Patient preferences regarding recontact by cancer genetics clinicians.

BACKGROUND: Ongoing advances in cancer genetics lead to new opportunities for early disease detection, predictive genetic testing and potential interventions. Limited information exists on patient preferences concerning recontact to provide updated information. We evaluated colon cancer genetics patient preferences concerning recontact about advances in medical genetics. METHODS: Information was mailed to 851 individuals seen at the Colon Cancer Risk Assessment Clinic at the Johns Hopkins Hospital and to participants in a colon cancer gene testing study seen during an 8-year period. Information provided included description of advances in gene testing technology, discovery of MSH6 and MYH genes, detailed fact sheets and a survey of patient preferences for notification and potential uses of new information. RESULTS: Most patients wanted an ongoing relationship with genetics providers (63%), reinitiated by genetics providers (65%) and contact only with information specifically relevant to them (51%). Most preferred personalized letters as the means of contact (55%). Reasons for and against recontact and circumstances in which individuals would pursue additional genetic testing were also tabulated. There were few statistically significant differences in the responses between clinic and study participants. CONCLUSION: Patients evaluated in a colon cancer risk assessment clinic want updated information at a rate similar to those who participated in a colon cancer gene testing study. These findings have implications for the consultative nonlongitudinal nature of such clinics and suggest patient preferences for personally-tailored information could be labor intensive.

Frequency and spectrum of cancers in the Peutz-Jeghers syndrome.

BACKGROUND: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited. EXPERIMENTAL DESIGN: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations. RESULTS: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference chi2 = 0.62; 1 df; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk. CONCLUSIONS: The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome and management recommendations.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease caused by germline mutation of the serine threonine kinase 11 and characterized by hamartomatous polyps in the gastrointestinal tract and mucocutaneous melanin pigmentation. Patients with PJS are at increased risk for common and unusual types of gastrointestinal and nongastrointestinal tumors. This review analyzes currently available literature and describes the clinical characteristics of PJS, assesses the risk of malignancy in this disorder, and delineates management and surveillance recommendations for affected individuals.

Genetic counseling outcomes: perceived risk and distress after counseling for hereditary colorectal cancer.

Genetic counseling may turn risk information into cancer prevention behavior by modifying health beliefs and cancer-related distress. We assessed the effect of genetic counseling on these factors in 101 adult first-degree-relatives of colorectal cancer patients from families with known or suspected hereditary nonpolyposis colorectal cancer. Before counseling and once afterward, subjects completed self-report measures of perceived lifetime risk and cancer-distress. Most persons overestimated their cancer risk, and higher perceived risk was associated with believing that colorectal cancer cannot be prevented. Individual perceived risk changed after counseling, although mean perceived risk was unchanged. After adjusting for baseline risk, older persons and those with higher estimated objective cancer risk had larger postcounseling decreases. Distress after counseling was positively correlated with baseline distress and anxiety symptoms, and inversely correlated with tolerance for ambiguity. The findings suggest counseling interventions that should increase the likelihood of screening and offer hypotheses for future research.

Oral contraceptives and polyp regression in familial adenomatous polyposis.

Epidemiologic and experimental reports suggest that female hormones protect against the development of colorectal cancer, but studies are limited. We describe a patient in the placebo arm of a 4-year primary chemoprevention trial who developed adenomatous polyps and then had eradication of polyps after the administration of oral contraceptives. No change in the prostaglandin levels in the colonic mucosa was noted after polyp elimination, making nonsteroidal anti-inflammatory drug ingestion unlikely as a cause. This report represents the regression of colorectal adenomas with the use of estrogen/progesterone compounds.

Prostanoids, ornithine decarboxylase, and polyamines in primary chemoprevention of familial adenomatous polyposis.

BACKGROUND & AIMS: Familial adenomatous polyposis because of germline mutation of the adenomatous polyposis coli gene is characterized by development of colorectal adenomas and, ultimately, colorectal cancer. The usefulness of colorectal mucosal compounds to predict the effect on adenoma development of primary chemoprevention with the nonsteroidal anti-inflammatory drug sulindac was evaluated. METHODS: A randomized, double-blind, placebo-controlled study of 41 subjects genotypically affected with familial adenomatous polyposis but phenotypically unaffected was conducted. Patients received either sulindac or placebo for 48 months, and development of new adenomas was evaluated. The levels of 5 prostanoids, ornithine decarboxylase, and polyamines were measured serially in normal-appearing rectal mucosa. RESULTS: There were no statistically significant differences between treatment groups in baseline levels of prostanoids, ornithine decarboxylase, or polyamines. At conclusion of the study, 4 of 5 prostaglandin levels were statistically significantly lower in the sulindac group than in the placebo group. Among the subset of patients taking sulindac, 3 of 5 prostaglandin levels were statistically significantly lower in patients who were polyp free than in those who developed polyps. By contrast, there were no statistically significant differences in ornithine decarboxylase or polyamines between treatment groups or in those on sulindac who were polyp free compared with those who developed polyps. CONCLUSIONS: Colorectal mucosal prostaglandin levels, but not ornithine decarboxylase or polyamines, may be valuable biomarkers to assess appropriate drug dosage and medication compliance in patients undergoing primary chemoprevention therapy with sulindac. Reduction of mucosal prostaglandin levels may be necessary to achieve chemopreventive benefit from this agent.

