Communication about carrier testing within hemophilia A families

Background

Research describing the communication of genetic information within families is limited. The research that is available encompasses a variety of diseases. Furthermore, some studies report the discussion of risk information among family members, some focus on communicating carrier test results, while others focus on discussion of the genetic aspects of the diseases themselves. This makes it difficult to generalize about family genetic testing communication patterns and practices.

Research suggests that discussion of genetic information within families is likely influenced by a number of factors. While examining public interest in genetic testing for colon cancer susceptibility, Smith and Croyle [1995] asked respondents to consider the hypothetical situation of testing positive for a gene associated with colon cancer. Respondents without health insurance and those who were widowed were least likely to indicate that they would share their test result with family members. Smith and Croyle [1995] argue that widowed individuals may be less likely to share test results because they may have fewer individuals with whom to share the information. Those without insurance may be less likely to share results due to concerns about obtaining insurance in the future. The majority of respondents reported that they would first talk either to a physician or to their spouse about receiving a positive test result. Respondents reporting a family history of colon cancer would be more likely to discuss their test result first with a physician than those not reporting a family history of colon cancer. Smith and Croyle [1995] speculate that those with a family history of colon cancer may be more familiar with the disease and thus may see test results more as a personal medical problem than as something requiring communication with family members.

Several studies assess the discussion of genetic information within the family. Denayer et al. [1990] found that 80% of the parents of a child with cystic fibrosis (CF) informed their brothers and sisters about the genetic aspect of CF. Another study focusing on CF found that only one-third of the siblings of CF patients had disclosed their carrier test results to other unaffected brothers and sisters [Fanos and Johnson, 1995]. Though discussion of genetic information within families is occurring, communication of genetic test results to relatives is not universal within families and seems to be influenced, at least in part, by the genetics of the particular disease involved. For example, higher rates of communicating breast/ovarian genetic test results to female than male relatives have been observed [Green et al., 1997; Hughes et al., 1999]. Women at risk of carrying the hemophilia A gene indicated that they discussed issues related to hemophilia more often with sisters than with brothers [Varekamp et al., 1992].

Evidence that individuals do not always share information about genetic risk with other family members has been found in three studies involving inherited balanced translocations. Suslak et al. [1985] found that 20% of the first-degree relatives of balanced translocation carriers had not been informed of their risk of being a carrier. Wolff et al. [1989] report that families with an affected child or relative shared genetic risk information with family members more often than families in which the adverse effects of an unbalanced karyotype was not as apparent. Ayme et al. [1993] assessed the diffusion of genetic information within families by evaluating which relatives of carriers of a balanced chromosomal abnormality had received genetic testing. Rather than asking carriers with whom they had shared risk information, the authors evaluated karyotyping rates of at-risk relatives. They found that 44% of the at-risk relatives had been tested. In 63.2% of the families, less than half of the at-risk relatives had been karyotyped.

Researchers are extending the study of communication of genetic information within families to include psychological effects. Lerman et al. [1998] found that BRCA1/2 carriers who communicated their test results to their sisters exhibited a small decrease in psychological distress, while carriers who did not disclose their test results showed a small increase in distress. The nature of the genetic tests performed may also affect discussion of test results in families and subsequent psychological effects. For example, individuals undergoing genetic testing for cancer susceptibility may share their test results in part so that other family members can undergo appropriate risk management strategies and screening. The desire to help relatives has been shown to be related to the desire to have genetic testing for colon cancer [Vernon et al., 1999]. Also, the anticipated impact that test results could have on family members has been determined to be an important factor in deciding whether to undergo genetic testing for Huntington disease [Binedell et al., 1998].

A unique aspect of the present study involves examining the extent to which there was discussion of hemophilia A carrier testing before offering DNA-based carrier testing to out study population. A review of the literature revealed one other study assessing family communication before as well as after genetic testing. Green et al. [1997] found that 36 of the 46 women in their study approached at least one other relative for information before going to genetic counseling for breast/ovarian cancer. No woman with a living mother approached any other relative for information, indicating the pivotal role of key informant that mothers played in this sample. After the counseling session, 88% of the women shared their consultation letter with at least one first-degree relative. However, nearly all of the women had at least one first- or second-degree relative whom they were not intending to inform, most commonly due to not being in touch. Interestingly, information was generally revealed during family events, such as family reunions and holiday get-togethers. This was apparently done to avoid alarming family members by contacting them for the sole purpose of sharing cancer risk information.

Research assessing the discussion of genetic information within families affected by hemophilia A is limited. In one study, Varekamp et al. [1992] surveyed female relatives of hemophilia A patients. Respondents revealed that their partners and mothers were the family members with whom they generally discussed the hereditary nature of hemophilia and carrier testing. One out of five women surveyed indicated that the hereditary nature of hemophilia had never been discussed in their parental homes.

Examining the methodologies, research designs, and measurement techniques used in evaluating disclosure of human immunodeficiency virus (HIV infection) status may be informative for researchers exploring communication of genetic carrier test results. Several researchers in the HIV field refer to a process of disclosure. Not only is disclosure of HIV status selective [Leask et al., 1997; Kadushin, 2000], but it occurs in stages. These include adjusting to the diagnosis, assessing one's disclosure skills, deciding whom to tell, and anticipating responses [Kimberly et al., 1995]. There may be similar stages that people undergoing genetic testing go through in communicating test results with relatives. Motivations for disclosure of HIV status [Holt et al., 1998], factors associated with disclosure [Stein et al., 1998], and consequences of disclosure [Mansergh et al., 1995] have been given attention also. HIV status disclosure has been examined for its multiple roles as a stressor, as well as a means of coping with the disease and gaining social support [Cline and Boyd, 1993; Holt et al., 1998]. These factors may also be operative with respect to family communication about genetic testing results.

