Gender differences in attitudes among those at risk for Huntington's disease

This report presents and discusses selected findings regarding gender differences from an Australian-based study that investigated attitudes of individuals at risk for Huntington's disease (HD) towards genetic risk and predictive testing. Clear gender differences emerged regarding perceived coping capacity with regard to predictive testing, as well as disclosure of the genetic risk for HD to others. Female participants were more likely to disclose their genetic risk to others, including their medical practitioners, while male participants were three times more fearful of disclosing their genetic risk to others. These findings are of interest in light of gender differences that have consistently been reported regarding the uptake of predictive testing for HD, other genetic conditions, and health services more generally. While gender differences cannot provide a fully explanatory framework for differential uptake of predictive genetic testing, men and women may experience and respond differently to the genetic risk for HD and possibly other inherited disorders. The meanings of genetic risk to men and women warrants further exploration, given anticipated increases in genetic testing for more common conditions, especially if post-test interventions are possible. These issues are also relevant within the context of individuals' concerns about the potential for discrimination on the basis of genetic risk or genetic test information.     

Experiences of Genetic Risk: Disclosure and the Gendering of Responsibility

The question of ‘who owns genetic information‘ is increasingly a focus of ethical inquiry. Applied to predictive testing, several recent critiques suggest that persons with a genetic disorder have a moral duty to disclose that information to other family members. The justification for this obligation is that genetic information belongs to and may benefit not only a single individual, but also members of a biological kinship. This paper considers this issue from a different vantage point: How does gender intersect with the moral duty to disclose genetic information? Scholars have argued that gender is partly comprised of distinct assignments and assumptions of responsibility. Thus, there is a danger that gendered patterns of socialization will make women feel that they should take primary responsibility for disclosing genetic information to others. This article explores issues of responsibility and disclosure of risk information by drawing on an empirical study of women and men who have undergone genetic testing for hereditary breast/ovarian cancer. The research study suggests that disclosure of genetic information is a gendered activity, with both the benefits and burdens of this task falling primarily on women. It also illustrates that when disclosure is understood contextually, it is a far more complicated matter than when viewed through a theoretical lens. The article considers the relevance of these findings on ethical debate and genetic counselling practices.     

Likelihood of attending bowel screening after a negative genetic test result: the possible influence of health professionals

This study was undertaken to determine the extent to which the reported likelihood of attending future bowel screening following negative genetic testing results for familial adenomatous polyposis (FAP) varies between the type of health professional providing care and the country of testing. The study subjects were 103 unaffected adults at risk for FAP who received negative results following predictive DNA testing. Our study indicates that the reported likelihood of attending bowel screening was higher in those given results by nongenetics physicians, rather than by genetics professionals; the reported likelihood of attending bowel screening under these circumstances was also higher in the UK than in Australia. Both of these results were affected by the perceived chances of developing FAP, and, in the case of the country of testing, by the perceived accuracy of the genetic test result and the perceived seriousness of the disease. How and what health professionals communicate with patients about genetic testing may explain the differences between type of health professional and country of testing and attitudes toward bowel screening. If this is the case, training in communication may change patients' perceptions and, in turn, their behavioral intentions and actions following a negative test result.     

Using the optimal receiver operating characteristic curve to design a predictive genetic test, exemplified with type 2 diabetes

Current extensive genetic research into common complex diseases, especially with the completion of genome-wide association studies, is bringing to light many novel genetic risk loci. These new discoveries, along with previously known genetic risk variants, offer an important opportunity for researchers to improve health care. We describe a method of quick evaluation of these new findings for potential clinical practice by designing a new predictive genetic test, estimating its classification accuracy, and determining the sample size required for the verification of this accuracy. The proposed predictive test is asymptotically more powerful than tests built on any other existing method and can be extended to scenarios where loci are linked or interact. We illustrate the approach for the case of type 2 diabetes. We incorporate recently discovered risk factors into the proposed test and find a potentially better predictive genetic test. The area under the receiver operating characteristic (ROC) curve (AUC) of the proposed test is estimated to be higher (AUC = 0.671) than for the existing test (AUC = 0.580).     

