Colorectal Cancer in the Family: Psychosocial Distress and Social Issues in the Years Following Genetic Counselling

<p>Abstract</p> <p>Background</p> <p>This study examined: (1) levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC); (2) associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3) the impact of genetic counselling on family relationships, and (4) social consequences of genetic counselling.</p> <p>Methods</p> <p>In this cross-sectional study, individuals who had received genetic counselling for HNPCC during 1986–1998 completed a self-report questionnaire by mail.</p> <p>Results</p> <p>116 individuals (81% response rate) completed the questionnaire, on average 4 years after the last counselling session. Of all respondents, 6% had clinically significant levels of cancer-specific distress (Impact of Event Scale, IES). Having had contact with a professional psychosocial worker for cancer risk in the past 10 years was significantly associated with higher levels of current cancer specific distress. Only a minority of the counselees reported any adverse effects of genetic counselling on: communication about genetic counselling with their children (9%), family relationships (5%), obtaining life insurance (8%), choice or change of jobs (2%), and obtaining a mortgage (2%).</p> <p>Conclusion</p> <p>On average, four years after genetic counselling for HNPCC, only a small minority of counselled individuals reports clinically significant levels of distress, or significant family or social problems.</p

International cancer of the pancreas screening (CAPS) consortium summit on the management of patients with increased risk for familial pancreatic cancer

Background Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. Objective To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. Methods A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥75% agreed or disagreed. Results There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz–Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screeni

A novel pathogenic MLH1 missense mutation, c.112A > C, p.Asn38His, in six families with Lynch syndrome

<p>Abstract</p> <p>Background</p> <p>An unclassified variant (UV) in exon 1 of the <it>MLH1 </it>gene, c.112A > C, p.Asn38His, was found in six families who meet diagnostic criteria for Lynch syndrome. The pathogenicity of this variant was unknown. We aim to elucidate the pathogenicity of this <it>MLH1 </it>variant in order to counsel these families adequately and to enable predictive testing in healthy at-risk relatives.</p> <p>Methods</p> <p>We studied clinical data, microsatellite instability and immunohistochemical staining of MMR proteins, and performed genealogy, haplotype analysis and DNA testing of control samples.</p> <p>Results</p> <p>The UV showed co-segregation with the disease in all families. All investigated tumors showed a microsatellite instable pattern. Immunohistochemical data were variable among tested tumors. Three families had a common ancestor and all families originated from the same geographical area in The Netherlands. Haplotype analysis showed a common haplotype in all six families.</p> <p>Conclusions</p> <p>We conclude that the <it>MLH1 </it>variant is a pathogenic mutation and genealogy and haplotype analysis results strongly suggest that it is a Dutch founder mutation. Our findings imply that predictive testing can be offered to healthy family members. The immunohistochemical data of MMR protein expression show that interpreting these results in case of a missense mutation should be done with caution.</p

Body weight and risk of breast cancer in BRCA1/2 mutation carriers

Contains fulltext : 95679.pdf (publisher's version ) (Closed access)Obesity is an established risk factor for postmenopausal breast cancer in the general population. However, it is still unclear whether this association also exists in BRCA1/2 mutation carriers. We investigated the association between self-reported anthropometric measures and breast cancer risk in a nationwide retrospective cohort study, including 719 BRCA1/2 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. All time-varying Cox proportional hazards analyses were stratified by menopausal status. For premenopausal breast cancer, no statistically significant associations were observed for any of the anthropometric measures. The association between body mass index (BMI) at age 18 and premenopausal breast cancer risk suggested a trend of decreasing risk with increasing BMI (HR(22.50-24.99 vs. 18.50-22.49) = 0.83, 95% CI = 0.47-1.44 and HR(>/= 25.00 vs. 18.50-22.49) = 0.41, 95% CI = 0.13-1.27). For postmenopausal breast cancer, being 1.67 m and taller increased the risk 1.7-fold (HR = 1.67, 95% CI = 1.01-2.74) when compared to a height /= 72 kg increased the risk of postmenopausal breast cancer 2.1-fold (95% CI = 1.23-3.59). A current BMI of >/= 25.0 kg/m(2), an adult weight gain of 5 kg or more, and a relative adult weight gain of 20% or more were all non-significantly associated with a 50-60% increased risk of postmenopausal breast cancer [HR = 1.46 (0.86-2.51), HR = 1.56 (95% CI = 0.85-2.87), and HR = 1.60 (95% CI = 0.97-2.63), respectively], when compared with having a healthy or stable weight. No associations for body weight or BMI at age 18 were observed. In conclusion, menopausal status seemed to modify the association between body weight and breast cancer risk among BRCA1/2 carriers. We observed no clear association between body weight and premenopausal breast cancer, while overweight and weight gain increased postmenopausal breast cancer risk. Carriers may reduce their risk of postmenopausal breast cancer by maintaining a healthy body weight throughout life

Feasibility of a pancreatic cancer surveillance program from a psychological point of view

: The success of any surveillance program depends not solely on its technological aspects but also on the commitment of participants to adhere to follow-up investigations, which is influenced by the psychological impact of surveillance. This study investigates the psychological impact of participating in a pancreatic cancer surveillance program. : High-risk individuals participating in an endoscopic ultrasonography-magnetic resonance imaging-based pancreatic cancer surveillance program received a questionnaire assessing experiences with endoscopic ultrasonography and magnetic resonance imaging, reasons to participate, psychological distress, and benefits and barriers of surveillance. High-risk individuals were individuals with a strong family history of pancreatic cancer or carriers of pancreatic cancer-prone gene mutations. : Sixty-nine participants (85%) completed the questionnaire. Surveillance was reported as "very to extremely uncomfortable" by 15% for magnetic resonance imaging and 14% for endoscopic ultrasonography. Most reported reason to participate was that pancreatic cancer might be detected in a curable stage. Abnormalities were detected in 27 respondents, resulting in surgical resection in one individual and a shorter follow-up interval in five individuals. Surveillance outcomes did not influence cancer worries. Overall, 29% was "often" or "almost always" concerned about developing cancer. Six respondents (9%) had clinical levels of depression and/or anxiety. According to 88% of respondents, advantages of surveillance outweighed disadvantages. : Although endoscopic ultrasonography is more invasive than magnetic resonance imaging, endoscopic ultrasonography was not perceived as more burdensome. Despite one third of respondents worrying frequently about cancer, this was not related to the surveillance outcomes. Anxiety and depression levels were comparable with the general population norms. Advantages of participation outweighed disadvantages according to the majority of respondents. From a psychological point of view, pancreatic cancer surveillance in high-risk individuals is feasible and justifie