Should genetic testing for BRCA12 be permitted for minors Opinions of BRCA mutation carriers and their adult offspring.код для вставкиСкачать
American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 148C:70 –77 (2008) A R T I C L E Should Genetic Testing for BRCA1/2 Be Permitted for Minors? Opinions of BRCA Mutation Carriers and Their Adult Offspring ANGELA R. BRADBURY,* LINDA PATRICK-MILLER, KIMBERLY PAWLOWSKI, COMFORT N. IBE, SHELLY A. CUMMINGS, OLUFUNMILAYO I. OLOPADE, AND CHRISTOPHER K. DAUGHERTY Although professional guidelines recommend against testing minors for adult-onset genetic conditions, the genetic testing of minors for BRCA1/2 alterations has been debated in the literature. To better understand the opinions of BRCA mutation carriers regarding the genetic testing of minors and the cognitive and affective processes underlying these opinions, we interviewed BRCA mutation carriers and their adult offspring who had learned of their parent’s BRCA mutation. Semi-structured interviews were conducted with 53 parents and 22 offspring. In response to a closed-ended question, 52% (n ¼ 39) of participants were opposed to the testing of minors. Responses to an open-ended question indicate that many participants (24%, n ¼ 18) feel that testing could be permitted for some minor offspring. Psychological risks and the insufficient maturity of minors were frequent concerns of participants opposed to testing minors. The potential to impact health behaviors was frequently cited as a reason to support the genetic testing of minors. These preliminary results suggest that many BRCA mutation carriers and their adult offspring have concerns about, or are opposed to the genetic testing of minors. However, a significant minority in our study would support testing minors. Greater support for testing among offspring could indicate increasing requests for early genetic diagnosis. Further research is necessary to explore the risks and benefits of providing genetic testing to minors for adult-onset hereditary cancer syndromes in order to inform clinical practice and public policy and to ensure optimal psychosocial and medical outcomes for all members in families at risk for genetically determined disease. ß 2008 Wiley-Liss, Inc. KEY WORDS: BRCA1/2; genetic testing; children; ethics How to cite this article: Bradbury AR, Patrick-Miller L, Pawlowski K, Ibe CN, Cummings SA, Olopade OI, Daugherty CK. 2008. Should genetic testing for BRCA1/2 be permitted for minors? Opinions of BRCA mutation carriers and their adult offspring. Am J Med Genet Part C Semin Med Genet 148C:70–77. INTRODUCTION With scientific advances in the genomic era there has been increasing identification of genetic alterations associated with predispositions to a variety of medical conditions. In many cases, manifestations of the disease do not occur until adulthood, such as in Huntington disease and hereditary breast and ovarian cancer. The availability of predictive genetic testing for these conditions has raised several ethical dilemmas, including the testing of minors for adult-onset diseases. The majority of professional groups have recommended against the genetic testing of minors for adult-onset diseases in Angela R. Bradbury, M.D., is an Associate Member at the Fox Chase Cancer in the Divisions of Population Science and Medical Science and Director of the Margaret Dyson Family Risk Assessment Program. She was formerly faculty at the University of Chicago and the MacLean Center for Clinical Medical Ethics. Her research interests focus on ethical dilemmas in cancer risk assessment and predictive genetic testing for hereditary cancer. Linda Patrick-Miller, Ph.D., is Director of the Division of Behavioral Science at the Cancer Institute of New Jersey and Assistant Professor in the Department of Psychiatry at the University of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School. Her research interests focus on the biopsychosocial factors that mediate utilization of and response to cancer risk assessment and genetic testing for hereditary cancers. Kimberly Pawlowski is a research assistant at the University of Chicago and a doctoral student in Psychology at Illinois Institute of Technology. Comfort N. Ibe is a research assistant and medical student at the University of Chicago. Shelly A. Cummings, M.S., is a genetic counselor and Assistant Director of the University of Chicago Cancer Risk Clinic. Olufunmilayo I. Olopade, M.D., is a Professor of Medicine in the Section of Hematology/Oncology and is the Director of the Center for Clinical Cancer Genetics and the Cancer Risk Clinic at the University of Chicago. Christopher K. Daugherty, M.D., is an Associate Professor of Medicine in the Section of Hematology/Oncology and Chairman of the University of Chicago Biological Sciences Division’s Institutional Review Board. His research has focused on ethical issues in cancer care and clinical research ethics. Grant sponsor: Greenwall Foundation, Program in Bioethics; Grant sponsor: American Society of Clinical Oncology, Young Investigator Award; Grant sponsor: American Cancer Society; Grant number: MRSG-07-014-01-CPPB. *Correspondence to: Angela R. Bradbury, M.D., Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111. E-mail: email@example.com DOI 10.1002/ajmg.c.30163 ß 2008 Wiley-Liss, Inc. ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c the absence of medical benefit [Clarke, 1994; IOM, 1994; ASHG/ACMG, 1995; AAP, 2001; ASCO, 2003]. Unlike individuals who have a genetic alteration associated with Huntington disease, carriers of a BRCA1/2 alteration will not necessarily develop cancer. They do have a significantly increased risk for breast cancer (up to 85% lifetime risk) and ovarian cancer (up to 44% lifetime risk) [Ford et al., 1998; Antoniou et al., 2003]. Additionally, effective risk reduction options, such as prophylactic surgeries, heightened surveillance and/or chemoprevention are available to BRCA1/2 mutation carriers. These risk reduction options are generally not recommended until the age of 25 [Burke et al., 1997; Daly et al., 2004]. Thus, it has been argued that there is no medical benefit to testing minors for BRCA1/2 alterations [Clarke, 1994; ASHG/ACMG, 1995; Kodish, 1999]. Despite professional guidelines recommending against testing minors, there is still debate in the literature including both ethical and clinical arguments for, and against, the testing of minors for BRCA mutations and other adult-onset genetic disorders [Cohen, 1998]. Proponents of testing minors have argued that there is harm in uncertainty and withholding information [Cohen, 1998; Rhodes, 2006], and the potential for later misdiagnosis. As well, proponents have argued that there is value in permitting testing in adolescence, including the fostering autonomous decision making abilities [Wertz et al., 1994; Michie, 1996; Elger and Despite professional guidelines recommending against testing minors, there is still debate in the literature including both ethical and clinical arguments for, and against, the testing of minors for BRCA mutations and other adult-onset genetic disorders. Harding, 2000]. Additionally, many argue that parents and their children are more likely than health care professionals to most appropriately assess the risks and benefits of testing an individual child [Sharpe, 1993b; Cohen, 1998; Robertson and Savulescu, 2001]. Opponents of testing minors argue that the development of mature decision-making is variable during adolescence [Richards, 2006] and letting parents make testing decisions for their minor children violates the future autonomy of offspring [Bloch and Hayden, 1990; Clarke, 1994]. Opponents have also cited potential adverse psychological consequences to early testing, including increased disease-related distress and anxiety, distortion of family relationships [Wertz et al., 1994], interference in normal development of self-concept [Wertz et al., 1994], and feelings of unworthiness [Bloch and Hayden, 1990; Sharpe, 1993a; Quaid, 1994; Wertz et al., 1994]. Despite this debate, empirical data to support either argument are lacking, especially in the setting of families affected by BRCA mutations. Initial studies involving the general public [Wertz and Reilly, 1997], health care providers [Clarke, 1994], mothers of pediatric oncology patients [Patenaude et al., 1996] and unaffected first-degree relatives of breast and ovarian cancer patients [Benkendorf et al., 1997] suggested high levels of interest in the genetic testing of minors for cancer susceptibility genes, even in the absence of medical benefit. Subsequent studies specifically involving parents and offspring from hereditary cancer families have suggested lower levels of interest and a concern for potential negative psychological and social outcomes with clinical or research predictive genetic testing [Geller et al., 2000; Hamann et al., 2000; Bernhardt et al., 2003]. As suggested by Hamman et al., the experiences and opinions of individuals who have undergone BRCA testing can be particularly informative in considering this debate. Not only is the controversy directly relevant to them, they are the most immediate potential consumers of such testing and have the most 71 relevant understanding of what it means to live with a predisposition diagnosis [Juengst, 1995; Hamann et al., 2000]. Hammann et al. evaluated the opinions of individuals from a single BRCA1 kindred who participated in research testing and reported that the majority (75%) of participants were opposed to the testing of minors. Factors statistically associated with support of testing minors included being male, having positive perceptions of genetic testing and not having a mother affected with breast cancer [Hamann et al., 2000]. Why individuals supported or opposed testing were not explored in this prior study and, to our knowledge, have not been described in the literature. To better understand the opinions of BRCA mutation carriers regarding the genetic testing of minors and the cognitive and affective