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C Lerman

Publications and source records attributed to C Lerman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinical impact of molecular genetic diagnosis, genetic counseling, and management of hereditary cancer. Part II: Hereditary nonpolyposis colorectal carcinoma as a model.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common hereditary form of colorectal carcinoma (CRC) and may account for 5-10% of the total CRC burden. The discovery of DNA mismatch repair (MMR) genes, inclusive of hMSH2, hMLH1, hPMS2, and hMSH6, has enabled the identification of who has and who does not have inordinately increased susceptibility to CRC as well as a litany of extracolonic cancers. Mutation testing has focused on hMSH2 and hMLH1, the most common mutations in HNPCC. The protocol for DNA testing and DNA-based genetic counseling is described in Part I of this study. One hundred ninety-nine bloodline relatives were tested and counseled from five hMLH1 and two hMSH2 families. Their major reason for seeking genetic counseling and DNA testing was to inform their children and other loved ones of their mutation status. Those who sought counseling overestimated their risk for inheriting the mutation and showed a high rate of interest in prophylactic surgery, and many were greatly concerned about insurance discrimination. Knowledge about HNPCC, its molecular genetic diagnosis, surveillance and management opportunities, and genetic counseling implications are still emerging, all in the face of a greater need for physician education regarding all facets of hereditary cancer.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2.

BACKGROUND: Early age at first full-term pregnancy and increasing parity are associated with a reduced risk of breast cancer. However, whether pregnancy decreases the risk of early-onset hereditary breast cancer is unknown. There is concern that pregnancy may increase breast-cancer risk in carriers of BRCA1 and BRCA2 germline mutations. We aimed to establish whether pregnancy is a risk factor for hereditary breast cancer. METHODS: We did a matched case-control study of breast cancer in women who carry deleterious BRCA1 or BRCA2 mutations. Cases were carriers who developed breast cancer by age 40 years, and controls were carriers of the same age without breast cancer, or who were diagnosed with breast cancer after age 40 years. Women who had undergone preventive mastectomy, hysterectomy, or oophorectomy, or who were diagnosed with ovarian cancer before the age at which breast cancer was diagnosed in the matched case were excluded. Information about pregnancies and pregnancy outcome was derived from a questionnaire completed by women in the course of genetic counselling. FINDINGS: A higher proportion of cases than controls had had a full term pregnancy (173/236 vs 146/236; odds ratio 1.71 [95% CI 1.13-2.62], p=0.01). The mean number of births was also greater for cases than for controls (1.62 vs 1.38, p=0.04). The risk increased with the number of births and did not diminish with time since last pregnancy. There were no significant differences in age at first birth or age at last birth between cases and controls. INTERPRETATION: Carriers of the BRCA1 and BRCA2 mutations who have children are significantly more likely to develop breast cancer by age 40 than carriers who are nulliparous. Each pregnancy is associated with an increased cancer risk. An early first pregnancy does not confer protection for carriers of BRCA1 or BRCA2 mutations.

Adult↗
PubMed1999

Genetic testing in families with hereditary nonpolyposis colon cancer.

