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Psychology of Predictive Testing
Transcript of Psychology of Predictive Testing
(impact for future generations) Less than 25 - normal Over 39 repeats - HD 27 or greater repeats associated with meiotic instability Larger size of repeat loosely associated with younger age of onset Thesis Predictive genetic testing for later onset conditions can be beneficial in planning for the future, prevention, and coping, but should be done with a professional counselor in order to fully understand consequences and benefits of testing as well as prevent psychological issues. Disease Facts The Mutations Disease Facts Dementia Testing Outcomes Positive - carrier of known mutation predisposing to cancer Few receive a true negative and many results are indeterminate. In 1999, 70+% of tests were indeterminate. Some can be clarified to true negatives by testing other family members. HNPCC & FAP Colorectal Cancer FAP The Mutation Dementia is an acquired loss of cognitive function in 2+ domains Early-Onset Late-Onset Most common and best-studied form of dementia Chromosome 21: amyloid-B protein precursor (APP) Chromosome 14: presenilin 1 (PSEN1) Chromosome 1: presenilin 2 (PSEN2) Mutations Chromosome 19: Apolipoprotein E gene (APOE) These three mutations don't account for all cases of early-onset Alzheimer's disease These 2 genes (mainly PSEN1) account for 50% of early-onset AD
Almost all PSEN1 are fully penetrant
Age of onset w/PSEN1: late 30s to early 50s
Age of onset w/PSEN2: 52, varies from 40-85 Age at onset w/APP mutation: late 30s to early 60s
Fully penetrant mutation APOE has 3 alleles 35-65% AD patients lack APOEe4 allele, and only 12-15% have 2 copies, so it is likely that it accounts for AD in about 50% of cases. Who Gets Tested? No cure Limited interest in testing among families at risk Early-onset AD accounts for <1% of all AD Penetrance for APOEe4 is less understood, leading to more uncertainty of whether or not the disease will occur. Patients who referred themselves for testing versus those in an Alzheimer's registry were more likely to go through with testing.
(64% vs 24%) Individuals with a college education and those under 60 were more likely to test Reasons for Testing hopes of prevention Second leading cause of cancer death in US, with an estimated 56,730 deaths in 2004. Types of CRC Sporadic CRC: no family history (65-85%) Familial CRC: 1+ relatives with CRC but no high-risk pattern (10-20%) Both of these are preventable if screening is properly employed and arise in late adulthood Hereditary CRC: genetic susceptibility is primary factor (5%) Likely caused by low-penetrant genetic factors, environmental and behavior factors Alzheimer's disease represents 50-90% of all dementias Overall prevalence of dementia is 5-10% in older adults. Prevalence is fairly low in early 60s, but doubles for every 5 year increase in age The prevalence of dementia in 90-95 year-olds is 25-40% Best established risk factors for dementia:
female gender Genetics Psychology Who Gets Tested? Only 10-25% of at-risk individuals have taken a predictive test Patients who get tested are likely a self-selected group with good psychological resources More females get tested than males - women as genetic housekeepers, involvement in reproduction, willingness to face health issues Why only 10-25%? Complicatons: infection, aspiration, heart failure No cure. "Participants choosing not to be tested is not denial but a positive way to preserve both hope and their identities as people with a future." - Etchegary Voluntary avoidance of certainty See future as something determined by luck or fate, not genetics Nearly 100% penetrance Before predictive testing for Huntington's was available, surveys said 75-79% would get tested BUT... More likely to overestimate risk Anticipated problems coping with information Motivations for Testing Huntington's Disease "Until recently, medicine recognized two types of people: the well and the unwell. Genetic testing of asymptomatic people at risk for inherited disease has created a third category: the apparently well, those who are not yet ill but know they will be."
-Miller More expectations of unfavorable emotional reactions and hopelessness Planning motivation: make decisions involving family planning, informing children Uncertainty motivation: expect test to solve problems and uncertainties, but don't know what they will do with their results Preserves hope "as a means of keeping open the possibilities of a disease-free future" for themselves and their children Young adults: make life decisions Older parents: find out risk to children Newly at-risk individuals: reassess future plans Affected: confirmation of disease Lack of effective treatment or cure Insurance discrimination Perceived ability to make decisions without testing Cancer Genetic mutations, increased age, previous history of breast cancer, family history, and reproductive and menstrual history are risk factors HBOC = Hereditary breast and ovarian cancer Breast cancer is the most common nonskin cancer and the second leading cause of cancer-related death in women. 2005 statistics - Estimated 269,740 individuals diagnosed with breast cancer each year Characterized partly by alterations in BRCA1/2 Indicated in families with young breast cancer diagnoses, male breast cancer, ovarian cancer, or multiple family members who have been diagnosed with breast or ovarian cancer Inherited forms of breast cancer account for 5-10% of all cases. BRCA1 - chromosome 17, discovered in 1990s BRCA2 - chromosome 13, discovered soon after Autosomal dominant Autosomal dominant Function in tumor suppression and DNA repair Women with BRCA1/2 mutation are 3-6x more likely to develop breast cancer and 9-35x more likely to develop ovarian cancer Other Mutations BRCA1/2 don't account for all hereditary breast cancer Li-Fraumeni syndrome: mutations of 953 gene on chromosome 17p Cowden's syndrome: mutation in PTEN (protein tyrosine phosphatase) on chromosome 10q23 Other hereditary breast cancers likely have multiple genes involved Incomplete penetrance (27-55% or 80% for BRCA1/2)
Gene penetrance + age-specific penetrance Options for Carriers Screening
mammography as young as 25-35 years or 10 years below age of youngest cancer diagnosis in family MRI for routine screening
transvaginal ultrasound every 6 months
CA-125 blood test Indeterminate/Inconclusive - surveillance based on family history Chemoprevention: block/prevent processes leading to tumor development
Hormone-based interventions (Tamoxifin)