'You don't make genetic test decisions from one day to the next'--using time to preserve moral space

The part played by time in ethics is often taken for granted, yet time is essential to moral decision making. This paper looks at time in ethical decisions about having a genetic test. We use a patient-centred approach, combining empirical research methods with normative ethical analysis to investigate the patients' experience of time in (i) prenatal testing of a foetus for a genetic condition, (ii) predictive or diagnostic testing for breast and colon cancer, or (iii) testing for Huntington's disease (HD). We found that participants often manipulated their experience of time, either using a stepwise process of microdecisions to extend it or, under the time pressure of pregnancy, changing their temporal 'depth of field'. We discuss the implications of these strategies for normative concepts of moral agency, and for clinical ethics.     

Sex-Based Differences in Cardiac Arrhythmias, ICD Utilisation and Cardiac Resynchronisation Therapy

Many important differences in the presentation and clinical course of cardiac arrhythmias are present between men and women that should be accounted for in clinical practice. In this paper, we review published data on gender differences in cardiac excitable properties, supraventricular tachycardias, ventricular tachycardias, sudden cardiac death, and the utilisation of implantable defibrillators and cardiac resynchronisation therapy. Women have a higher heart rate at rest, and a longer QT interval than men. They further have a narrower QRS complex and lower QRS voltages on the 12-lead ECG with more often non-specific repolarisation abnormalities at rest. Supraventricular tachycardias, such as AV nodal reentrant tachycardia, are twice as frequent in women compared with men. Atrial fibrillation, however, has a 1.5-fold higher prevalence in men. The triggers for idiopathic right ventricular outflow tract tachycardia (VT) initiation are gender specific, i.e. hormonal changes play an important role in the occurrence of these VTs in women. There are clear-cut gender differences in acquired and congenital LQTS. Brugada syndrome affects men more commonly and severely than women. Sudden cardiac death is less prevalent in women at all ages and occurs 10 years later in women than in men. This may be related to the later onset of clinically manifest coronary heart disease in women. Among patients who receive ICDs and CRT devices, women appear to be under-represented, while they may benefit even more from these novel therapies.     

Livestock production,age, and gender among the Keiyo of Kenya

This article is based on a study of time allocation and decision making patterns among the Keiyo in three ecological zones of Elgeyo-Marakvet District, Kenya. It finds that age and gender are important factors to consider when examining livestock production among African smallholder farmers. This is especially true where males are absent from home for wage labor. In these situations women, young males between the ages of 6–15, and persons of both sexes aged 65 and over spend considerable amounts of time engaged in livestock-related activities. These women are also more actively involved in decision making concerning the marketing of milk. The results indicate that there is a definite need to consider the contributions of these other persons when efforts are being made to improve elements of the livestock sector.     

Gender differences and the interpretation of genetic instability in Alzheimer's disease.

The neuronal degeneration and death which characterize Alzheimer's disease (AD) may stem from a constitutive genetic instability related to DNA repair deficits. To test this hypothesis, we treated peripheral blood lymphocytes from persons with AD, age-matched controls, and young controls with two drugs that induce chromosome breakage. Bleomycin, a radiomimetic antineoplastic drug, causes single- and double-stranded DNA breaks through the generation of activated oxygen radicals. Methyl methane-sulfonate (MMS) is a monofunctional alkylating agent that binds covalently to DNA. Cells were grown in culture for 72 h, with drug treatments for 4 h (bleomycin) or 24 h (MMS) prior to harvest. Fifty cells per subject per drug were scored for chromosome breakage. Breakage rates for both drugs in AD women were significantly higher than those in age-matched control women. This was not the case in men, due to the very high induced breakage rates seen in the age-matched normal control men. Because the induced breakage rates in AD women and AD men are equivalent, it seems likely that an independent factor may be contributing to genetic instability in the normal control men. Our findings indicate that the interpretation of the response of AD lymphocyte chromosomes to DNA-damaging chemicals can be strongly confounded by the effects of gender ratio in the control population sampled. These findings have important implications for the design of future studies of Alzheimer's disease, as well as for the assessment of health risks in unaffected elderly populations.     