CONTEXT: Genetic testing for hereditary nonpolyposis colon cancer (HNPCC) is available, but the rates of acceptance of testing or barriers to participation are not known. OBJECTIVE: To investigate rates and predictors of utilization of genetic testing for HNPCC. DESIGN: Cohort study conducted between July 1996 and July 1998. SETTING: Hereditary nonpolyposis colon cancer family registry. PARTICIPANTS: Adult male and female members (n = 208) of 4 extended HNPCC families contacted for a baseline telephone interview. INTERVENTIONS: Family education and individual genetic counseling. MAIN OUTCOME MEASURE: Participant acceptance of HNPCC test results. RESULTS: Of the 208 family members, 90 (43%) received test results and 118 (57%) declined. Of 139 subjects (67%) who completed a baseline telephone interview, 84 (60%) received test results and 55 (40%) declined. Of the 84 subjects who received test results, 35 (42%) received information indicating that they had HNPCC-associated mutations and 49 (58%) that they did not. Test acceptors had higher education levels (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.49-5.61) and were more likely to have participated in a previous genetic linkage study (OR, 4.30; 95% CI, 1.84-10.10). The presence of depression symptoms significantly reduced rates of HNPCC test use (OR, 0.34; 95% CI, 0.17-0.66). Although rates of test use were identical among men and women, the presence of depression symptoms resulted in a 4-fold decrease in test use among women (OR, 0.25; 95% CI, 0.08-0.80) and a smaller, nonsignificant reduction among men (OR, 0.49; 95% CI, 0.19-1.27). CONCLUSIONS: Despite having significantly elevated risks of developing colon cancer, a relatively small proportion of HNPCC family members are likely to use genetic testing. Barriers to test acceptance may include less formal education and the presence of depression symptoms, especially among women. Additional research is needed to generalize these findings to different clinical settings and racially diverse populations.

Adult↗
PubMed1999

Bilateral prophylactic mastectomy decision making: A vignette study.

BACKGROUND: Little is known about the perception of bilateral prophylactic mastectomy (BPM), and whether perceptions are influenced by a family history of breast cancer. It is also unclear what factors may play a role in selecting BPM for follow-up care. METHODS: Samples of predominantly Caucasian, well-educated women with (n = 129) and without (n = 104) family histories of breast cancer were provided a vignette of a woman at increased risk. They selected one of two follow-up options: (1) clinical breast examination, breast self exam, and annual mammography or (2) BPM. RESULTS: The samples did not differ on the decision to select BPM (29.5% vs 22.1%). The family history sample reported worry about breast cancer as a problem (34.4%) more often than women with no history (15.7%). Multivariate analysis found worry and estimated 10-year risk of the woman in the vignette as significant predictors of selecting BPM. CONCLUSIONS: Approximately 25% of our sample selected BPM as the preferred option. The majority supported the need to discuss BPM among women at increased risk. Finally, both factors associated with the selection of BPM (worry, risk assessment) are potentially amenable to psychosocial or educational approaches. There is a clear need for assessment of worry and risk perception prior to surgical decision making.

Adult↗
PubMed1999

An update on DNA-based BRCA1/BRCA2 genetic counseling in hereditary breast cancer.

The identification of BRCA1 and BRCA2 mutations has enabled physicians to identify persons at high risk for carcinoma of the breast and ovary in hereditary breast-ovarian cancer (HBOC) families. Many physicians have limited knowledge about the effective translation of these new discoveries into clinical practice settings. This problem is further confounded by the limited number of genetic counselors who have experience with cancer genetics. Genetic counseling about DNA test results was provided to 420 patients from 37 HBC/HBOC families. Descriptive data were collected and recorded about their responses to questions posed immediately before and after test results were disclosed. Findings disclosed a significant tendency of patients to overestimate rather than underestimate their risk (P < .001) prior to receiving results. The chief reason for declining to receive results was fear of insurance discrimination. The primary reason that patients sought test results was for their children. Most women reported that, if testing identified them as mutation carriers, they would consider lifetime surveillance and prophylactic surgery. Responses to DNA test results were varied and often unpredictable. Counseling by an appropriately educated and skilled professional is essential to assist people in making decisions regarding testing and health management.

Adult↗
PubMed1999

Evidence suggesting the role of specific genetic factors in cigarette smoking.

Twin studies suggest that propensity to smoke and ability to quit smoking are influenced by genetic factors. As a means of investigating the risk of smoking associated with genetic polymorphisms in the dopamine transporter (SLC6A3) and the D2 dopamine receptor (DRD2) genes, a case-control study of 289 smokers and 233 nonsmoking controls and a case series analysis of smokers were conducted. A significant effect for SLC6A3 and a significant gene-gene interaction were found in a logistic regression model, indicating that individuals with SLC6A3-9 genotypes were significantly less likely to be smokers, especially if they also had DRD2-A2 genotypes. Smokers with SLC6A3-9 genotypes were also significantly less likely to have started smoking before 16 years of age and had prior smoking histories indicating a longer period of prior smoking cessation. This study provides preliminary evidence that the SLC6A3 gene may influence smoking initiation and nicotine dependence.