Shown to have risk reduction in women who took for 5 years - 50% Motivations for Testing Decision based on short term goals (reduce uncertainty) and potential long-term psychological consequences (surgery if positive) Women overestimate risk for hereditary breast cancer and misunderstand genetic testing limitations. Difference between being at risk due to age or family patterns versus due to genetic mutation is hard to process. Who Gets Tested? Women with higher education and use the internet have more knowledge of breast cancer genetics and awareness/interest of testing Risk Perception Before genetic counseling, women inaccurately estimate their risk. Most with some family history of breast cancer overestimate. High-risk individuals overestimate risk more than lower-risk individuals. White women with a family history of breast cancer display better overall health behaviors than the general population High levels of breast cancer worry and distress are linked with an overestimation of risk Monitors = higher perceived risk for ovarian cancer - led to thoughts of cancer threat and distress. African Americans generally have less knowledge about breast/ovarian cancer genetics than whites. Around 80% of people with family histories of breast/ovarian cancer report interest in testing BUT... Only 50% of high risk women actually get tested Why Not? Uncertainty of result Anticipated distress Concerns about impact of testing on family stress Health insurance Limited management options Greater levels of risk knowledge and inflated perception of risk is associated with more interest in testing Decision is more based on perceptions of risk than by understanding of genetic testing Those with greater perceived benefits of testing, such as information for family, learning about their risk, and help deciding about options are more interested in testing Greater value on family/need to know for children leads to increased interest People with higher family cohesion and optimism are more likely to get tested Anticipated difficulty disclosing results to family Anticipation of stigmatization Guilt about relatives who are carriers Fear of discrimination Test Expectations Anticipate depression and anxiety if positive or guilt and worry if negative High monitors anticipate that genetic testing will have a negative impact, experience higher levels of anxiety waiting for results, and more mood disturbance after counseling Those who get recruited by a relative are more likely to get tested 76% of women diagnosed with breast cancer opt for genetic testing after diagnosis Ashkenazi Jewish women are more likely, African Americans less likely Counseling Considered computer-based, video-based education about genetics rather than counseling "Use of computer-based educational aids leads to significant increases in genetics knowledge. . . in comparison, individualized counseling approaches are perceived as most useful in addressing personal concerns and minimizing anxiety and fears."
- Miller For those that are unaffected, counseling decreases perceived likelihood of being a carrier, but increases perceptions of risk. Worry and anxiety generally decrease after counseling but mainly for those at lower risk and those whose perceived risk accuracy has improved. Carriers Stress greater among those who receive a positive result Coping Long-term coping: monitors or blunters. Race and Genetic Testing Decline in short-term anxiety, but distress about risk, depression, and concern are greater for carriers. Those with the most sustained distress are unaffected or recently diagnosed carriers. Affected carriers experience more anger and distress than they anticipated. Distress is greatest among those tested first in their family, or those whose siblings are non-carriers. Greater anxiety symptoms and worry up to 2 years after result Generally, a positive result leads to more screening procedures Affected women show no change in distress or perceived risk after results
Unaffected women show decreased distress if they are non-carriers Who Gets Surgery? After counseling, more than half of carriers choose prophylactic surgery. In another study - 27% carriers, 5% uninformative, 2% non-carriers chose prophylactic oophorectomy Younger, highly educated individuals with a larger family history and high distress often choose prophylactic mastectomy.
Those who are older or have breast cancer are more likely to get a prophylactic oophorectomy. Physical Effects of Surgery Presurgery genetic testing for those who are affected can influence decision of which treatment to choose. Psychological Effects of Surgery Decreases in psychological well-being, but no sexual discomfort or degree of sexual pleasure Telling the Family Most women have intentions to share information with at least one relative. Men are often excluded from information. Family rifts can prevent information from being shared with all relatives. Non-Carriers Can experience difficulty adjusting to good news and disclosing it to relatives Confer a lifetime risk of 35-85% for breast cancer and 16-60% for ovarian cancer BRCA mutations are seen in less than 0.5% of the population and account for around 5% of breast cancer cases Stable or somewhat increased distress after results Decrease in distress after test results Means of coping with family cancer history Study by Watson - cancer-related worry and intrusive thoughts increased one month after results Less likely to report positive experiences (feeling happy about result) a month after results Cancer-related worry decrease Unaffected carriers face future health threat and decision making Indeterminate or inconclusive leads to ambiguity and more distress Distress for several months. General distress (depressive symptoms, negative mood) increased and positive mood decreased. After 1 year moods, cancer distress and depressive symptoms neared baseline. Direct-to-Consumer Face-to-face with genetic counselor leads to greater risk comprehension, emotional support and guidance Control Battle for control - over uncertainty, disease Witnessing Cancer Causes psychological scarring, living in fear, or buffer of previous cancer Genetic testing is a way of problem-focused coping - trying to gain control by preparing for future. Most getting genetic testing have family history of HBOC, so they have seen relatives or experienced self-suffering Leads to a heightened fear of cancer and anxiety. "You're looking over your shoulder all the time. There's no way out of cancer, once you've hat it. . . it's there with you whether you like it or not, whether they tell you it's gone or not, you're looking over your shoulder all your life . . ."