A projection of benefits due to fecal occult blood test for colorectal cancer

Objectives: A prospective study to estimate benefits due to fecal occult blood tests for colorectal cancer are carried out for both males and females, under different screening frequencies. Methods: We apply the statistical method developed by Wu et al. (2007) [1] using the Minnesota colorectal cancer study group data, to make Bayesian inference for the lead time, the time of diagnosis advanced by screening for both male and female participants in a periodic screening program. The lead time is distributed as a mixture of a point mass at zero and a piecewise continuous distribution. The two parts of the mixture correspond to two aspects of the screening: the probability of no benefit, or the percentage of interval cases; and the probability distribution of the early diagnosis time. We present estimates of these two measures for males and females by simulation studies using the Minnesota study group data. We also provide the mean, mode, variance, and density curve of the program's lead time by gender. This may provide policy makers important information on the effectiveness of the FOBT screening in colorectal cancer early detection. Results: The mean lead time increases as the screening time interval decreases for both males and females. The standard error of the lead time also increases as the screening time interval decreases for both genders. Females seem get more benefit than males, in that females usually have a longer lead time than males if both take the test at the same time interval and the lead time mode for females is greater than that of males in the same screening time interval. Conclusion: According to the predictive estimation of the lead time distribution, to guarantee a 90% chance of early detection, it seems necessary for the males to take the fecal occult blood test every 9 months, while the females can take it annually.     

Non-uptake of predictive genetic testing for BRCA1/2 among relatives of known carriers: attributes, cancer worry, and barriers to testing in a multicenter clinical cohort

BRCA1/2 test decliners/deferrers have received almost no attention in the literature and this is the first study of this population in the United Kingdom. The aim of this multicenter study is to examine the attributes of a group of individuals offered predictive genetic testing for breast/ovarian cancer predisposition who did not wish to proceed with testing at the time of entry into this study. This forms part of a larger study involving 9 U.K. centers investigating the psychosocial impact of predictive genetic testing for BRCA1/2. Cancer worry and reasons for declining or deferring BRCA1/2 predictive genetic testing were evaluated by questionnaire following genetic counseling. A total of 34 individuals declined the offer of predictive genetic testing. Compared to the national cohort of test acceptors, test decliners are significantly younger. Female test decliners have lower levels of cancer worry than female test acceptors. Barriers to testing include apprehension about the result, traveling to the genetics clinic, and taking time away from work/family. Women are more likely than men to worry about receiving less screening if found not to be a carrier. The findings do not indicate that healthy BRCA1/2 test decliners are a more vulnerable group in terms of cancer worry. However, barriers to testing need to be discussed in genetic counseling.     

The transmission/disequilibrium test: history, subdivision, and admixture.

Disease association with a genetic marker is often taken as a preliminary indication of linkage with disease susceptibility. However, population subdivision and admixture may lead to disease association even in the absence of linkage. In a previous paper, we described a test for linkage (and linkage disequilibrium) between a genetic marker and disease susceptibility; linkage is detected by this test only if association is also present. This transmission/disequilibrium test (TDT) is carried out with data on transmission of marker alleles from parents heterozygous for the marker to affected offspring. The TDT is a valid test for linkage and association, even when the association is caused by population subdivision and admixture. In the previous paper, we did not explicitly consider the effect of recent history on population structure. Here we extend the previous results by examining in detail the effects of subdivision and admixture, viewed as processes in population history. We describe two models for these processes. For both models, we analyze the properties of (a) the TDT as a test for linkage (and association) between marker and disease and (b) the conventional contingency statistic used with family data to test for population association. We show that the contingency test statistic does not have a chi 2 distribution if subdivision or admixture is present. In contrast, the TDT remains a valid chi 2 statistic for the linkage hypothesis, regardless of population history.     