Adult↗
PubMed1999

Intron variants of the p53 gene are associated with increased risk for ovarian cancer but not in carriers of BRCA1 or BRCA2 germline mutations.

Two biallelic polymorphisms in introns 3 and 6 of the p53 gene were analysed for a possible risk-modifying effect for ovarian cancer. Germline DNA was genotyped from 310 German Caucasian ovarian cancer patients and 364 healthy controls. We also typed 124 affected and 276 unaffected female carriers with known deleterious BRCA1 or BRCA2 germline mutation from high-risk breast-ovarian cancer families. Genotyping was based on PCR and high-resolution gel electrophoresis. German ovarian cancer patients who carried the rare allele of the MspI restriction fragment length polymorphism (RELP) in intron 6 were found to have an overall 1.93-fold increased risk (95% confidence internal (CI) 1.27-2.91) which further increased with the age at diagnosis of 41-60 years (odds ratio (OR) 2.71, 95% CI 1.10-6.71 for 41-50 and OR 2.44, 95% CI 1.12-5.28 for 51-60). The 16 bp duplication polymorphism in intron 3 was in a strong linkage to the MspI RFLP. In BRCA1 or BRCA2 mutation carriers, no difference in allele frequency was observed for carriers affected or unaffected with ovarian cancer. Our data suggest that intronic polymorphisms of the p53 gene modify the risk for ovarian cancer patients but not in carriers with BRCA1 or BRCA2 mutations.

Adolescent↗
PubMed1999

Risk communication in genetic testing for cancer susceptibility.

Risk communication is an integral part of genetic counseling and testing for cancer susceptibility. This paper reviews the emerging literature on this topic. Three relevant aspects of risk communication are addressed: communication of individual risk, communication of the risks inherent in genetic testing, and family communications related to risk. These studies suggest that (a) most individuals with some family history of cancer, including those at low to moderate risk, overestimate their personal cancer risk; (b) awareness of the risks of genetic testing is limited; (c) decision making about genetic testing is influenced strongly by exaggerated perceptions of personal cancer risk and less so by perceptions of the risks of genetic testing; (d) perceptions of personal risk of cancer are resistant to standard education and counseling approaches; (e) psychologic distress and coping processes influence the processing of risk information and subsequent decision making in genetic testing; and (f) family influences play an important role in risk awareness, genetic testing decisions, and outcomes. To study these issues further, new theoretical models and measures of risk perceptions need to be developed. Both observational and experimental methods should be used to examine both the content and process of risk communication in cancer genetic counseling and testing. Emotional, familial, and sociocultural influences on the risk communication process require special attention.

Communication↗
PubMed1999

Patterns of breast cancer screening among lesbians at increased risk for breast cancer.