-Buckmaster Face-to-face is more effective because it helps to assess how an individual may react. Counseling leads to positive experiences - aimed at targeting factors that have an impact on distress. Families compare members who had cancer in lifestyle, age at diagnosis, personality, and physical characteristics. They emphasize similarities between them and members, increasing or decreasing their risk perception 27% African American women at risk for breast/ovarian cancer discussed testing with spouses versus 66% of Caucasian women Partners Communication and social support are key in adjustment, because patient's response to cancer can be affected by the level of support they experience. A lack of communication interferes with the adjustment process for the patient and partner and may lead to an end of the relationship. The more a partner is satisfied with communication about the illness, the less they fear recurrence.
When both partners take an active part in making decisions, there is less stress on both of them. A lack of family support leads to difficulty in making decisions about prophylactic surgery. Partners who attended genetic counseling often knew more about genetics than those who didn't, and up to 1/3 of partners thought it would be beneficial to know more about BRCA1/2 84% of partners in study thought their wives had a mutation, and believed that there was a greater likelihood that their wives had a mutation. 71% of partners thought there was a moderate chance their wife's cancer would recur. This concern is major and may persist for a long time Partners were more wary that testing would negatively affect health insurance than patients. Patients are responsible for communicating results to family members, which can be stressful. Distress & Anxiety Trait anxiety led to higher perception of stress when dealing with decisions and a lower perception of confidence in managing concerns after testing Highly anxious people are more likely to encode situations in a threatening way "We aren't really that close . . . and she basically sent out an e-mail to the family . . . and she said, "The good news is that I am done with chemo and everything is fine, . . . the bad news is I got my genetic test back and I have this mutation, and you probably have it too, so go get tested." . . . It came out of the blue." - Crotser Each first-degree relative of a carrier has a 50% chance of inheriting that mutation Communicating results to family members causes distress in testing patients Those who get tested see it as their duty to communicate results, but also see it as a burden. Protect from distress, but make aware of potential threat, provide risk information, encourage testing, and receive some emotional support Harder when receivers don't want information or have trouble understanding it.
Often difficult for informers to explain the results themselves. 75% would like resources or to speak with others who have lived through it. Those who aren't as close geographically or emotionally may tell family over the phone, in emails, or in letters. There is no interaction and it is impersonal, and surprising, but receivers are grateful for the information. Family Reactions Shock, worry, anger, numbness, isolation, relief Many pursued own genetic testing, but were
shocked at results even if they had prepared for worst Took a lot of time to consider genetic testing - months/years Seek support from friends, families, church. Hard to find others with experience of BRCA
- FORCE (http://www.facingourrisk.org/messageboard/index.php) Seek direction from healthcare professionals and those with experience of mutation. Shift of purpose and meaning in life after risk One study - no change in distress for most, but for those who have elevated distress it declines over time as they adapt. Self-Concept Any new information about self can harm self-concept. Offspring have a 50% chance of inheriting the mutation Prophylactic oophorectomy is associated with a reduction of anxiety and uncertainty. Loss of breasts or ovaries and reproductive function - reconstruction Those with positive self-concept may be better at coping with negative life events. Those with negative self-concept may have more difficulty coping with testing and surveillance. Prophylactic surgery has greater impacts to self-concept in younger women than older women Living with ambiguity of not knowing if you will get cancer or not can be psychologically distressing Ex) Woman with strong family history of early breast cancer and a sister who tested positive for BRCA1, considered predictive testing at 20, then 24, but deferred after pretesting counseling. Got testing when she and husband were thinking of starting a family. Deciding to start a family Nearing age of cancer diagnosis in family member Another family member gets a positive test result "In some families in which breast and ovarian cancer has occurred with higher than expected frequency, all the female blood relatives in the family may have considered themselves at high, if not certain, risk of developing these cancers. Genetic testing, if undertaken, may now divide the family into those truly at increased risk and those without the BRCA1/2 mutation who are only at the population risk of approximately 10%."
- Miller Uptake of surgery in US is 0-15%, in Europe 50% Interference with breastfeeding Higher level of distress Regret - more common if main reason for procedure was physician's advice Survivor guilt Hard for non-carriers to tell family members their results and support relatives who are carriers or haven't been tested Male BRCA2 carriers have a breast cancer risk of 6% and BRCA1/2 carriers have a 6-14% increased risk of developing prostate cancer Benefit Finding Mortality threat and life disruption can bring around positive life changes Short-term increase in distress stems from risk of future cancer and decisions that must be made about treatment as well as communication of risk to family Prophylactic surgery Affected carriers use approach-oriented coping strategies to manage testing stress, such as problem-solving and emotional expression. Degree of partner support is predictive of psychological symptoms and satisfaction with relationship
Protective buffering - predicts distress
Positive actions: support of decisions, discussion, comfort sharing concerns.
