCa, we screened 87 PCa patients and 120 control subjects from South India. The mean CAG repeat length in PCa patients was significantly smaller than that of controls (17.0 vs 20.7; P < 0.001). Men with < or = 19 CAG repeats had a significantly increased risk of cancer compared to those with >19 CAG repeats (age-adjusted OR = 7.01; 95% CI = 3.52-13.94; P < 0.001). However, no significant association was observed between CAG repeats and age of onset or prostate-specific antigen levels. Although there was a trend towards shorter CAG repeat length in high grades of cancer, it was not significant (P = 0.085). Thus, our results suggest an association between short CAG repeats in the AR gene and PCa risk in South Indian men. Further, we propose that CAG repeats could be used as a prognostic marker for PCa diagnosis.

Is reduced CAG repeat length in androgen receptor gene associated with risk of prostate cancer in Indian population?

Shorter CAG repeats in androgen receptor (AR) gene have been found to be associated with an increased risk of prostate cancer (CaP). Ethnic variations in CAG repeat length may contribute to varying risks in different populations. To evaluate the prognostic significance of androgen receptor (AR) CAG repeats in Indian population for CaP, genomic DNA from 113 CaP, 57 benign prostate hyperplasia (BPH) patients and 133 normal healthy controls were examined by using a PCR-based GeneScan analysis. The mean number of CAG repeat in CaP was significantly lower as compared to the healthy controls (20.26 vs 22.98; p = 0.016). The odds ratio for CaP was 2.96 (p < 0.01), when individuals with short CAG repeat (< or =22) were compared with those having longer repeats (>22). A significant association was also observed between short CAG repeat and young age at diagnosis (OR 2.18; p = 0.04). The mean CAG repeat was not significantly different in BPH and healthy controls; however, BPH patients showed a tendency towards short CAG repeats. Thus, our results show that CAG repeat polymorphism in AR gene is significantly associated with CaP risk, suggesting that AR CAG polymorphism may act as a risk modifier to CaP in Indian population.

Nouvelles méthodes d’étude du risque médicamenteux : l’expérience du Centre Midi-Pyrénées de Pharmacovigilance

This review examines the methods used to study adverse drug reactions (ADRs) and to quantify drug risk in pharmacovigilance. Beside analysis of spontaneous reports (the basic and universal alert method in pharmacovigilance), epidemiological methods can also be used. Classical methods are based on intensive recording, case-control or cohort studies, and clinical trials. Other more recent methods have been applied to pharmacovigilance. Using recent personal data, the authors present and discuss these new methods. Case/non-case studies quantify drug risk based on a pharmacovigilance database, and are used as signals in pharmacovigilance. Analysis of laboratory data can also be used to evaluate biological ADRs such as elevated liver enzyme and creatine phosphokinase levels. Cross-linkage studies can be used to minimize the consequences of under-notification in pharmacovigilance. Finally, ADR perception analysis is a useful method to evaluate the perceived social and medical importance of drug risks in different populations (public, pharmacists, general practitioners, medical specialists).

Six reasons why the waist-to-height ratio is a rapid and effective global indicator for health risks of obesity and how its use could simplify the international public health message on obesity

We suggest that a simple, rapid screening tool—the waist-to-height ratio (WHTR)—could help to overcome debates about the use of different body mass index (BMI) boundary values for assessing health risks in different populations. There are six reasons for our proposal:WHTR is more sensitive than BMI as an early warning of health risks.WHTR is cheaper and easier to measure and calculate than BMI.A boundary value of WHTR = 0.5 indicates increased risk for men and women.A boundary value of WHTR = 0.5 indicates increased risk for people in different ethnic groups.WHTR boundary values can be converted into a consumer-friendly chart.WHTR may allow the same boundary values for children and adults.Communicating messages about health risk could be much simpler if the same anthropometric index and the same public health message can be used throughout childhood, into adult life, and throughout the world. This simple message is: Keep your waist circumference to less than half your height.

An update on the genetics of colorectal cancer.