BACKGROUND: Women with a family history of breast cancer (i.e., in a mother, sister or daughter) are at increased risk for this disease. Previous data also suggest that lesbians are at increased risk for breast cancer. While the screening behaviors of women with a family history have been described, little is known about factors that influence screening behaviors of lesbians with the same risk factor profile. PURPOSE: The purpose of this study was to characterize the perceptions of susceptibility to breast cancer and describe factors that influence adherence to breast cancer screening guidelines in a sample of lesbians with a first-degree relative with a diagnosis of breast cancer. METHODS: Structured telephone interviews were conducted on a sample of 139 self-identified lesbians who had a first-degree relative with a diagnosis of breast cancer, were between the ages of 35 to 75 and had no previous history of cancer. Cross-sectional data obtained, included socio-demographics, breast cancer risk factors, breast cancer screening patterns, breast cancer perceptions, worries, and knowledge, and barriers and access to health care factors. Individual subject characteristics were examined for their association with adherence to mammography guidelines followed by a multivariate analysis to evaluate the most important combinations of factors. Outcome measures were age-specific adherence to ACS guidelines for both mammography and overall adherence (i.e., mammography, clinical breast examination and breast self-examination). RESULTS: The 139 lesbians interviewed for this study were young (mean age = 43), almost exclusively white (94%), highly educated (78% = college graduate and beyond), and partnered (68%). In the bivariate analysis of individual factors, being employed and reporting breast cancer worries were significantly and positively associated with adherence to mammography guidelines. Higher income and insurance type were significantly associated with mammography adherence. No factors were significantly associated with overall adherence. Multivariate logistic regression analyses revealed that only income level and degree of breast cancer worries were significantly and positively associated with mammography adherence. However, since there was a high correlation between income level and employment status, a regression model with employment status and worry was also significantly related to mammography adherence. CONCLUSIONS: In lesbians who are at an increased risk for breast cancer because of family history, breast cancer worries may motivate, rather than deter, adherence for mammography use. High income levels also appear to enable adherence in this population. IMPLICATIONS: Additional studies are needed to validate these findings, identify the prevalence of lesbians in general samples of women at increased risk for breast cancer, and prospectively test lesbian sensitive educational intervention strategies designed to facilitate adherence to mammography screening guidelines in this population.

Adult↗
PubMed1999

A randomized trial of breast cancer risk counseling: the impact on self-reported mammography use.

OBJECTIVES: We evaluated the impact of individualized breast cancer risk counseling on mammography use among women at risk for breast cancer. METHODS: Participants (n = 508) were randomized to the breast cancer risk counseling intervention or a general health education control intervention, and 85% completed follow-up. RESULTS: In multivariate modeling, a significant group-by-education interaction demonstrated that among less-educated participants, breast cancer risk counseling led to reduced mammography use. There was no intervention effect among the more-educated participants. CONCLUSIONS: These results suggest that standard breast cancer risk counseling could have an adverse impact on the health behaviors of less-educated women.

Adult↗
PubMed1999

Correlates of intentions to obtain genetic counseling and colorectal cancer gene testing among at-risk relatives from three ethnic groups.

OBJECTIVES: An understanding of factors associated with interest in genetic counseling and intentions to obtain colorectal cancer susceptibility testing is an important foundation for developing education, counseling, and genetic services and policies. MATERIALS AND METHODS: A survey was mailed to first-degree relatives of patients diagnosed with colorectal cancer. The respondents (n = 426, 77% response rate) are siblings and adult children of Caucasian, Japanese, and Hawaiian ethnicity. Data collection was guided by a conceptual framework and included questions on demographics, family cancer history, predisposing factors (cancer worry, perceived risk, well-being), and enabling factors (decision preferences, social support, and health care factors). Logistic regression analysis on two binary dependent variables (interest in counseling and intentions to get genetic testing) was performed using Generalized Estimating Equations to account for family clusters. RESULTS: Forty-five % of respondents were interested in genetic counseling, and 26% "definitely" intended to get genetic testing for colon cancer when available. For counseling interest, the most important predictors were education, Hawaiian ethnicity, cancer worry, and family support. Cancer worry, perceived risk, and age (older) were directly, and Japanese ethnicity was inversely, associated with testing intentions. CONCLUSIONS: High rates of interest in cancer genetic testing are similar to those found in other studies. Ethnic differences reveal a paradox between objective population risk (higher for Japanese) and greater concerns (among Hawaiians). The substantial lack of awareness of family history warrants further research. Culturally sensitive education and counseling are needed for managing the likely high demand for personalized information about hereditary cancer risk.

Adult↗
PubMed1999

Racial differences in testing motivation and psychological distress following pretest education for BRCA1 gene testing.