Negative actions: not supportive of decisions, uncomfortable in discussion of experience, avoiding topic
Participants in a study who felt their partner was supportive in pretest discussions had less distress after results and vice versa. Barriers to telling family:
lack of perceived usefulness
seriousness of message
possibility of rejection
age/illness of relative
don't want them to feel blame
difficulty explaining technical terms Majority in study (63%) by Barsevick intended to tell 1st degree relatives, nearly all (98%) intended to tell some relatives. Problem-focused coping styles: active coping, planning, seeking social support Breast cancer is life-threatening, but prognosis is good with current treatment Primary and Secondary Appraisal Primary: assessment of the degree of threat from the event (genetic test) Lifetime risk of breast cancer is 12% for the general population Risk of ovarian cancer for the general population is 2% If risk is seen as controllable, patients employ problem-focused coping strategies - seek information If risk is seen as uncontrollable - employ emotion-focused or avoidance strategies Women who had breast cancer felt as though they could control it, while those who hadn't had it overestimated its negative consequences. High perceived risk is associated with more psychological distress Where relatives get information from matters - testee or genetic counselor.
Can lead to altered perceived risk Sporadic breast cancer accounts for majority of cases - generally in women over 50 Familial breast cancer accounts for 20% of cases - 2+ cancer cases in extended family Many families at risk have their own mutation Pre-test counseling: describe patient's risk status, explain what it means to have an inherited susceptibility to cancer, inform about testing outcomes, appraise risks, benefits, and limitations, discuss possible treatments, how it can be passed to children, psychological issues. Post-test counseling: help understand results, explanation of result, options and surveillance, how to make use of genetic information Inconclusive - carrier of mutation that has no known significance Indeterminate - not carrier of known mutation, carrier status of other family members is negative or unknown Negative - not carrier of known mutation positively identified in another family member Variant of unknown clinical significance (VUCS) Uninformative Higher uncertainty = higher distress Distress levels for those who received uninformative results were higher than non-carriers and near or slightly lower than carriers Distress declined from pretesting to a month after results and remained stable Difficult to make risk-management decisions Women with VUCS reported higher distress Incontinence Hard to detect in early stage, asymptomatic until later stages Prophylactic oophorectomy - 45-50% risk reduction No hormones - hormone therapy Another study: 48% carriers, 25% uninformative chose mastectomy Low risk women are less inclined to get surgery due to fear of cancer, reproductive plans, desire to keep ovaries/breasts, risks for hormone-related diseases Those who get surgery decide its necessary to reduce cancer worry Seeing a relative with cancer makes women more likely to get surgery Most people satisfied with surgery Prophylactic mastectomy - reduces breast cancer risk by 90-95%
Subcutaneous - 90% tissue removed, nipple preserved
Total - 95% removed
Cancer can STILL develop Opting for surgery is linked with family history, personal history, physician recommendation, and having young children Higher levels of distress or perceived risk increase probability of surgery Feel a loss of sexuality, femininity Sense of relief and lessened distress Self-conscious about appearance, feel less attractive Distress, Depression & Anxiety Some individuals have trouble coping, but overall most participants adapt to information regardless of result No significant difference in psychological stress between those receiving an increased risk versus decreased risk Study - after 3 years - decreased risk had less distress while increased risk had no change Suicide attempts 0.5-12.7% of HD deaths are from suicide (4x general pop.) Elevated baseline depression scores have shown an increased risk of depressive symptoms post-test Decreased risk = improvement in quality of life sustained for 5+ years
Increased risk = initial reduction in anxiety, improvement in well-being for 2 years, return to baseline after 5 Partners Partners pessimistic about future and more depressed by a positive result than carriers Sobel & Cowan - a positive result produces an ambiguous loss - all is well now but loss will happen
Grief about a loss that can't be acknowledged or mourned Dissonance Theory Decruyenaere - distress remains high after testing in 35% of people - asked for test because of uncertainty with no planned actions Carriers Became more hopeless, pessimistic 7-10 years after testing because of approaching age of onset, onset of HD in relatives, and occurrence of subtle symptoms 10-15% of carriers and non-carriers experienced some psychological problems post-test, including a burden, depression, hopelessness about future, concern about children, and survival guilt. Counseling Pre/post-test counseling may be part of why there are not as many problems after results Pre-test distress is a better predictor of post-test distress than the test result is Shana Martin Carriers have more negative feelings about test result and avoid HD-related situations and thoughts Pre-test ego strength is a predictor of post-test distress Test motivation predicts long-term distress - uncertainty reasons leads to more distress before and after test than those who want for specific reasons In carriers and non-carriers, distress decreased over long-term and ego-strength remained high over time Predictive Testing Presymptomatic testing reveals genetic mutations associated with dominantly inherited conditions with complete penetrance
Ex) Huntington's disease Feel more hopeless and tend to be more depressed Non-Carriers Coping 52% non-carriers had efficient coping compared to 18% carriers Need follow-up regardless of result May have a change in identity from living with the idea they had the disease, recover from being at risk. Difficulty with result because of survivor guilt, regret for decisions made due to perceived risk, inability to leave behind risk status, disbelief at result, and reactions of family Symptomatic carriers were as depressed as those who were asymptomatic Those undergoing genetic testing showed a decrease in anxiety and depression in first year after testing Ex) Woman lost mother and several aunts to HD and expected to die from the disease but tested negative.
"The one constant thing in my life has now been taken away." - Gargiulo Getting a negative result can be distressing when life was planned around having disease Emotional numbness, sadness, depression, anxiety, anger Miller - 10% non-carriers still have trouble coping up to a year after results - guilt, disappointment that test didn't resolve life problems, no plans for future Family Illness causes a change in roles in a family Can cause overprotection of person at risk for HD: anticipated loss Preselection Subjective risk assessment - estimate risk to be higher than 50% Some end relationships due to result Can lose membership in families where HD is part of family identity Some want to get rid of pain in family history - disconnect Family disconnect when some choose to get tested or not Communication styles can impact relationships Sense of loss and grief in testing (lose uncertainty) or relief and closure Mourn for children and parents HD support groups seen as daunting for asymptomatic carriers "When dealing with inherited diseases, the family is the patient."