Colorectal carcinoma (CRC) remains a frequent cause of cancer-associated mortality in the UK and still has a relatively poor outcome. Single gene defects account for up to 2-6% of cases, but twin studies suggest a hereditary component in 35%. CRC represents a paradigm for cancer genetics. Almost all the major-gene influences on CRC have been identified, and the identification of the remaining susceptibility alleles is proving troublesome. Only a few low-penetrance alleles, such as methylene tetrahydrofolate reductase C677T, appear convincingly to be associated with CRC risk. To identify the remaining CRC genes, parallel approaches, including strategies based on linkage and association and complementary analyses such as searches for modifier genes, must be employed. To gain sufficient evidence to prove that a gene is involved in CRC predisposition, it is probably necessary for multiple, adequately-powered studies to demonstrate an association with the disease, especially if the allelic variants have only a small differential effect on risk. It may also be possible to show how genes interact with each other and the environment, although this will be even more difficult. Accurate quantitation of the allele-specific risks in different populations will be necessary, but problematic, especially if those risks combine in a fashion which is not of a straightforward additive or multiplicative type. Without any good prior evidence of the nature of the remaining genetic influence on CRC, the possibility remains that this is a truly polygenic trait or that multiple, rare variants contribute to the increased risk; in these cases, identification of the genes involved will be very difficult. Despite these potential problems, the effectiveness of preventive measures for CRC, especially in high-risk individuals, means that the search for new predisposition genes is justified.

Spontaneous micronucleus frequencies in human peripheral Mood lymphocytes as a screening test for an individual variation in a different population and radiation-induced micronucleus induction

Our studies were to evaluate the role of epigenetic factors in the variation of radios ens itivity on human peripheral blood lymphocytes by measuring the frequencies of micronucleus (MN) from 293 healthy subjects of different population for assessing the radiation health risk in Korea. We analyzed the frequencies of both spontaneous and in vitro 60Co y-rays or 50MeV neutron-induced MNs. The frequencies of spontaneous MNs not only vary greatly between individuals, but also working or living areas. The increased levels of cells with spontaneous MNs were observed with an increasing age. The frequencies of spontaneous MNs were significantly higher in females than in males. For both sexes, MN frequency was significantly and positively correlated with age. Age and gender are the most important demographic variables impacting on the MN index. Donors who had ever smoked showed significantly increased frequencies of MNs compared to nonsmokers. The main lifestyle factors influencing the MN index in the subjects are correlated significantly and positively with smoke while measuring the spontaneous frequencies of micronuclei. Therefore, it is evident that with regard to the application of MN assay all future studies to evaluate the association between radiosensitivity and susceptibility for radiation health risks in different populations should take into account the effect of age, gender and lifestyle. For the dose-response study, the induced MNs were observed at all doses, and the numerical changes according to doses. The dose-response curves were fitted with a linear-quadratic forms of the dose, and the results were different for y-rays and neutrons significantly. Neutrons were more effective than y-rays in producing MN with a dose-dependent manner. The frequency of MN varies with dose. The RBE for a micronuclei was 2.37±0.17. The results suggested that the MN assay have a high potential to ensure appropriate quality control and a standard documentation protocol, which can be used to monitor a large population exposed to radiation epidemiologically. We conclude that the determination of individual radiosensitivity with the MN assay is reliable, rapid, sensitive and accurate when used to monitor a large population exposed to radiation.

Assessment of outcomes other than systolic and diastolic blood pressure: pulse pressure, arterial stiffness and heart rate.

In recent years, studies have shown that parameters derived from the arterial pressure wave other than systolic and diastolic blood pressure provide important information on cardiovascular status. Among these parameters, pulse pressure, arterial stiffness and heart rate have emerged as independent markers of cardiovascular risk in different populations. Although a number of studies have used casual measurements of these parameters in a clinic setting, others have focused on their assessment under ambulatory conditions. The pulse pressure represents the amplitude of the pressure wave signal (systolic minus diastolic blood pressure), higher pulse pressure values having been reported in patients possessing cardiovascular risk factors. Close associations between a high pulse pressure and several surrogate end-points have been described. Furthermore, epidemiological studies have shown that a high pulse pressure is an independent predictor of hard end-points in several populations. Arterial stiffness represents one of the major haemodynamic factors determining pulse pressure. Pulse wave velocity, measured from the initial upstroke of the pressure wave, constitutes an established index of arterial stiffness. Studies have reported stiffer arteries in patients with cardiovascular pathology even at an early stage of disease. Close correlations between arterial stiffness and several surrogate markers have been reported, and arterial stiffness and its changes have recently been shown to be an independent predictor of hard end-points in patients with a high cardiovascular risk. Methods to evaluate arterial stiffness under ambulatory conditions are emerging. Heart rate represents the frequency of the cyclical strain of the arterial wall, clinical studies having shown that ambulatory heart rate is correlated to several surrogate markers. A few epidemiological studies have analysed the value of ambulatory heart rate as an independent predictor of hard end-points, but their positive findings need to be confirmed. The analysis of the pressure wave thus allows the determination of several haemodynamic indices other than systolic and diastolic blood pressure. Pulse pressure, arterial stiffness and heart rate constitute other outcomes that may be useful as additional factors in risk assessment for future therapeutic decision-making.