processes underlying these opinions, we interviewed BRCA mutation carriers who underwent clinical genetic testing and had children under 25 years old at the time they received their test results. Additionally, we interviewed these individuals’ adult offspring who had learned of their parent’s BRCA mutation and had thus become candidates for genetic testing themselves. The goal of this study was to generate hypotheses to guide further research regarding the genetic testing of minors. MATERIALS AND METHODS Study Population and Recruitment Patients were recruited through the University of Chicago Cancer Risk Clinic. Parent participants included BRCA1/2 mutation carriers who participated in a study evaluating parent communication of genetic test results to offspring and opinions regarding the genetic testing of minors [Bradbury et al., 2007]. Parent subjects were contacted by a research assistant and provided verbal consent by telephone. The offspring subjects were recruited through parent participants. After obtaining Institutional Review Board (IRB) approval, parents who reported having revealed their BRCA mutation 72 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c status to their offspring were re-contacted. A research assistant described the goals and procedures of the offspring study, and invited parents to share this information with their eligible adult offspring. Parents subsequently provided verbal consent and contact information for the research assistant to contact the offspring. Offspring were contacted directly and the research assistant obtained verbal informed consent for the offspring telephone interview study. As previously described, 53 (73% of eligible parents) participated in the survey [Bradbury et al., 2007]. Among the parents who completed the interview, there were 44 adult offspring who reportedly learned of their parent’s BRCA mutation prior to the age of 25 years old. Six parents refused to introduce the study to their offspring and four could not be reached despite repeated attempts, excluding 14 offspring. Of the remaining 30 eligible adult offspring, three refused to participate after their parent introduced the study. Five offspring agreed to contact, but did not complete the survey. The remaining 22 offspring who completed the survey represent 50% of eligible offspring in the cohort with a participation rate of 73% among offspring who learned of the study from a parent. Data Collection and Analysis Semi-structured interviews were developed to elicit personal opinions. There was no attempt to educate participants regarding the topic of interest during interviews and open-ended questions allowed for prompts and exploration of parent and offspring responses. IRB approval was obtained. Relative to the federal regulations and IRB review involving research on genetic testing for heritable disorders, a waiver of consent was obtained allowing for the collection of specific information about participant’s family members (including minor children). Parent and offspring participants were contacted by telephone and verbal consent was obtained. Parent interviews were conducted by two trained research assistants over a 12-month time period (February 2004–February 2005). Interviews lasted approximately 20–30 min. Offspring interviews were conducted by a research assistant over a 6-month time period (September 2006–March 2007) and lasted 15–40 min. Participant responses were recorded and entered into a database for further coding and analysis using STATA (version 9.0). A thematic analysis of the responses was completed using the method of constant comparison [Strauss and Corbin, 1990]. Investigators intensively reviewed descriptive responses to openended questions and coding schemas were developed through open coding. Two investigators (AB, LPM) independently assigned codes to all descriptive responses. The inter-coder reliability for responses to the open-ended question was 98%. Agreement was then established for all responses. Response proportions to individual structured questions and coded responses are utilized to summarize results and representative individual responses have been selected to characterize the data. ARTICLE RESULTS Demographics The study sample consists of 75 adults including 53 BRCA1/2 mutation carriers and 22 of their adult offspring. Participant demographic characteristics are described in Table I. The majority of parent participants were mothers, although the offspring sample consisted of both sons and daughters. Overall, 21% of participants were male and the majority of participants were white and with at least some college education. All parents had received genetic counseling and testing. All offspring were eligible for genetic testing and seven had undergone site-specific genetic testing, with three testing positive for the familial mutation. Opinions Regarding the Genetic Testing of Minors All subjects were asked if they feel that children under the age of 18 years old TABLE I. Participant Characteristics