There are some similarities between HIV and genetic carrier status disclosure. Both HIV and carrier status disclosure may lead to stigmatization within as well as outside the family, such as employment and insurance discrimination. Furthermore, the information provider probably considers the emotional coping ability of those with whom they choose to share the information. An important difference, of course, is there is no risk of transmission involved in genetic diseases, while those who are HIV-positive often reveal their disease status to avoid infecting others, such as health care workers and sexual partners [Cline and Boyd, 1993].

Study Characteristics

The data reported here come from a National Human Genome Research Institute-funded study of hemophilia carrier education, testing, and counseling of at-risk relatives of individuals with hemophilia A (Sorenson, “Hemophilia ‘A’ Carrier Testing: Acceptance and Reactions”). The purpose of this study was to examine the level of interest in and acceptance of direct mutation carrier testing in this population. This study was reviewed and approved by the local institutional review broad. Additionally, a federal writ of confidentiality was obtained to provide added privacy protection for the study populations.

Study Populations

The research involved two populations, patients and their at-risk female relatives.

Patients

Of 127 patients contacted in the clinic, 100 were eligible for study inclusion. Of these, 87 completed the four-page questionnaire. The remainder chose not to participate in the research. Table I presents information about these patients. The majority of patients had severe hemophilia and were not the only one in their family with the disease. Just over two-thirds were Caucasians and just over three-fourths were Protestant. A majority reported an annual income of less than $30,000 per year. Because of the young age of many of these men, a majority had never been married.

Table II presents information on patient's beliefs, attitudes, and prior experience discussing hemophilia in their families. Surprisingly, only 57.9% recalled discussing hemophilia inheritance with someone in the past. About 70% thought their relatives had a low or medium chance of having a child with hemophilia. Nearly 60% had discussed carrier testing with relatives in the past and just over 70% reported an obligation to inform relatives about the study. About 80% reported hemophilia to be a severe or very severe disease. Only four (5.3%) thought our asking them to contact their relatives constituted an invasion of their, their families', or their relatives' privacy.

Relatives

Of 262 at-risk relatives informed about the study by the patient or the patient's mother, 163 (62.2%) agreed to be contacted by the researchers. Of these, 157 (96.9%) were eligible for study inclusion, and of these, 102 (65%) were tested. Ninety-eight of these women completed pre- and posttest questionnaires. These 98 women came from 23 kinships. There was great variability in the number of eligible relatives identified in these kinships, ranging from 1 to 38 eligible relatives. The rate of eligible relative test acceptance within these kinships ranged from 18% to 100%.

Table III presents information on the sociodemographic characteristics of the relatives. Most were married and just under half reported some college or a college degree. The large majority were Caucasians and indicated they were Protestant. Of the 94 relatives reporting household incomes, 38.3% reported an income of less than $30,000 per year and 38.3 reported an income between $30,000 and $50,000 per year. Just over three-fourths were not planning any pregnancies and only 3% were unsure about their reproductive plans.

Table IV reports a variety of relatives' experiences at and prior to the baseline interview. About one-third had had prior non–DNA-based carrier testing and over 80% reported thinking about carrier testing in the past year. Most reported some contact with the patient in the past year and only about one-fifth reported they were not psychologically close to the patient. A majority, 69.1%, reported that relatives had influenced their decision to some degree regarding DNA-based carrier testing. As with the patients, the majority of relatives felt our asking the patients to contact them for this study was not an invasion of their, their relatives', or their families' privacy.

As shown in Table V, mothers were the ones with whom most women reported talking about testing in the year prior to our contacting them, with sisters and the patients' mothers also frequent sources of carrier testing discussion. The discussion of carrier testing with relatives clearly followed gender lines, as one would perhaps expect with an X-linked genetic disease. However, it should be noted that 43.3% reported talking to their relative with hemophilia about carrier testing.

Six months after receiving their test results, relatives were interviewed. They were asked with whom they had discussed their carrier test results (Table VI). Mothers were the family members with whom there was the most test result discussion, followed by partners and sisters. Higher rates of discussion were reported with sisters than with brothers. Additionally, of the 35 relatives with one sister, 71% told her. Of the 30 relatives with one brother, 33% told him. This trend remained in families where there were multiple sisters and brothers. Of the 35 women with more than one sister, 74% told at least one sister while 46% told all their sisters. Of the 25 women with more than one brother, 56% told at least one brother while 28% told all of their brothers. In this population, the communication of DNA-based test results crossed gender lines but still reflected gender differences.

Relatives were also asked whether they were concerned about talking with other relatives, including their own children, about their test results. Table VII reports whether there were concerns or not. These data suggest that concern about discussing test results with children and other relatives was limited to about one-fifth or less of the population. There was little concern about whom to tell, what to tell, or when to tell children and other relatives.

While our sample is relatively small, we were able to conduct some correlational analyses identifying factors associated with communication of test results. Because our relatives were clustered within 23 kinships, we used SUDAAN statistical analyses for clustered data (Research Triangle Institute, 1998). All analyses used the chi-square statistic for assessing associations.

These analyses suggested that carriers more than noncarriers (47.6% vs. 6.2%; P < 0.001) reported being concerned about when to tell their children their carrier status. Also, carriers more than noncarriers (38.1% vs. 14.1%; P < 0.056) were likely to report concern about what to tell their children about their carrier status.

Additionally, women planning or unsure about a future pregnancy were more likely to report talking with their partner about their carrier status than those not planning a pregnancy (88% vs. 66%; P < 0.024). Women who had higher levels of education were more likely to talk to their partners than women with less education (P < 0.065). Finally, women who had previous non–DNA-based testing were more likely to discuss their carrier status with their sisters than those who had not had previous testing (P < 0.003).