Predictive testing for hereditary nonpolyposis colorectal cancer: subjective perception regarding colorectal and endometrial cancer, distress, and health-related behavior at one year post-test

This study evaluated illness representations, distress, and health-related behavior one year after disclosure of a predictive genetic test result for hereditary nonpolyposis colorectal cancer (HNPCC) in 36 carriers and 36 noncarriers. Post-test, no significant differences between carriers and noncarriers were found in perceived risk and perceived seriousness of colorectal and endometrial cancer or in perceived control over endometrial cancer. Confidence in the controllability of colorectal cancer by means of medical examinations was higher for carriers than noncarriers post-test. Mean levels of distress (cancer-specific distress, state anxiety, psychoneuroticism) were within normal ranges and none of the participants had an overall pattern (on all scales) of clinically elevated levels of distress. Carriers had significantly higher cancer-related distress one year posttest than noncarriers. In both groups, colorectal cancer-related distress decreased. Noncarriers additionally showed decreased endometrial cancer-related distress and state anxiety. Within the year after testing, none of the noncarriers had a colonoscopy and all carriers where adherent to the recommendations regarding colorectal cancer screening. Although interview data delineated individually different problems specifically related to predictive testing (e.g., worry, difficulties in relation to other relatives, burden of regular follow-up), generally, predictive testing for HNPCC does not seem to induce major psychological problems. Moreover, the presented data are promising regarding the impact on health-related behavior.     

A Comparison of Podocyturia,Albuminuria and Nephrinuria in Predicting the Development of Preeclampsia: A Prospective Study

Preeclampsia, a hypertensive multisystem disease that complicates 5–8% of all pregnancy, is a major cause for maternal and fetal mortality and morbidity. The disease is associated with increased spontaneous and evoked preterm birth and remote cardio-renal disorders in the mother and offspring. Thus the ability to predict the disease should lead to earlier care and decreased morbidity. This has led to fervent attempts to identify early predictive biomarkers and research endeavors that have expanded as we learn more regarding possible causes of the disease. As preeclampsia is associated with specific renal pathology including podocyte injury, early urinary podocyte (podocyturia), or the podocyte specific proteinuria nephrin in the urine (nephrinuria), as well as the more easily measured urinary albumin (albuminuria), have all been suggested as predictive markers. We performed a prospective study recruiting 91 pregnant women (78 of whom were high risk) and studied the predictive ability of these three urinary biomarkers. The subjects were recruited between 15–38 weeks of gestation. Fourteen patients, all in the high-risk obstetric group, developed preeclampsia. The levels of podocyturia, nephrinuria, and albuminuria were variably higher in the high-risk pregnant patients who developed preeclampsia. The sensitivities and specificities for podocyturia were 70% and 43%, for albuminuria were 36% and 96%, and for nephrinuria were 57% and 58%, respectively. Also, abnormal nephrinuria (69%) and podocyturia (38%) were detected in low risk women who had uncomplicated gestations; none of these women exhibited albuminuria. In our study, none of the three urinary markers achieved the minimum predictive values required for clinical testing. The lack of excessive albuminuria, however, may indicate a preeclampsia-free gestation. Given a discrepant literature, further studies with larger sample size should be considered.     