- Miller "As a person who had presymptomatic HD testing said, 'This (the testing) will change everything, not only for you, but for your family forever'"
-Sobel and Cowan Though testing and counseling can't help stop HD, they can help in future coping Individual coping style is a key factor in decision to get tested Perceived Risk Increased contact/less positive experience with HD in relatives affects how threatening it is to be at risk Primary appraisal: assessment of threat Coping Coping strategies: "constantly changing cognitive and behavioral efforts to manage specific external and/or internal demands that are appraised as taxing or exceeding the resources of the person."
-Pakenham Avoidance coping is a reason for not getting tested - protects from distress but can harm.
Passive coping: wishful thinking, self blame, avoidance - lead to poorer adjustment
Problem solving, seeking social support, and emotional coping = better adjustment Social support related to better adjustment during testing process and after result Health locus of control - internal (self-determined) or external (luck, fate, other people). Lower self-efficacy and control appraisals, higher threat, passive avoidant coping Important for partner to accompany proband - helps both get support When family members accompany proband and also get support, it benefits both more than supporting either alone Problem solving style of coping allows proband to get more out of counseling Hypervigilance for symptoms HNPCC (Lynch) The Mutation HNPCC = hereditary nonpolyposis colorectal cancer
Also called Lynch syndrome High risk of colorectal, endometrial, endometrium, biliary tree, stomach, ovaries, renal pelvis Most common form of hereditary colorectal cancer Accounts for 2-7% of all colorectal cancer cases Mutations in MLH1, MSH2 - 90% of HNPCC Familial adenomatous polyposis Inevitable cancer
Surgical intervention is necessary, not optional Coping Defensive pessimism - psychologically prepare for worst-case scenario Autosomal dominant Autosomal dominant High frequency (25-30%) of spontaneous germ line mutations Accounts for 1% of CRC cases 100% penetrance Incomplete penetrance Early onset Often in right side of colon Germline mutations of genes responsible for DNA mismatch repair Short DNA sequences are repeated (and not replicated properly) leading to abnormal MLH1/MSH2 proteins 70+% risk of colorectal cancer before age 70, 40-60% risk of endometrial cancer before 70, 50% risk of second cancer within 15 years of initial diagnosis 3+ cases of CRC in 1st degree relatives with one under age 50 are considered high risk - genetic testing Options Screening
Colonoscopies every 1-2 years starting at 20-25
Endometrial screening 30-35 Surgery
Total abdominal hysterectomy
Oophorectomy 100s-1000s of precancerous colonic polyps
Near certain progression to CRC if surgery is not performed By 15, 50% have adenomas, by 30, 95% Average age of diagnosis of CRC is 34-43 if colon and rectum not removed Mutation in APC tumor suppressor gene Variations Attenuated FAP (aFAP) - fewer polyps Gardner's syndrome - no polyps but CRCs that develop at a young age, plus benign tumors of the skin, connective tissues, and bones Arise from APC mutations Genetic testing identifies an APC mutation in approximately 90% of clinically diagnosed individuals Surgery Colectomy - removal of colon or part of it Major surgery - can leave patient with exterior ostomy applicance to catch fecal waste Psychological Effects of Surgery Surgery recommended for late adolescence - can negatively impact identity formation If surgery happens at a later age, there can be challenges of marriage and family planning Difficult on children - surgery recommendation at a younger age Testing Children FAP is early onset, so children can be tested if they have affected parents Genetic testing generally not offered to children No treatment interventions, but surveillance Development of CRC before 20 are rare, so surgery isn't recommended for children. Without testing, at-risk children would need sigmoidoscopies frequently for screening Children don't exhibit significant distress over the first year after testing Children may be negatively perceived by peers if they have FAP Results Limitations: results may not be clear-cut if no family mutation identified Can't have true negative unless you have a family mutation identified To Get Tested or Not? Some don't get tested because they feel test limitations outweigh benefits Give family members a chance to be proactive about their health and see this offsetting limitations Non-Carriers For non-carriers, their negative result can give them a false sense of security Carriers Variant of unknown significance - don't know if it confers risk = distress Indeterminate or uninformative negative results Variation of unknown significance Chemopreventive agents
cyclooxygenase-2 (COX-2) inhibitors
calcium and folate Concern for family and selves - children, relatives Greater family support and need for social support Family Stress from decisions about communicating results to family Survivor guilt about siblings or other family members Concern for children Decision influenced by physician recommendations, family input, perceived costs/benefits of screening, and closeness to a family member who is affected. Physician input + perceived benefit Closeness to affected siblings increases desire for testing Decision depends upon lifetime values/goals Impact of health-related information depends on how it is interpreted and how personal values are activated in response
why someone might delay surgery (body integrity)
avoid surveillance (produces anxiety) Those who perceive health benefits associated with screening are more likely to get screened Increased level of belief that individual doesn't have control over fate (fatalism) and low expectation of screening usefulness leads to poor rates of screening Lack of knowledge about genetic aspects of CRC have trouble making decisions about screening Perceived risk (up to 50%) and perceived confidence in coping ability Distress Elevated risk perception leads to increased distress about cancer In another study - increased perception of CRC risk, CRC risk compared to others, and increased certainty about developing CRC associated with more anxiety, distress, and depression Negative feelings - not feeling cured by treatment, unhappiness and worry 1 month after result More anxious and afraid of cancer immediately after results, then decreased Less anxious and afraid of cancer than carriers after results No long-term harmful emotional impact after 1 year in Finnish study HNPCC - asymptomatic carriers can have increased distress Higher mood disturbance and lower quality of life before results predicted higher depression, anxiety, distress, and lower quality of life regardless of results Who Gets Tested Utah/Canada phone survey