OBJECTIVES: We conducted a randomized trial to investigate racial differences in response to two alternate pretest education strategies for BRCA1 genetic testing: a standard education model and an education plus counseling (E + C) model. MATERIALS AND METHODS: Two hundred twenty-eight Caucasian women and 70 African American women with a family history of breast or ovarian cancer were contacted for a baseline telephone interview to assess sociodemographic characteristics, number of relatives affected with cancer, and race before pretest education. Outcome variables included changes from baseline to 1-month follow-up in cancer-related distress and genetic testing intentions, as well as provision of a blood sample after the education session. RESULTS: African American women were found to differ significantly from Caucasian women in the effects of the interventions on testing intentions and provision of a blood sample. Specifically, in African American women, E + C led to greater increases than education only in intentions to be tested and provision of a blood sample. These effects were independent of socioeconomic status and referral mechanisms. In Caucasian women, there were no differential effects of the interventions on these outcomes. Reductions in cancer-specific distress were evidenced in all study groups. However, this decrease, although not significantly different, was smallest among African American women who received E + C. CONCLUSIONS: In low- to moderate-risk African American women, pretest education and counseling may motivate BRCA1 testing. Further research is needed to explore the mechanisms of impact of the alternate pretest education strategies and to increase the cultural sensitivity of education and counseling protocols.

Adolescent↗
PubMed1998

Effect of smoking on breast cancer in carriers of mutant BRCA1 or BRCA2 genes.

BACKGROUND: Smoking has carcinogenic effects, and possibly antiestrogenic effects as well, but it has not been found to be a risk factor for breast cancer in women in the general population. However, hereditary breast cancer is primarily a disease of premenopausal women, and interactions between genes and hormonal and environmental risk factors may be particularly important in this subgroup. METHODS: We conducted a matched case-control study of breast cancer among women who have been identified to be carriers of a deleterious mutation in either the BRCA1 or the BRCA2 gene. These women were assessed for genetic risk at one of several genetic counseling programs for cancer in North America. Information about lifetime smoking history was derived from a questionnaire routinely administered to women who were found to carry a mutation in either gene. Smoking histories of case subjects with breast cancer and age-matched healthy control subjects were compared. Odds ratios for developing breast cancer were determined for smokers versus nonsmokers by use of conditional logistic regression for matched sets after adjustment for other known risk factors. RESULTS: Subjects with BRCA1 or BRCA2 gene mutations and breast cancer were significantly more likely to have been nonsmokers than were subjects with mutations and without breast cancer (two-sided P = .007). In a multivariate analysis, subjects with BRCA1 or BRCA2 mutations who had smoked cigarettes for more than 4 pack-years (i.e., number of packs per day multiplied by the number of years of smoking) were found to have a lower breast cancer risk (odds ratio = 0.46, 95% confidence interval = 0.27-0.80; two-sided P = .006) than subjects with mutations who never smoked. CONCLUSIONS: This study raises the possibility that smoking reduces the risk of breast cancer in carriers of BRCA1 or BRCA2 gene mutations.

Breast Neoplasms↗
PubMed1998

The impact of a brief problem-solving training intervention for relatives of recently diagnosed breast cancer patients.

Previous studies have found high levels of psychological distress in women who have a family history of breast cancer. We evaluated a brief Problem-Solving Training (PST) intervention designed to reduce distress among women with a first-degree relative recently diagnosed with this disease. Participants were randomly assigned to either the PST group (N = 144) or a General Health Counseling (GHC) control group (N = 197). At baseline, these groups did not differ on any sociodemographic, risk factor, or psychological distress variables. We evaluated the impact of PST, relative to GHC, at the three-month follow-up assessment using a 2 (treatment group) x 2 (time of assessment) mixed factor analysis of variance (ANOVA). Although there were significant decreases in both cancer-specific and general distress in both the PST and GHC groups, the magnitude of these decreases did not differ. However, when PST participants were divided into those who regularly practiced the PST techniques and those who did not, significant differences emerged. Participants who regularly practiced the PST techniques had significantly greater decreases in cancer-specific distress [Impact of Event Scale (IEs) intrusion and avoidance subscales] compared to infrequent practicers and GHC participants. Effects on general distress were not found. Additional studies are needed to identify ways to promote the practice of PST techniques and to evaluate other psychosocial interventions for female relatives of breast cancer patients.