Age in years Median (range) Gender Women Men Race White Black Hispanic Education Graduate College Some collegea High school Marital status Married Never married Divorced/widowed History of cancer Yes History of genetic testing Yes Parents (n ¼ 53) no. (%) Offspring (n ¼ 22) no. (%) Total (n ¼ 75) no. (%) 45 (28–66) 26 (18–33) 43 (18–66) 47 (89) 6 (11) 12 (55) 10 (45) 59 (79) 16 (21) 50 (94) 1 (2) 2 (4) 20 (91) 1 (5) 1 (5) 70 (93) 2 (3) 3 (4) 16 (30) 21 (40) 7 (13) 9 (17) 5 (23) 7 (32) 8 (36) 2 (9) 47 (89) 0 (0) 6 (11) 9 (41) 13 (59) 0 (0) 56 (75) 13 (17) 6 (8) 28 (53) 0 (0) 28 (37) 53 (100) 7 (32) 60 (80) 21 28 15 11 (28) (37) (20) (17) ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c should be given the opportunity to have genetic testing for BRCA1/2. In response to the single closed-item question regarding testing minors, approximately half (52%) of all participants were opposed to the genetic testing of minors. While the numbers are small and this study remains qualitative and descriptive, it is interesting to note that responses differed both by generation and gender. A majority of mothers (32 of 47) opposed the genetic testing of minors, and a majority of fathers (4 of 6), sons (8 of 10) and daughters (7 of 12) supported the genetic testing of minors. Slightly less than half (47%) of participants with at least some college education and a majority of participants with formal education limited to high school (82%) opposed the genetic testing of minors. When offspring opinions were compared to parents’ opinions to the single-response item, the majority of offspring (61%) reported a different opinion than their parent. Participants were asked to explain why they supported or opposed the genetic testing of minors for BRCA1/2 in an open-ended question. Forty-one of 75 subjects provided descriptive responses opposing the genetic testing of minors, while 18 participants provided descriptive responses supporting the genetic testing of minors in specific circumstances (Table II). As in their responses to the closed questions, the majority of mothers provided open-ended responses consistent with opposition to the testing of minors. Many daughters provided descriptive responses consistent with opposition to the testing of minors, although some provided responses supporting conditional testing of minors in specific situations (Table II). Among the small number of fathers and sons interviewed, many provided open-ended responses expressing either conditional or unconditional support for the testing of minors (Table II). Reasons for Opposing the Genetic Testing of Minors The most common reasons given for opposing the genetic testing of minors were the lack of a medical indication The most common reasons given for opposing the genetic testing of minors were the lack of a medical indication for testing, insufficient maturity of minors and concerns that testing could cause anxiety or fear among offspring. for testing, insufficient maturity of minors and concerns that testing could cause anxiety or fear among offspring (Table II). Among mothers, the most TABLE II. Reasons for Supporting or Opposing Genetic Testing of Minors* Coded response Opposed to genetic testing of minors There is no medical indication It could cause anxiety or fear Minors are not mature enough for the information It could affect decisions regarding childbearing It should be delayed so the offspring can decide In support of genetic testing of minors (n ¼ 22) Information can foster healthy behavior Offspring have a right to testing To inform childbearing Age does not matter No harm to testing To eliminate uncertainty Under some circumstances genetic testing of minors could be considered If the offspring is exceptionally mature If parent/offspring perceive a medical indication If the parent desires testing If the offspring desires testing If the offspring is female If the doctor recommends testing 73 Total no. (%) respondents Mothers no. (n ¼ 47) Fathers no. Daughters no. (n ¼ 6) (n ¼ 12) 41 (55) 19 (46) 19 (46) 18 (46) 2 (5) 1 (3) 22 (29) 11 (50) 5 (23) 3 (14) 2 (9) 2 (9) 1 (5) 18 (24) 31 (66) 13 17 14 2 0 9 (19) 3 2 2 1 1 1 8 (17) 1 (17) 1 0 0 0 0 2 (33) 1 0 0 0 1 0 2 (33) 6 (50) 3 1 3 0 1 4 (33) 1 2 0 1 0 0 3 (25) 3 (30) 2 1 1 0 0 7 (70) 6 1 1 0 0 0 5 (50) 7 (39) 6 (33) 6 (33) 2 (11) 2 (11) 1 (6) 5 4 0 0 0 0 1 1 1 0 1 0 1 1 2 1 0 0 0 0 3 1 1 1 *Participants could provide more than one reason and one participant chose not to respond to the question. Sons no. (n ¼ 10) 74 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c frequently reported concerns were that minors were not mature enough for the information and that it could cause anxiety or fear. From seeing my children, the maturity level is not there [under the age of 18 years old]. It would be too traumatic (43-year-old mother). Eighteen is the right age, before then the risk of excess worry is greater than the benefit from the knowledge (38-year-old mother). It is not necessary, in the middle of growing up. They don’t need to