80% were somewhat interested in testing for hereditary CRC
40-47% very interested
Interest decreased when informed that HCRC only in 1% of population High-risk families - 26-70% interest In one study, 26% of participants had definite intentions for testing
less than half - probably test
46% interested in counseling Earlier study of CRC patients
51% intended to get tested
80+% wanted to know if more screening was needed, if children were at risk, to be reassured, and plan for future Insurance concerns Cost Risk perception can influence screening behaviors and treatment decisions positively MSH6, PMS2 Families have beliefs about ways cancer can be passed on How family communicates is important Predispositional testing reveals gene mutations that are risk factors for disease, where a mutation means increased risk
Ex) hereditary cancers, Alzheimer's disease. Most genetic testing involves reproductive tests, though predictive testing is becoming more frequent BRCA1/2 FAP uptake 80% b/c effective treatment Uptake generally increases when a test is offered in person and can be done immediately versus a letter (by 10%) High uptake valuable for conditions with treatment Getting Tested Interest more related to perceived risk than objective risk Extent of uncertainty, need for certainty, and how much tests are seen as bringing certainty influence decision Reducing uncertainty is a common reason for predictive testing Distress Women more likely to get tested + result: slightly more distressed, but within
decrease in distress as uncertainty decreases
- result: difficulty adjusting
decrease in stress Risk Belief of higher risk leads to expectation of positive results - could explain less distress than those not aware of risk Social support and psychological resources affect coping ability Mood before testing is more indicative of reaction to result than result itself - distress before leads to distress after Genetic Disease Genetic + illness leads to a negative connotation Leads to assumption that genetic illnesses are not preventable/treatable When something is determined by a genetic test, it is seen as less preventable "If people do not consider genetic tests in the same light as tests for biological risk factors of disease they will not be motivated to change their behavior."
- Guyatt Counseling "The reason such programs have not had catastrophic effects is likely to be due to such counseling."
- Guyatt Counseling before and after results Way information is presented affects perception and response
-relative vs absolute risk
- gains vs losses Families Family structure affects how individual responds to information Affects motivation (test to inform family, because of family deaths, no test because no family members at risk, family survived well in past) Reaching out to extended family Family story alteration Misinterpretation of word "mutation" Can lead to stigma, discrimination Usefulness Imperfectness of test results - uncertain Negative isn't always a 'true' negative Strong family history and negative result could mean there is an unknown mutation Useful if there is no treatment/prevention? Usefulness of knowledge? Family Systems Theory Illness affects family, but family affects illness.
Coping and adaptation affect disease course, treatment adherence.
Changing family can change patient. Time Phases of Illness Crisis Create meaning for disorder to feel in control
Grieve loss of previous family identity
Family flexibility, possible loss and uncertainty
Redefine 'normal' and live with disease Chronic Pace to avoid burnout
Relationship imbalances (caregiving)
Juggle family needs
Redefine goals within illness Terminal Acknowledge approaching loss
Family reorganization Penetrance High penetrance - family must get used to idea that disease WILL occur
Higher penetrance - less uncertainty, can prepare more for future
More distress about planning and hopefulness
Lower penetrance - more uncertainty Time of onset Onset earlier in life is harder on family
parenting Flexible family structure/roles Conceptualizing Illness Awareness Phase Potential awareness of some genetic risk because of family history
Could be unaware of risks Crisis Phase I: Pre-testing
Considering of testing
Understanding of genetic knowledge
Deciding to test or not
Considering impact of testing on family
Considering who to tell and who to involve in decision Crisis Phase II: Testing and Post-testing Acknowledge and accept genetic knowledge
Grieve for changes in family identity
Create meaning for disease that helps feel in control
Revisit commitments and goals
Decisions about surveillance and lifestyle options
Type of disorder affects this phase
Gradual onset - time to adjust Periodic and ongoing support is helpful for different periods in cycle of disease Long-Term Adaptation Phase Span between result and disease onset
Short, or extend decades or full life if disease never emerges
Family resilience by finding appreciation of positives from disease
Acknowledge possibility of future loss
Remain current about treatment, risk Transition Phase Times before and after testing
Family members try to fit life plans and dreams into illness challenges
Unfinished business in one phase can inhibit movement to next phase
Adaptation strategies in one phase may not be good for another phase Children If aware something runs in family, testing, caregiving, and loss issues can arise when they consider dating, marriage, and starting a family Informed consent model - guide patients in a nondirective fashion to consider benefits, limitations, drawbacks of testing. Beyond decision to test - risk management, treatment options, impact of decisions psychologically Overwhelming amounts of information that need to be communicated effectively "The decision to learn one's genetic information is not merely a single decision about whether to obtain a genetic test, but rather a series of decisions about how to manage one's genetic risk."