Adaptation, Psychological↗
PubMed1998

Depression and self-medication with nicotine: the modifying influence of the dopamine D4 receptor gene.

This study evaluated whether there are genetic subgroups of depressed individuals who are more or less predisposed to engage in self-medication smoking practices. Smokers (N = 231) completed self-report questionnaires of depression and smoking practices and were genotyped for the dopamine D4 receptor (DRD4) gene. A significant interaction (DRD4 Genotype x Depression) was found for stimulation smoking and negative-affect reduction smoking. Specifically, these smoking practices were significantly heightened in depressed smokers homozygous for the short alleles of DRD4 but not in those heterozygous or homozygous for the long alleles of DRD4. These preliminary results suggest that the rewarding effects of smoking and the beneficial effects of nicotine replacement therapy for depressed smokers may depend, in part, on genetic factors involved in dopamine transmission.

Adult↗
PubMed1998

Genetic counseling and testing for breast-ovarian cancer susceptibility: what do women want?

PURPOSE: To assess preferences for the content and process of genetic counseling and testing for breast-ovarian cancer susceptibility among women at high risk for breast cancer. METHODS: Ninety-eight healthy women who had a family history of breast cancer in at least two first-degree relatives participated in a structured telephone survey that evaluated preferences for type of provider and the content and process of pretest education and posttest genetic counseling. RESULTS: Forty-two percent of women preferred that pretest education be delivered by a genetic counselor, while 22% preferred an oncologist. This preference was positively associated with a desire to discuss psychosocial issues during the session (P = .001). For posttest counseling, 38% of women preferred an oncologist, while 20% preferred a genetic counselor. However, women who desired supportive counseling during this session were significantly more likely to prefer a genetic counselor to an oncologist (P = .02). Fewer women wished to see a primary care physician or gynecologist for pretest education (11%) or posttest counseling (22%). With regard to the counseling process, 82% of women wished to self-refer for genetic counseling, but 63% desired advice and recommendations about whether to be tested. CONCLUSION: When feasible, the optimal approach may be for oncologists to work with genetic counselors to provide pretest education and medical recommendations. Elicitation of patients' preferences may be useful to determine the level of counseling services needed.

Adult↗
PubMed1998

What you don't know can hurt you: adverse psychologic effects in members of BRCA1-linked and BRCA2-linked families who decline genetic testing.

PURPOSE: To identify members of hereditary breast and ovarian cancer families who are at risk for adverse psychologic effects of genetic testing. PATIENTS AND METHODS: A prospective cohort study with baseline (preeducation) assessments of predictor variables (ie, sociodemographic factors, cancer history, and cancer-related stress symptoms) was performed. The primary outcome variable (presence of depressive symptoms) was assessed at baseline and at 1- and 6-month follow-up evaluations. Participants were 327 adult male and female members of BRCA1- and BRCA2-linked hereditary breast and ovarian cancer families, who were identified as carriers, noncarriers, or decliners of genetic testing. RESULTS: The presence of cancer-related stress symptoms at baseline was strongly predictive of the onset of depressive symptoms in family members who were invited but declined testing. Among persons who reported high baseline levels of stress, depression rates in decliners increased from 26% at baseline to 47% at 1-month follow-up; depression rates in noncarriers decreased and in carriers showed no change (odds ratio [OR] for decliners v noncarriers=8.0; 95% confidence interval [CI], 1.9 to 33.5; P=.0004). These significant differences in depression rates were still evident at the 6-month follow-up evaluation (P=.04). CONCLUSION: In BRCA1/2-linked families, persons with high levels of cancer-related stress who decline genetic testing may be at risk for depression. These family members may benefit from education and counseling, even if they ultimately elect not to be tested, and should be monitored for potential adverse effects.

Adolescent↗