Genetic testing for hereditary colorectal cancer in children: long-term psychological effects.

Children who carry a gene mutation for familial adenomatous polyposis are virtually certain to develop colorectal cancer without annual endoscopic screening and a colectomy when polyps appear. Predictive genetic testing can identify children who need regular surveillance. While the medical benefits of genetic testing are clear, the psychological effects have not been well studied. We evaluated the long-term psychological effects of genetic testing in 48 children and their parents. In each family, one parent was a known APC gene mutation carrier. Before genetic testing, and three times afterward, participants completed measures of psychological functioning, which, for children, included depression and anxiety symptoms, and behavior problems and competencies. Parents completed a measure of depression symptoms. Data were collected at 3-, 12-, and 23-55 months after disclosure. Twenty-two children tested positive; 26 children tested negative. Mean length of follow-up was 38 months. There were no clinically significant changes in mean psychological test scores in children or parents, regardless of the children's test results or the sex of the affected parent. However, the group of children who tested positive and had a mutation-positive sibling showed significant, but subclinical, increases in depression symptoms. Furthermore, several individual mutation-negative children with a positive sibling had clinical elevations in anxiety symptoms at one or more follow-up. Behavior problems declined for all groups, and behavior competence scores remained unchanged. We conclude that most children do not suffer clinically significant psychological distress after testing. However, because some children showed clinically significant anxiety symptoms, long-term psychological support should be available to those families with both mutation-positive and mutation-negative children, and with multiple mutation-positive children. Our findings should call for a multidisciplinary approach to genetic testing for children.

Primary chemoprevention of familial adenomatous polyposis with sulindac.

BACKGROUND: Familial adenomatous polyposis is caused by a germ-line mutation in the adenomatous polyposis coli gene and is characterized by the development of hundreds of colorectal adenomas and, eventually, colorectal cancer. Nonsteroidal antiinflammatory drugs can cause regression of adenomas, but whether they can prevent adenomas is unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled study of 41 young subjects (age range, 8 to 25 years) who were genotypically affected with familial adenomatous polyposis but phenotypically unaffected. The subjects received either 75 or 150 mg of sulindac orally twice a day or identical-appearing placebo tablets for 48 months. The number and size of new adenomas and side effects of therapy were evaluated every four months for four years, and the levels of five major prostaglandins were serially measured in biopsy specimens of normal-appearing colorectal mucosa. RESULTS: After four years of treatment, the average rate of compliance exceeded 76 percent in the sulindac group, and mucosal prostaglandin levels were lower in this group than in the placebo group. During the course of the study, adenomas developed in 9 of 21 subjects (43 percent) in the sulindac group and 11 of 20 subjects in the placebo group (55 percent) (P=0.54). There were no significant differences in the mean number (P=0.69) or size (P=0.17) of polyps between the groups. Sulindac did not slow the development of adenomas, according to an evaluation involving linear longitudinal methods. CONCLUSIONS: Standard doses of sulindac did not prevent the development of adenomas in subjects with familial adenomatous polyposis.

Impact of genetic counseling and testing on colorectal cancer screening behavior.

One goal of cancer genetic counseling is to improve early detection and prevention of cancers by identifying individuals at risk and providing screening recommendations. This study determined the impact of genetic counseling and testing on patient's post-genetic risk assessment colorectal cancer screening behaviors. Follow-up data from patients seen August, 1996, through May, 1998, at the Johns Hopkins Cancer Risk Assessment Clinic were analyzed. Eligible patients included those without cancer who were due for a colon examination by the time of follow-up, based on recommendations given during genetic risk assessment (GRA). We analyzed the role of gender, age, time since GRA, prior screening, genetic testing decision, mutation status, and post-GRA screening. Of 65 patients evaluated, 50 (76.9%) had undergone at least one endoscopic colon exam prior to visiting the Cancer Risk Assessment Clinic. At the time of GRA, 37 of 65 (56.9%) were overdue for a colon exam and at the time of follow-up, 15/65 (23.1%) were past due (p < 0.001). Patients with mutation-positive genetic tests were more likely to adhere to screening guidelines than those with negative gene tests (100% vs. 40.5%, p = 0.05). Genetic counseling and testing increases overall patient adherence with recommended colon screening, especially for those with positive genetic test results. However, patients with negative results may receive false reassurance about cancer risks and fail to follow recommended screening. Emphasis should be placed on the importance of screening even when genetic test results are negative.