- Miller Must consider risk management options if positive when considering decision Fear of passing mutation on Many people have unclear knowledge about genetics Those with more knowledge of genetic risk and higher education in general are more likely to endorse testing benefits Lack of understanding of numbers - percentiles, proportions More likely to overestimate risk when it was believed that physician minimized risk to reduce their worry Personal schemas about world and illness Encourages to think about worst case scenario - defensive pessimism Distressed individuals recall less from counseling sessions than non-distressed individuals Greater perceived threat to self leads to higher uptake of testing Some don't get tested because they don't think they can handle results Some who don't get tested experience higher levels of distress over time Helps individual figure out why they are getting tested, how they expect to feel, form plan of action Distress increases when individual has closely experienced disease in family High/Low Monitoring High monitors Focus on health threats
Prefer a lot of information
Greater risk perception and distress
Greater vigilance to prevention behavior and management options
More interested in testing Low monitors Minimize and avoid health threats
Lesser risk perception and distress Strong senses of self-efficacy and family connection Adaptability Flexibility and family roles Cohesion and communication
closed communication leads to more distress later on Gender Monitors - look for information
Blunters - distract and avoid, move on Anticipatory loss Perception of risk more correlated with interest in testing than actual risk "Have's" vs "have not's" genetics = fate White women see breast cancer as genetic and environmental, while black women attribute it to personal behaviors More anxiety around symptom development, testing, a diagnosis, or family planning Getting testing is a way to optimize feelings of control Guilt Feel more in control, higher perceived ability to cope than hereditary breast cancer patients - better screening Passive coping is related to distress and worry
Seeking distractions was also a less adequate way of coping Seeing cancer as an uncontrollable disease because of genetics leads to more distress Many underestimate their response to getting a positive result, leading to higher distress for a longer period of time Being first in family to get tested can increase distress, because they are the first to hear results Fear of cancer Relief Without counseling, patients may have a lack of knowledge and preparation for emotions of testing "Most candidates for such a disease don't get tested."
- Grierson "Toxic knowledge" "Why would we prefer to know the worst than to suspect it? Because when we get bad news we weep for a while, and then get busy making the best of it. We raise or consciousness and lower our standards. We find our bootstraps and tug. But we can't come to terms with circumstances whose terms we don't yet know. An uncertain future leaves us stranded in an unhappy present with nothing to do but wait."
- Daniel Gilbert Cons More speculative than definitive Many read SNPs (single nucleotide polymorphisms) - small variations in genome
Not as accurate. May only account for small change in risk. SNPs don't always associate with diseases consistently in studies Risk predictions can vary between companies Equipment is 99.99% accurate. . . BUT that means 3 million errors in a genome with 6 billion base pairs Pros Whole-genome sequencing price could someday drop to under $1000 Protective ignorance for highly penetrant diseases Professionals from many departments play a part Communication through internet, no personal interaction No need to go through health practitioner Hard to guarantee sample belongs to sender "Genetic testing should be delivered within the framework of health care, test results should be reported back to the referring health-care professional, clinical use should be an essential criterion, and appropriate counseling before and after the test should be available."
- Speicher Outcomes Carriers: Implications for entire family Problems Familial clustering doesn't mean genes are involved - high rate of Alzheimer's in old age APOE shouldn't be used as a sole diagnostic tool because it lacks enough specificity, but can be useful with clinical criteria Still finding new mutations in PSEN genes - many false negatives, mutations with unknown significance APOE is a susceptibility gene - contributes to causation under certain circumstances 50% e4 carriers never get disease, 30-60% without e4 still get AD Superimposition - blend ideas about genetics and heredity with previous beliefs about risk/inheritance Risk Belief of high risk based on family history, not actual risk Subjective knowledge used to predict who in family may have Alzheimer's Coping Attempts to distance self from family history Emphasize control over genes Lifestyle changes Genes seen as unstable entities, susceptible to modification by environment Trait anxiety can lead to higher anxiety later on Higher perceived coping ability, more cancer thoughts, previous colonoscopy attendance Screening Fear of cancer higher in carriers, but decreased over time Resolve uncertainty Good screening/detection options Feel more in control - lower distress than with BRCA Reduced stress if motive was to reduce uncertainty Reduced stress if motive was to reduce uncertainty Low in optimism and self-esteem - more likely to be anxious after a year Ways of Responding Chronic dysfunction - consistent pattern of distress
Recovery - initial elevations in distress, then back to norm Resilience - individuals' ability to maintain stable and healthy levels of functioning after a traumatic event Delayed reaction - initially show moderate distress, followed by gradual increase Majority in study were resilient, minority chronically dysfunctional Some delayed reaction - surveillance may begin to distress participant later on Hope (agency, goals, pathways) predicts resilience Lack of perceived control correlates with less screening Affected by age Younger adults influenced by relatives their age getting screened, pressure from relatives Decreases in CRCthoughts, depression Short term decreases in anxiety Short term increase of thoughts about CRC Reductions in distress/depression
Initial inflation Increased access to genetic information Anonymity Less potential for stigmatization Increased risk:
Unnecessary prophylactic surgery
Increased anxiety Decreased risk:
Reduced surveillance Risk from APOE varies with gender Not very accurate - testing of asymptomatic people can be pointless and create worry Individual may discover information they aren't prepared for or don't want Can be helpful with a qualitative interpretation Many do interpret results correctly on their own Result Outcomes Misinterpretation of results Advertising Not necessarily appropriate because few carry mutations advertised Reaches groups not at risk, increasing demand BRCAnalysis campaign - Myriad Genetics