A model for predicting the future incidence of coronary heart disease within percentiles of coronary heart disease risk.

We present a method (The CHD Prevention Model) for modelling the incidence of fatal and nonfatal coronary heart disease (CHD) within various CHD risk percentiles of an adult population. The model provides a relatively simple tool for lifetime risk prediction for subgroups within a population. It allows an estimation of the absolute primary CHD risk in different populations and will help identify subgroups of the adult population where primary CHD prevention is most appropriate and cost-effective. The CHD risk distribution within the Australian population was modelled, based on the prevalence of CHD risk, individual estimates of integrated CHD risk, and current CHD mortality rates. Predicted incidence of first fatal and nonfatal myocardial infarction within CHD risk strata of the Australian population was determined. Approximately 25% of CHD deaths were predicted to occur amongst those in the top 10 percentiles of integrated CHD risk, regardless of age group or gender. It was found that while all causes survival did not differ markedly between percentiles of CHD risk before the ages of around 50-60, event-free survival began visibly to differ about 5 years earlier. The CHD Prevention Model provides a means of predicting future CHD incidence amongst various strata of integrated CHD risk within an adult population. It has significant application both in individual risk counselling and in the identification of subgroups of the population where drug therapy to reduce CHD risk is most cost-effective.

Family history of cancer and risk of colorectal cancer in Italy.

Subjects with a family history of colorectal cancer (CRC) are at increased risk of CRC, but quantification of the risk in different populations, the possible differences in risk according to localization of the cancer and the association of family history of other cancers with CRC risk are still open issues. We have therefore analysed data from a multicentric case-control study conducted in six Italian areas between 1992 and 1996 of 1225 incident cases of colon cancer, 728 cases of rectal cancer and 4154 controls admitted for acute conditions to the same network of hospitals as the cases. Unconditional logistic regression models including terms for gender, age, study centre, years of education and number of siblings were used to estimate the odds ratios (ORs) of CRC according to various aspects of history of CRC and other cancers in first-degree relatives. The OR for family history of CRC was 3.2 (95% confidence interval, CI, 2.5-4.1) for colon cancer and 2.2 (95% CI 1.6-3.1) for rectal cancer. Colon cancer was significantly associated with a family history of stomach (OR 1.4), bone (OR 2.1) and kidney (OR 2.3) cancers, while rectal cancer was significantly associated with a family history of lymphomas (OR 2.8). There was a 30% higher risk of colon and rectal cancer in subjects with a family history of any cancer, excluding intestine. The ORs for family history of CRC were 5.2 for colon and 6.3 for rectum when the proband's age was below 45 years. The ORs were similar when the affected relative was a parent or a sibling and in different strata of age of relative(s). For subjects with two or more first-degree relatives with CRC, the risk was 6.9 for the right colon, 5.8 for the transverse and descending colon, 3.8 for the sigma, 3.2 for the rectosigmoid junction and 1.9 for the rectum. This study confirms that a family history of CRC in first-degree relatives increases the risk of both colon and rectal cancer, the association being stronger at younger ages and for right colon.

The effects of size-dependent predation risk on the interaction between behavioral and life history traits in a stream-dwelling isopod

In field surveys, laboratory observations and field-based assays of behavior, I examined the effects of size-dependent predation risk on the interaction between size at reproductive maturity and maternal care behavior in the stream-dwelling isopod, Lirceus fontinalis. L. fontinalis exhibit population-specific sizes at reproductive maturity which result in population differences in predation risk during the adult phase. Females from streams containing salamander larvae (that prefer small prey) mature at large sizes and then become relatively safe from predation. Females from streams containing fish (that consume all size classes of prey equally) mature at small sizes and remain at risk. I tested whether these differences in expected survival were reflected in the behavior of females during the maternal phase (i.e., the period during which females exhibit maternal care). Female L. fontinalis carry developing juveniles inside a brood pouch. I simulated predatory attacks on gravid female L. fontinalis from the different population types and found that female behavior correlated with population differences in risk. When “attacked”, females from streams with predatory fish (that experience high risk to adult females) released juveniles from the brood pouch, whereas females from populations with predatory salamander larvae (that pose relatively little risk to adult females) did not release juveniles. I discuss the results with reference to the joint evolution of behavioral and life history traits.