Size,gender, and sex change in dwarf ginseng,Panax trifolium (Araliaceae)

Summary Flowering individuals of dwarf ginseng may be either male or hermaphroditic. I recorded the sex expression and size of individuals in three populations for three or four years in order to 1) determine whether this bimodal distribution of sex expression was due to sex changing or genetic dimorphism, and 2) test predictions about a) the relationship between size and gender, and b) the association of size change and sex change. Twenty five to 37% of the flowering individuals in each population changed gender from one year to the next. Of the plants I followed for four years, 83% changed sex and 57% changed more than once. In each of these populations as well as two others, hermaphrodites were significantly larger than males. Gender dynamics of the three populations differed, but hermaphrodites tended to become smaller and were more likely to change gender than remain hermaphroditic the following year, whereas males tended to grow larger and were more likely to remain male than to change gender. Dwarf ginseng is clearly a diphasic (sex changing) species in which sex expression is determined primarily by size. A difference between genders in the immediate resource costs of reproduction appears to be an important determinant of sex change and gender phase ratios in populations.     

Validity and cost-effectiveness of the Gonozyme test in the diagnosis of gonorrhea.

Although bacterial culture is considered to provide the most definitive diagnosis of gonorrhea, it has limitations when specimens must be transported long distances. A study was carried out to evaluate the validity and cost-effectiveness of an alternative method of diagnosing gonorrhea, the Gonozyme test, a commercially available enzyme immunoassay. Urogenital specimens from 100 men and 100 women with symptoms suggestive of or a history of exposure to gonorrhea were tested for the presence of Neisseria gonorrhoeae by means of bacterial culture and for gonococcal antigen with the Gonozyme test. The specimens from the men were also examined by means of microscopy of Gram-stained smears. The sensitivity and specificity of the Gonozyme test with reference to culture results were 95.6% and 97.4% respectively in the men and 84.2% and 98.7% in the women. The predictive value of a positive result was 91.6% in the men and 94.1% in the women, and the predictive value of a negative result 98.6% in the men and 96.3% in the women. The cost-effectiveness of the Gonozyme test was higher than that of bacterial culture in this population, which had a high prevalence rate of gonorrhea (23% in the men and 19% in the women). The Gonozyme test would be an adequate alternative to culture for the diagnosis of gonorrhea and contact tracing in areas far from diagnostic laboratories.     

Patterns of child fosterage in rural northern Thailand

Evolutionary theory guides an investigation of foster parent selection in two northern Thai villages with different biosocial environments: one village has high levels of labour migration and divorce, and growing numbers of parental death due to HIV/AIDS, while the other village has lower migration, divorce and parental mortality levels. Focus groups examine mothers' and fathers' motivations and ideals regarding foster caretaker selection, and quantitative family surveys examine real fostering outcomes: specifically, the laterality (matrilateral versus patrilateral) and genetic distance of the foster caretakers of all ever-fostered children in these two villages. As predicted, in environments of high marital stability and paternity certainty, parents seem to prefer close genetic kin from either side as foster parents for their children. In low marital stability and paternity certainty environments, parents trust their own lateral kin, regardless of genetic distance, over close genetic kin from the other side. The striking exception to this pattern, however, occurs in the case of parental death, in which case children are fostered to the deceased parent's kin, regardless of the child's sex or other factors. In general, the foster parents for girls are selected with more care, reflecting the daughter/female preference expected in traditionally matrilineal, matrilocal societies. An ordered decision-making pathway for foster parent selection is proposed, taking into consideration the key factors of (a) the circumstances driving the fostering decision, (b) the gender of the child, (c) the gender of the key decision-making parent, and (d) the degree of marital and population fluidity (and subsequent, paternity certainty) in the village.     

