Risk Of Gastrointestinal Tumors Research Articles

Association between human blood metabolome and the risk of gastrointestinal tumors.

The prevalence of gastrointestinal tumors continues to be significant. To uncover promising therapeutic targets for these tumors, we rigorously executed a Mendelian randomization (MR) study to comprehensively screen the blood metabolomes for potential causal mediators of five frequently encountered gastrointestinal tumors (Liver Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer and Pancreatic Cancer). We selected a comprehensive set of 137 distinct blood metabolites derived from three large-scale genome-wide association studies (GWASs) involving a total of 147827 participants of European ancestry. The gastrointestinal tumors-related data were obtained from a GWAS conducted within the Finnish study. Through meticulous MR analyses, we thoroughly assessed the associations between blood metabolites and gastrointestinal tumors. Additionally, a phenome-wide MR (Phe-MR) analysis was employed to investigate the potential on-target side effects of metabolite interventions. We have identified 1 blood metabolites, namely isovalerylcarnitine (ORlog10: 1.01; 95%CI, 1.01-1.02; P = 1.81×10-7), as the potential causal mediators for liver cancer. However, no potential pathogenic mediators were detected for the other four tumors. The current systematic MR analysis elucidated the potential role of isovalerylcarnitine as a causal mediator in the development of liver cancer. Leveraging the power of Phe-MR study facilitated the identification of potential adverse effects associated with drug targets for liver cancer prevention. Considering the weighing of pros and cons, isovalerylcarnitine emerges as a promising candidate for targeted drug interventions in the realm of liver cancer prevention.

P84 Peutz-Jeghers syndrome-cutaneous manifestations-case report

Peutz-Jeghers syndrome is an autosomal dominant disorder characterized by extensive hamartomatous polyps and carcinomas throughout the gastrointestinal tract, mainly the small intestine. Intussusception with resultant bleeding and abdominal pain is the most common gastrointestinal manifestation. The characteristic cutaneous features of this condition are the freckle-like pigmented macules that occur on the lips, nose, buccal mucosa, fingertips, and under the nails. The risk of gastrointestinal tumors is higher than in the general population, although most of these lesions do not evolve from the polyps, which are histologically benign. There appears to be an increased risk of pancreatic cancer, breast cancer, and reproductive neoplasms, including tumors of the cervix, ovary, and testis. Aim of this study is to present a case report of a 55 years man with Peutz-Jeghers syndrome.

Abstract B7: Use of risk assessment services and predictive genetic testing (PGT) for hereditary gastrointestinal (GI) cancers: How do men and women differ?

Abstract Background: Uptake of risk assessment and PGT for hereditary GI cancer risk has lagged far behind that of the hereditary breast-ovarian cancer syndrome and BRCA1/2, despite the parallel clinical availability of genetic services for hereditary GI cancers, the proportion of patients with incident colorectal cancers who demonstrate familial risk (∼ 1 in 3), and the prevalence of Lynch syndrome associated mismatch repair gene mutations among incident colorectal cancers (∼ 3–5%). The bulk of data on perceptions of PGT have focused on women considering BRCA1/2 testing for personal and/or familial risk estimation. Studies in men are less plentiful, and have often focused on men's opinions about PGT for prostate cancer risk, although clinical PGT for hereditary prostate cancer is not currently available. Individuals enrolled in a high-risk GI cancer registry represent a unique population in which important differences in perceptions of PGT between men and women may be directly examined to shed light on barriers to risk assessment and PGT, and cancer prevention services in general, that may differ by gender. Methods: The GI Tumor Risk Assessment Program (GI-TRAP) registry at Fox Chase Cancer Center enrolls individuals at increased risk for GI cancers because of a suggestive personal or family history. At enrollment and prior to risk education and counseling, participants are asked to complete a detailed personal and family history and a questionnaire examining screening practices and psychosocial aspects of hereditary cancer risk. The GI-TRAP registry currently contains information collected from members of 269 families. Results: Women (n=293) participants outnumbered men (n=105) almost 3 to 1, were younger (47.0 vs 50.8 yrs)(p=0.01), and were less likely to work full-time (39.9% vs 59.0%)(p<0.001). The most common reasons for wanting testing in both groups were to guide screening (91.4% men, 95.7% women)(p=0.11) and learn children's risks (75.8% men, 83.7% women)(p=0.09). Women were more likely to want testing as a global means to “take better care of myself” (p=0.004), and were more concerned about personal (p=0.05) and family (p=0.04) emotional reactions to testing results, as well as the possible impact of testing on health insurance (p=0.06). Men were more willing to pay for genetic testing (“I plan to get genetic testing even if I have to pay”)(p=0.02) and were more willing to pay larger sums for testing (“I would pay equal to or over $1000 for genetic testing”)(p=0.04). Conclusions: Compared to women, overall fewer men obtain available risk assessment services for hereditary GI cancers. Men seek risk assessment for similar reasons to women, but express lower concern for out-of-pocket costs or adverse personal and familial emotional reactions to testing results. Efforts to make cancer risk assessment services more visible and available to men and working individuals (e.g., expanded clinical hours, on-site education/counseling at places of employment, health clubs, etc) may help to increase the identification of high-risk individuals who would benefit from tailored GI prevention education, genetic counseling, and PGT. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B7.

Diverse cancer prevention needs in a population seeking risk assessment for gastrointestinal (GI) cancers

1539 Background: Demand for hereditary cancer risk assessment has increased dramatically in the past decade. However, the population seeking risk assessment for GI cancers is heterogeneous, requiring primary (PP), secondary (SP), and tertiary (TP) prevention strategies. In an effort to improve targeting of prevention resources, we examined clinical cancer prevention needs as well as 1) estimates of personal risk, 2) risk beliefs 3) interest in genetic testing (GT) among individuals seeking GI risk evaluation. Methods: The Gastrointestinal Tumor Risk Assessment Program (GI-TRAP) offers risk assessment to persons seeking evaluation for a risk of a GI or related cancer. Following informed consent, participants complete a health history questionnaire prior to counseling, education, and genetic services. Results: In total, 398 individuals from 278 families were evaluated (1999–2008)( Table 1 ). Moderate-to-high risk persons with SP needs (i.e. intensive screening, chemoprevention, and genetic testing), dominated the population (281/398, 70.6%), mainly due to significant family history (FHx) of GI-related cancer (236/281, 84.0%) and/or personal history (PHx) of colorectal polyps (128/281, 45.6%). Individuals at high-risk due to a PHx of cancer were infrequent (68/398, 17.1%); here, TP needs focused on GT were common, as interest was highest in this group (p<0.01). A low-risk group (49/411, 11.9%) with minimal PHx or FHx, had mainly PP needs (i.e. risk factor management, education related to appropriate screening). Nonetheless, prior to counseling, the magnitude of personal estimated risk in this group paralleled that of the higher risk groups. Conclusions: Perceived cancer risks and beliefs may not reflect true prevention needs. Risk stratification strategies are critical for targeting education, risk counseling, and/or GT resources while maximizing current prevention goals. [Table: see text] No significant financial relationships to disclose.