think about it (48-year-old mother). Among all subjects, another frequently reported reason for not supporting the testing of minors was the lack of a medical indication. The impact is later in life, it wouldn’t benefit them. There is no current surveillance before 18 (48year-old father). You can’t do anything at that age. I don’t really see how the information could be helpful at this age (28-year-old son). It is not really necessary to know that young . . .because you can’t act on the information (25-year-old daughter). Reasons for Supporting the Genetic Testing of Minors Among subjects providing descriptive responses in support of testing minors, the potential for genetic testing to foster healthy behavior was the most common reason cited in support of testing minors. Some indicated that testing could encourage offspring to engage in healthy behaviors, while others indicated that this information could assist parents in encouraging offspring’s healthy behaviors. If there is no physical health risk, give them knowledge early on. It is better to know at an early age because it could change early health habits (20-year-old son). The earlier the better, since you have the gene when you’re born you might as well find out. It can give a better chance of preventative care (47-year-old father). Other common reasons provided for supporting the testing of minors included the offspring’s right to test, that age should not be the deciding factor and that the information could inform childbearing. We are all born with a particular genetic makeup that’s not any different before eighteen (44-yearold mother). It should be their choice. We should leave it open to people (26year-old son). Yes, because it might affect thinking about family planning (58-year-old mother). Interestingly, the potential impact on offspring decisions regarding childbearing was also a reason given to not allow genetic testing of minors. I don’t think a woman should get tested until she has finished bearing children (50-year-old mother). Reasons for Supporting the Genetic Testing of Minors in Some Circumstances As described above, the responses to the open-ended question suggest that some participants (24%) felt that genetic testing of minors could be considered in certain circumstances. The most common indications provided were if minors had adequate maturity, if either parent or offspring perceived a medical benefit and if the parent(s) desired testing. Some children could handle the results (52-year-old mother). If the family history indicates early preventative measures would help (47-year-old mother). Interestingly, many offspring indicated that testing could be allowed if a parent desired testing for their minor child. ARTICLE It’s up to the guardian if they want to do it (24-year-old daughter). The information has little relevance before the age of 18, but I would want to do research for my own children, and maybe I would want them tested prior to the age of 18 (26-year-old male). On the other hand, one daughter identified the conflict between parent and offspring autonomy, highlighting the potential loss of offspring autonomy in letting parents make the decision for their children. That would mean it’s the parent’s decision and it should be the child’s decision (18-year-old daughter). Parent Opinions Regarding Testing Their Own Children Parents were asked if they would have been interested in testing their own children before the age of 18. Among the 18 parents who supported genetic testing of minors, 11 (61%) indicated that they would be interested in testing their own child. Alternatively, among parents that did not support testing minors, only 1 of 33 indicated that they would have been interested in testing their own child, although five reported that they were unsure. DISCUSSION In this study, we have further described the opinions of individuals from BRCA1/2 families regarding the genetic testing of minors for a familial mutation. In response to two closed questions 44% of participants supported the genetic testing of minors for BRCA1/2. However, only 25% indicated that they would have been interested in testing a minor child of their own. As in other studies that have incorporated open-ended questions to facilitate dialogue and elicit patient opinions and experiences, participant responses to our open-ended question seemed to elicit more thoughtful consideration of the risks and benefits of testing minors [Geller et al., 2000; Bernhardt et al., 2003]. These responses ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c suggest that fewer participants unconditionally support testing. However, 24% described specific scenarios in which they would support testing of minors, including cases of mature minors and parent or offspring perceptions of benefit. The descriptive responses suggest that further research of the potential psychological risks of testing minors, the assessment of adolescent maturity and the impact of early genetic testing on health behaviors could be relevant