Exome sequencing identifies nonsegregating nonsense ATM and PALB2 variants in familial pancreatic cancer.

We sequenced 11 germline exomes from five families with familial pancreatic cancer (FPC). One proband had a germline nonsense variant in ATM with somatic loss of the variant allele. Another proband had a nonsense variant in PALB2 with somatic loss of the variant allele. Both variants were absent in a relative with FPC. These findings question the causal mechanisms of ATM and PALB2 in these families and highlight challenges in identifying the causes of familial cancer syndromes using exome sequencing

Examining intrafamilial communication of colorectal cancer risk status to family members and kin responses to colonoscopy: a qualitative study

Abstract Background First-degree relatives (FDRs) of probands with colorectal cancer (CRC) may be at increased risk of CRC and require colonoscopy. Proband disclosure about this risk and need for colonoscopy is essential for FDRs to take appropriate action. Low colonoscopy rates are reported among FDRs and little is known about the proband disclosure process. A better understanding of the barriers surrounding colonoscopy and disclosure is needed. Methods CRC probands (n = 16) and FDRs (n = 9), recruited from a Canadian CRC Consortium, completed interviews to determine barriers to disclosure and colonoscopy, respectively. Interviews were analyzed using thematic analysis and participants’ motivation to disclose to FDRs or undertake colonoscopy was categorized into Stages of Change (i.e., Precontemplation, Contemplation, Preparation, Action, or Maintenance) using the transtheoretical model. Results 25% of probands had not disclosed to any first-degree kin and were categorized in the Precontemplation or Contemplation Stage of Change. Barriers to disclosure included lack of information, negative expectations about familial reaction, assuming FDRs were aware of risk or already being screened, dysfunctional family dynamics, and cultural barriers. 75% of FDRs were categorized in the Precontemplation or Contemplation Stage of Change. Barriers included negative perceptions about colonoscopy, health-care provider related factors, practical concerns, and lack of information about CRC, risk, and colonoscopy. Conclusions In the absence of barriers such as cost and accessibility, this Canadian sample still reported several challenges to disclosure and colonoscopy adherence. Future research should explore interventions such as motivational interviewing to improve proband disclosure and to increase FDR adherence to colonoscopy

Patient-physician relationships, health self-efficacy, and gynecologic cancer screening among women with Lynch syndrome

Abstract Background Lynch syndrome, a hereditary cancer syndrome, predisposes women to colorectal, endometrial, and ovarian cancer. Current guidelines recommend that women with Lynch syndrome undergo risk-reducing gynecological surgery to reduce their chances of developing endometrial or ovarian cancer. Little is known about how women with Lynch syndrome perceive gynecological cancer screening, or the psychosocial factors associated with screening attitudes and behaviour. Methods This study used a cross-sectional, quantitative design. Using self-report questionnaire data from a sample of women with Lynch syndrome (N = 50) who had not undergone risk-reducing surgery, the current study sought to: 1) describe the gynecological cancer screening behaviours of women with Lynch syndrome, as well participant-reported sources of information about Lynch syndrome; 2) examine the extent to which women believe gynecological cancer screening is effective and provides them with reassurance and; 3) assess to what extent relationships with one’s family physician were associated with gynecological cancer screening, perceptions about screening, and health self-efficacy. Data were analyzed using descriptive statistics and Spearman rank-ordered correlations. Results Data analyses showed that transvaginal ultrasound was the most common screening behaviour (57%) followed by pelvic ultrasound (47%). Only 22% of participants underwent endometrial biopsy. Patient-physician relationships were related to greater health self-efficacy to manage Lynch syndrome and greater perceived effectiveness of gynecological screening. However, health self-efficacy and better patient-physician relationships were not associated with increased engagement in gynecological cancer screening. Conclusions The data suggest that feeling efficacious about managing one’s Lynch syndrome and screening is related to positive interactions and communication with one’s family physician. While this is encouraging, future research should examine educating both family physicians and patients about current guidelines for Lynch syndrome gynecological screening recommendations

Risk assessment and genetic counseling for Lynch syndrome – Practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer

Identifying individuals who have Lynch syndrome involves a complex diagnostic workup that includes taking a detailed family history and a combination of various tests such as immunohistochemistry and/or molecular which may be germline and/or somatic. The National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer have come together to publish this practice resource for the evaluation of Lynch syndrome. The purpose of this practice resource was to provide guidance and a testing algorithm for Lynch syndrome as well as recommendations on when to offer testing. This practice resource does not replace a consultation with a genetics professional. This practice resource includes explanations in support of this and a summary of background data. While this practice resource is not intended to serve as a review of Lynch syndrome, it includes a discussion of background information and cites a number of key publications which should be reviewed for a more in-depth understanding. This practice resource is intended for genetic counselors, geneticists, gastroenterologists, surgeons, medical oncologists, obstetricians and gynecologists, nurses, and other healthcare providers who evaluate patients for Lynch syndrome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172941/1/jgc41546.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172941/2/jgc41546_am.pd