Increases in number of low-risk patients getting referrals for counseling
Chances low - 1/400
http://video.google.com/videoplay?docid=-3139980008594362595&hl=en Increases number who buy DTC testing Efforts to supply genetic testing kits at drugstores Can cause anxiety BRCA1/2 predictive in women with strong family history, but not if there is no family history Clinical validity - genetic variant must correlate with disease/increased risk of disease Clinical utility - test must provide information helping tested individual No regulation Counseling In one study, 10/38 provided some sort of counseling: information in a report, outsourcing, recommendations prepared by counselors, telephone Many don't offer counseling Results affect more than the individual Problems interpreting tests May be ill-informed about tests they want # of DTC tests has doubled from 2003 to 2011 Around 30 companies sell testing online Tests ranging from serious medical conditions to curiosity tests Other countries have banned access to testing People have less intention to get DTC testing and more negative beliefs about it when exposed to information about its risks and prefer clinical testing instead Websites try to maximize sales DTC vs Clinical Statistics Huntington's Disease Alzheimer's Disease Predictive Testing Direct-to-Consumer Testing Motives Uptake Risks & Benefits total dependency, incontinence, immobility, swallowing, dysfunction Death is generally 10-20 years after onset, but many die to other illnesses first due to the late onset of the disease Profound stages: increasing memory difficulties (including long-term memory), difficulties in language and spatial reasoning, begin to have difficulty with daily living Moderate to severe stages: short-term memory loss, difficulty with complex tasks, depression Early stages: Age of onset: 30s-60s, but rare before 60 APOEe4 is risk factor, APOE2 is protective factor e2 allele associated with decreased risk of AD and cardiovascular disease and increased longevity e4 allele associated with increased risk of AD (3-8% in mid 70s, lifetime 15%) and cardiovascular disease and decreased longevity need to know future planning No more anxiety, depression, distress than those who didn't get tested Slightly reduced stress at 6 and 12 months Survival guilt Non-carriers: 10% after 60 10% develop before 20 dementia difficulty speaking, swallowing, maintaining balance loss of speed and flexibility of mental activities, which progresses to impairments in thinking and reasoning loss of abilities to process information and make judgements may have depression, behavior changes, mania, OCD Knowledge can affect perceived risk Appraisal of testing difficulty as threatening, low control, and seeing self manage testing ineffectively increases risk Secondary appraisal: evaluation of coping resources and options to determine if individual can overcome threat Presence of children associated with more distress Had higher levels of distress than partners of non-carriers After testing, attention is focused on carriers, not partners Partners seek less support than carriers Partner's loss is very ambiguous Used less problem solving and more passive-regressive and avoiding behavior to cope May use less denial than carriers Relationship imbalance - caregiving Mourning for anticipated loss of normal future, carrier Partners' main reason for testing was planning for future More post-test distress/poorer quality of life than carriers Differences Loss of Future Distress & Coping 27% non-carriers had inefficient coping compared to 18% carriers Internal - belief in having control - confront problems directly. Less distress. External - helplessness, distress Denial is an unconscious psychological defense that can bring relief and comfort but can prevent adjustment. History of adverse events associated with adverse events after testing Most events occurred within a year of results - long-term support Increased risk group showed more events like suicide than decreased risk group Risk factors: increased risk result, prior psychological history, and unemployment HD has largest frequency of suicide, attempts, and psychiatric hospitalization after predictive testing (0.97%) Ovarian cancer is one of the more serious gynecological cancers 4th highest cause of cancer deaths for women Women generally know more about breast cancer risk factors, symptoms, and curability more than knowledge about genetic risk. More knowledge about cancer = higher perceived risk. Religion impacts screening behaviors...High-risk women with a lower "God" locus of control (less belief in god's control over health) --> follow screening plan better. Younger and more educated African Americans have an increased knowledge about genetic risk factors. Those with a family history are no more knowledgeable than those without a family history. Having a mutation may lead people to not have children in order to not pass on mutation - lose parental role = reduced self-concept Physical self can be altered 'Damaged' in reproductive role Words like 'mutation' and 'abnormal' suggest negativity. Early, surgically induced menopause Avoidance coping styles (least useful): focusing on and venting of emotions, behavioral/mental disengagement Emotion-focused coping styles: seeking emotional social support, positive reinterpretation, acceptance, denial, religion Multiple losses in the family can lead to negative self-concept. Ability to construct possible future selves can help to recover from a significant event Coping processes (engaging with stress of testing) are most predictive of benefit finding BRCA is an anticipated stressor, not an immediate stressor like a cancer idagnosis Carriers with a previous cancer diagnosis reported more benefit finding than unaffected carriers and non-carriers. Potential positive changes: more support from family, awareness of how precious life is, increased sense of control (treatment options) Causes reconstruction of life view and personal strength Secondary: evaluation of coping resources and options to see if they will be enough to overcome threat If even is judged negative, it will be evaluated in terms of the harm it has done and its future threat Monitors focus on present, reassess priorities, think positive, and try to have a healthy lifestyle including surveillance. Blunters avoid cues and decrease surveillance. Can be present without symptoms Risk increases with age Can present anywhere in large intestine. 40% have a regional disease involving nearby lymph nodes. 25% have distant metastases @ diagnosis. Most are diagnosed between 60-75. Accounts for 10% of cancer deaths.