to potential consumers of genetic testing for BRCA mutations, their health care providers and policy makers. In this study, we found a somewhat higher proportion of participants supporting the testing of minors than previously reported among a single BRCA1 kindred where participants were presented with a similar closedresponse question [Hamann et al., 2000]. While both studies involved family In this study, we found a somewhat higher proportion of participants supporting the testing of minors than previously reported among a single BRCA1 kindred where participants were presented with a similar closed-response question. members from BRCA kindred, there are differences between the studies that may explain higher rates of support for testing minors in our study. Participants in our study presented for clinical genetic testing and completed interviews after 2004. Thus, they may have had different perceptions and incentives regarding genetic testing than individuals presenting for research testing and queried at the advent of genetic testing for BRCA1/2 mutations. Nonetheless, both studies suggest less support for the testing of minors among individuals in families with a known BRCA mutation compared to prior studies evaluating hypothetical situations in other at-risk populations [Patenaude et al., 1996; Benkendorf et al., 1997]. While recognizing the qualitative nature of our study and the relatively small number of men, similar to Hamann et al. , we found that men in BRCA families appear more likely to support the genetic testing of minors. While recognizing the qualitative nature of our study and the relatively small number of men, similar to Hamann et al., we found that men in BRCA families appear more likely to support the genetic testing of minors. It is worth noting that 8 of 10 sons had not received genetic counseling and, thus, might have developed their opinions on the basis of relatively limited or potentially biased information. It is also possible, however, that men and women may perceive genetic information or genetic risk differently. In fact, other studies have reported a greater interest in genetic testing for cancer and other hereditary conditions among men than women [Andrykowski et al., 1997; Sanderson et al., 2004; Barnoy, 2007]. It has been suggested that men have lower levels of distress associated with BRCA testing, perceive less personal responsibility for transmitting a genetic condition than women [Lodder et al., 2001] and process information differently [Barnoy, 2007]. Thus, men may develop different emotional and cognitive representations of genetically determined disease and genetic testing, and may employ those representations differently in developing their opinions regarding the potential benefits and harms of undergoing testing for genetic disease. Men and women may also assume different cultural roles and responsibilities specifically surrounding genetic illness in families [Richards, 75 1996; d’Agincourt-Canning, 2001; Koehly et al., 2003; Gaff et al., 2005]. Given that women are recognized as carrying the responsibility for safeguarding the welfare of their children [d’Agincourt-Canning, 2001], they may develop different perceptions of the risks and benefits of testing offspring. Similar to other studies evaluating parental opinions regarding enrolling offspring in genetic susceptibility research [Geller et al., 2000; Bernhardt et al., 2003], mothers opposed to testing minors in our study most frequently described concerns about the potential negative consequences of testing minors. It has been argued that men and women may both feel a strong imperative to care for their offspring but that the manner in which they perceive fulfilling this imperative may differ [Hallowell et al., 2005]. Thus, providing offspring access to testing may be a means for men to fulfill their perceived parental responsibility regarding their genetic risk. It is also possible that any of the reported gender differences, if real, are unique to BRCA families, given the inherent gender differences in the risks of developing cancer, the procedures used to reduce cancer risk, and the cancers experienced. Given our findings and the previous work of others, we strongly believe that further investigation of gender differences in hereditary syndromes in which expression is similar across gender could prove valuable in informing genetic counseling procedures for adults and children of both genders. Differences of opinion between parents and offspring were also prevalent among participants in our studies. Parents and offspring likely had different information and experiences as they developed their perceptions of genetic disease. Understandably, in this sample, fewer offspring than parents had participated in formal genetic counseling. Of note, a greater proportion of offspring reported higher levels of formal education and this could have influenced opinions about genetic testing. It is possible that younger participants may have had more positive representations of genetic information than their parents 76 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c who presumably had undergone formal education prior to the ‘‘genetic era.’’ Additionally, offspring’s lack of personal illness experience or their developmental level at the time of exposure to their parent’s cancer experience may have led to differences in perceptions of the potential positive and negative consequences of genetic testing for adultonset disease. Thus, any observed differences among parents’ and offsprings’, and males’ and females’ perceptions of genetically determined disease, genetic testing and consequently, opinions regarding the genetic testing of minors are likely the product of complex interrelationships among differences in biopsychosocial factors both external and internal to the individuals. Developing a further understanding of the factors that Developing a further understanding of the factors that mediate any gender and generational differences in families with a genetic predisposition to illness could inform genetic counseling methods and policies for subsequent generations, as genetics becomes a more integral component of health care. mediate any gender and generational differences in families with a genetic predisposition to illness could inform genetic counseling methods and policies for subsequent generations, as genetics becomes a more integral component of health care. While the data are limited, both our study and at least one other suggest a need for continued consideration of alternative policies regarding the genetic testing of minors for BRCA1/2. Given that some individuals achieve social, emotional and intellectual maturity well in advance of their peers, it may be permissible to allow genetic testing of minors on a case-by-case basis. In fact, a study of health care professionals providing genetic services indicated that some health care professions do choose to provide genetic testing to minors for adult-onset disorders for non-medical reasons in specific cases [Duncan et al., 2005]. Thus, providing genetic testing of minors on a case-by-case basis appears to be occurring. As well, for better or for worse, such testing is likely to be supported, and increasingly requested by some consumers. There have been criticisms against the current guidelines and use of age-based criterion [Binedell et al., 1996] as well as criticisms against the use of autonomy and rights based frameworks [Grochowski and Bach, 1994; Binedell et al., 1996; Hallowell et al., 2003]. Alternative frameworks, such as developmental decision-making and family systems theories, might be employed to develop models to study and evaluate the cognitive, emotional and social maturity of BRCA mutation carriers’ offspring in the context of decision-making for predictive genetic testing of minors [Binedell et al., 1996; McCabe, 1996; McConkie-Rosell and Spiridigliozzi, 2004]. In considering alternative policies and future investigations for the genetic testing of minors, the results from our study suggest several additional areas for continued research that could impact the opinions of potential consumers and inform the development of future policies and protocols. Further information regarding how young individuals conceptualize familial risk, genetic testing and risk reduction, and how those perceptions influence their health behaviors could significantly influence the acceptability of testing among potential consumers. If future research demonstrates limited negative psychological impact on offspring, parents in hereditary cancer families may be more supportive of testing minors for adultonset conditions. Alternatively, if longitudinal studies suggest that early testing does not initiate and/or sustain risk reduction behaviors, or that early behavior change does not impact the develop- ARTICLE ment of adult cancer, one would expect less support for early genetic diagnosis. As a descriptive and qualitative study, this research was designed to be hypothesis generating. Additionally, participants in this study were predominately white, female and highly educated. Any associations or patterns suggested by our work will need to be further evaluated in larger studies of broader populations that include additional assessments of constructs such as participant perceptions of genetically determined disease, genetic testing and their consequences, and the factors and experiences that shape the development of these perceptions. In conclusion, our results suggest that opinions within and among BRCA families regarding the appropriateness of the genetic testing of minors varies, with almost half of our interviewed subjects potentially supporting the genetic testing of minors. Despite this, only a minority of participants would consider testing their own child. If there is indeed greater support for testing among offspring in BRCA1/2 families, there could be increasing requests for early genetic diagnosis. 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