Maternal waist-to-hip ratio does not predict child gender

It has been suggested that a high pre-conceptual waist-to-hip ratio (WHR) is a good predictor of male offspring and, thus, in cultures that value male children, an androgenous body shape may be judged as most attractive. The predictive value of WHRs is based on studies measuring women who already have children and correlating their WHRs with the proportion of existing male offspring. However, carrying a male child may alter WHRs in a different way to carrying a female child, and a high WHR may be an effect rather than a cause of male offspring. In order to test the predictive power of a pre-conceptual WHR and offspring gender, we took WHR measures from 458 women who intended to become pregnant and then correlated this with the genders of their subsequent children. We found no significant correlation. It is therefore not clear why a high WHR is preferred in some cultures. We suggest that differences in attractiveness preferences between different ethic groups are actually based on weight scaled for height (the body mass index or BMI) rather than the WHR since although there will be a preferred optimal BMI for each ethnic group, which will balance environmental and health factors, this optimal BMI may differ between groups and environments.     

Type 2 diabetes, impaired glucose tolerance, and hypertension in offspring of migrants and the structure of the population of origin

Data collected from Nisei men and women, offspring of immigrants to the United States from Japan, were examined for evidence of possible genetic heterogeneity in Japan with respect to type 2 diabetes or non-insulin-dependent diabetes mellitus (NIDDM), impaired glucose tolerance (IGT), and hypertension. The subjects were 391 men and women with a mean age of 62.0 (+/- 0.3) years. Patterns of disease expression in the Nisei with respect to the origins in Japan of their parents indicated that the genetic basis for NIDDM may be more frequent in northern Honshu than in southwestern Honshu, whereas that for IGT may be more frequent in southwestern Honshu. Further analyses indicate that the pattern for IGT is restricted to men. Hypertension appears more frequently in persons with parents from northern Honshu and less frequently in women but not in men from southwestern Honshu. For men an analysis of age and family history of diabetes by oral glucose diagnostic category revealed the presence of a group of younger men with IGT but, surprisingly, no family history of diabetes. Thus the data show an apparent lack of the consistency expected if diabetes and IGT simply represent stages of one disease entity. We suggest that IGT may represent a heterogeneous category including both an early or transitional stage of NIDDM and another condition found primarily in men in which less severe glucose tolerance appears and with which hypertension may be associated. Data on ancient settlement in Japan suggest a possible historical basis for the patterns found.     

Acetic acid test: a promising screening test for early detection of cervical cancer

OBJECTIVE: To determine whether the acetic acid test (AAT) could be used as a screening testfor early detection of cervical cancer. STUDY DESIGN: A hospital-based study was carried out. A sample of 376 women who attended the early cancer detection program of the Instituto Mexicano del Seguro Social in the state of Durango during 1998 was included. The AAT was applied during the gynecologic examination. Each women underwent colposcopy and directed cervical biopsy. RESULTS: The biopsies revealed that five women had cervical intraepithelial neoplasia grade 1 (CIN 1) and 51, 2/3. Four values (true positive,false positive, false negative and true negative) were obtained according to the pathologic test for CIN 1(5, 129, 0 and 191) andfor CIN 2/3 (47, 129, 4 and 191). Sensitivity, specificity, negative predictive value and positive predictive value in women with CIN 1 were 1.00, .60, 1.00 and .04 and with CIN 2/3 were .92, .60, .98 and .27, respectively. CONCLUSION: This test is promisingfor early detection of cervical cancer given its high sensitivity. Understanding the biologic mechanisms underlying acetowhite changes necessitates further studies.     

Allomaternal Investment and Relational Uncertainty among Ngandu Farmers of the Central African Republic

Several studies have suggested a matrilateral bias in allomaternal (non-maternal) infant and child caregiving. The bias has been associated with the allomother’s certainty of genetic relatedness, where allomothers with high certainty of genetic relatedness will invest more in children because of potential fitness benefits. Using quantitative behavioral observations collected on Ngandu 8- to 12-month-old infants from the Central African Republic, I examine who is caring for infants and test whether certainty of genetic relatedness may influence investment by allomothers. Results indicate a matrilateral bias in caregiving by extended kin members, but this does not affect the total level of care infants receive when fathers and siblings are included in the analysis. These results replicate a previous study done among an adjacent foraging population and emphasize the importance of examining children’s complete social environments when addressing caregiving and child development.