Genetic counseling at our center involves a geneticist, a physician, a genetic counselor (nurse), a psychologist and a secretarial service. An engineer is responsible for the computer management of medical data. After an initial contact by telephone patients are asked to describe their genealogical tree, indicating cancers and other possible hereditary diseases. In an initial consultation, patients present themselves and their pedigree to the genetic counselor, who helps the patients complete their genealogical tree and informs them about hereditary cancer risk and the genetic testing process. The patients then meet the geneticist, who evaluates the hereditary risk. If genetic testing is indicated, the patients are provided with further medical information and a first-blood sample is taken (a second one is required later if a mutation is found). An information booklet concerning the type of familial risk is offered, and a letter is sent to their general practitioner (or other physician if they wish) to inform them about the onset of genetic testing.
Once the analysis is completed, the patient returns for a second pair of consultation, with the genetic counselor and then with the geneticist or the physician. The genetic counselor updates the pedigree, if needed, with the patients and evaluates their global knowledge and their capacity to cope with the announcement of the result. Two types of consultation are possible with the geneticist/physician:
- An individual mode where the result is given to the person alone.
- A familial mode where the results of the genetic analysis (positive or negative) are given to several members of a family, but without telling who is a carrier. This type of consultation is indicated when the whole result is negative or when the carrier of the found mutation is not present. Actually, this latter mode is less and less used as it has shown some limits.
Personal cancer risk is explained and recommendations are given concerning suitable medical supervision and the necessity to encourage relatives to ask for genetic testing in order to be benefited from effective screening and prevention. A final letter is then addressed to the patient(s) and his/her designated doctor(s). All along the research, the recipients are informed that they can always ask for a consultation with the psychologist.
Database of familial information
An updated version of SEM software16
was used to extract a representative sample of probands and relatives from our genetic consultation database. This version stores standard information, including gender, birth date, address, marital status and also medical data such as date of past consultations, type of mutation (if any), cancer (if any) location and age at diagnosis, disease status and date of death.
Development of the questionnaire
A committee of experts (geneticists, physicians, psychologists, nurses and statistician) was designated to elaborate a questionnaire that could answer to defined questions. The face and content validity was assessed by a group of oncologists, radiotherapists, surgeons, nurses, health supervisors, secretaries, biologists and patients. Questions were either direct (addressed to the respondent) or indirect (general purpose, use of the third person) and sometimes partially redundant to facilitate cross-controls.
Questions were grouped into several sections:
- Marital status, children, activity, educational level and cancer history
- Date of last genetic counseling session
- Present compliance with medical recommendations
- General knowledge of the meaning of hereditary predisposition to cancer
- Necessary steps for a new family member to obtain genetic testing
- General knowledge about screening, genetic mutations and their consequences
- How transmission of genetic information is done or inhibited within the family
- Difficulties in putting recommendations into practice
- Remarks on the breast/ovarian cancer information booklet
In all, 10 questions concerned the section ‘current compliance with medical recommendations', and presented a series of possible examinations (mammography, MRI, clinic, ultrasound, trans-vaginal ultrasound, cervical smear, aspirative smear, colonoscopy, occult bleeding, blood markers dosage, etc) for which the subject was asked to specify the recommended frequency in relationship with his/her cancer risk. Available answers ranged from 6 months to never, including 6, 12, 18 and 24 months. Correctness scoring was adjusted according to the history of cancer of each subject. Answers were counted as correct if they applied to the subject.
The fourth section tested knowledge of the meaning of hereditary predisposition. Seven questions proposed degrees of agreement with various propositions, including
- a supplementary risk of cancer for yourself, your family;
- predisposition to a certain kind of cancer for yourself, your family;
- a diagnosis of cancer;
- a vulnerability to environmental factors;
- a risk of infection.
The last three topics were considered false, although some could argue whether mutations associated with cancer represent a possible weakness to environmental threats.
The fifth section, of 11 questions, grouped propositions concerning the necessary steps for someone to start a personal genetic inquiry. One or two consultations with a geneticist were the first questions. Different types of biological samples were then proposed: saliva, urine, skin, blood (one or two samples), hair, semen (for men) and lumbar puncture. A scan or RMI was the last item. According to our actual genetic testing process, good answers were two consultations and two blood samples, as a mutation discovery must be certified by identical results on two different blood samples obtained at two different times. But one consultation and a single blood sample were also rated correct since years ago, this was the recommendation.
The sixth chapter entitled ‘General knowledge about screening, genetic mutations and their consequences', comprised 24 proposals, all presented with a Likert scale enabling to quote the degree of agreement. They were labeled as possibly true or false sentences, as for example:
- Some cancers are hereditary.
- If one has a familial predisposition, it means he would necessarily have a cancer.
- A genetic mutation transmits itself more often between a parent and children of the same sex.
- The cancer is not hereditary, but the predisposition is.
- Obtaining my personal genetic test can increase my cancer risk.
Further sections are not treated in this report.
Inclusion and response diagram
After approval by the local ethics committee, the anonymous questionnaire was mailed to a representative subset of 579 probands and relatives from our database, with a letter to introduce the survey signed by the geneticist. In order to limit heterogeneity, only breast/ovarian and colon cancer risks were targeted.
The pre-selection search of the database identified for living persons registered in families at risk of breast, ovarian and/or colon cancer, with a genetic counseling consultation in the last 10 years, older than 18 years and with a known address. A randomization was performed within the non-mutated breast/ovarian group in order to reduce its size, but in other groups we kept all the subjects in order not to reduce analysis power. So, no exclusions were made in mutation-carrier groups, as these categories were smaller (). To assess possible non-response bias, a second mailing was sent to one third of a randomized subset of non-respondents.
Flowchart of survey accrual. Numbers indicate responses/questionnaires sent.
Survey design and statistics
The number of persons contacted was calculated to provide±5% precision in the results (range of the 95% confidence interval), which required 400 responses. A final response rate of 58% was achieved with 337 answered mails over 579, thus 63 fewer than the 400 expected. The accuracy of the main results was therefore±5.3%, which remained acceptable.
Answers to the survey questions are treated in a quantitative or qualitative manner as appropriate. Most were scored on four-level Likert scales (from total disagreement to complete agreement) in order to force respondents to choose one side or the other (with a five-level scale, many persons select the median class). Likert scale results were transformed into scores and confidence intervals calculated, using 0 for total disagreement, 1 for mild disagreement, 2 for mild agreement and 3 for maximal agreement.
When answers reflected a state of knowledge from other sources, or when they were compared with information given during oncogenetic counseling, they generally were either right or wrong, making it possible to group questions of a section and compute an average ‘grade' over 10 that measured the correctness of the subjects' answers. The larger the gap was between this grade and the optimum of 10, the less knowledge the subject retained for the topic. Sections containing medical or practical information were treated in this way.
For statistical testing, standard repartition parameters (numbers, means, medians, standard deviations and ranges) were calculated. Tests used to study the link between pairs of variables consisted of χ2, one-way ANOVA or Kruskal–Wallis H test (depending on normality of distributions and/or difference of variances) and Pearson's correlation coefficient or Spearman's rank tests. Intra-subject comparisons were performed using paired tests.
-values less than 0.05 were used as the threshold for significance. Statistical tests were performed using the SEM software.16