Screening in GI Cancers: The Role of Genetics

2015 ◽  
Vol 33 (16) ◽  
pp. 1721-1728 ◽  
Author(s):  
Elena M. Stoffel

Genetic and epigenetic alterations identified in tumors of different cancer types can provide insights regarding the roles played by different cell signaling pathways in carcinogenesis. Somatic mutation profiles of GI tumors are used to guide choice of chemotherapy and can facilitate identification of individuals whose cancers arise in the setting of genetic predisposition. This review provides a framework for how clinical history, family history of cancer, and tumor genomic phenotype can be used to screen patients with colorectal, gastric, or pancreatic cancer for hereditary cancer syndromes. Early identification of individuals who carry germline mutations can affect clinical care not only for patients with cancer but also for their at-risk relatives.

2006 ◽  
Vol 24 (28) ◽  
pp. 4642-4660 ◽  
Author(s):  
José G. Guillem ◽  
William C. Wood ◽  
Jeffrey F. Moley ◽  
Andrew Berchuck ◽  
Beth Y. Karlan ◽  
...  

Although the etiology of solid cancers is multifactorial, with environmental and genetic factors playing a variable role, a significant portion of the burden of cancer is accounted for by a heritable component. Increasingly, the heritable component of cancer predispositions has been linked to mutations in specific genes, and clinical interventions have been formulated for mutation carriers within affected families. The primary interventions for mutations carriers for highly penetrant syndromes such as multiple endocrine neoplasias, familial adenomatous polyposis, hereditary nonpolyposis colon cancer, and hereditary breast and ovarian cancer syndromes are primarily surgical. For that reason, the American Society of Clinical Oncology (ASCO) and the Society of Surgical Oncology (SSO) have undertaken an educational effort within the oncology community. A joint ASCO/SSO Task Force was charged with presenting an educational symposium on the surgical management of hereditary cancer syndromes at the annual ASCO and SSO meetings, resulting in an educational position article on this topic. Both the content of the symposium and the article were developed as a consensus statement by the Task Force, with the intent of summarizing the current standard of care. This article is divided into four sections addressing breast, colorectal, ovarian and endometrial cancers, and multiple endocrine neoplasia. For each, a brief introduction on the genetics and natural history of the disease is provided, followed by a detailed description of modern surgical approaches, including a description of the clinical and genetic indications and timing of prophylactic surgery, and the efficacy of prophylactic surgery when known. Although a number of recent reviews have addressed the role of genetic testing for cancer susceptibility, including the richly illustrated Cancer Genetics and Cancer Predisposition Testing curriculum by the ASCO Cancer Genetics Working Group (available through http://www.asco.org ), this article focuses on the issues surrounding the why, how, and when of surgical prophylaxis for inherited forms of cancer. This is a complex process, which requires a clear understanding of the natural history of the disease and variance of penetrance, a realistic appreciation of the potential benefit and risk of a risk-reducing procedure in a potentially otherwise healthy individual, the long-term sequelae of such surgical intervention, as well as the individual patient and family's perception of surgical risk and anticipated benefit.


1996 ◽  
Vol 105 (9) ◽  
pp. 694-700 ◽  
Author(s):  
Joseph B. Jacobs ◽  
Barry A. Shpizner ◽  
Eugenie Brunner ◽  
Richard A. Lebowitz ◽  
Roy A. Holliday

Agger nasi cells contribute to nasofrontal duct (NFD) obstruction and chronic frontal sinus disease. To investigate this relationship, we conducted a review of the surgical outcome and computed tomographic imaging in 26 patients with chronic frontal sinusitis. Coronal and sagittal images were used to delineate the anatomic variability and mucosal disease in the NFD and frontal sinus region. Data from coronal and sagittal images were compared. The results were also correlated with the outcome of frontal sinus surgery in patients with a clinical history of chronic frontal sinus disease. Our data suggest that agger nasi cell pneumatization with narrowing of the frontal sinus outflow tract is a significant cause of persistent frontoethmoid pain and chronic frontal sinusitis. Sagittal reformatted images are more capable than coronal images of demonstrating agger nasi cell encroachment on the NFD, as well as NFD mucosal disease. Endoscopic frontal sinusotomy is an effective treatment for chronic frontal sinus disease.


2002 ◽  
Vol 9 (7) ◽  
pp. 607-609 ◽  
Author(s):  
Dimitrios H. Roukos ◽  
Aggelos M. Kappas ◽  
Epameinondas Tsianos

2022 ◽  
Vol 11 ◽  
Author(s):  
Van Thuan Tran ◽  
Sao Trung Nguyen ◽  
Xuan Dung Pham ◽  
Thanh Hai Phan ◽  
Van Chu Nguyen ◽  
...  

BackgroundHereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown.Methods1165 Vietnamese individuals enrolled in genetic testing at our laboratory in 2020. We performed analysis of germline mutations in 17 high- and moderate- penetrance genes associated with HCS by next generation sequencing.ResultsA total of 41 pathogenic variants in 11 genes were detected in 3.2% individuals. The carrier frequency was 4.2% in people with family or personal history of cancer and 2.6% in those without history. The percentage of mutation carriers for hereditary colorectal cancer syndromes was 1.3% and for hereditary breast and ovarian cancer syndrome was 1.6%. BRCA1 and BRCA2 mutations were the most prevalent with the positive rate of 1.3% in the general cohort and 5.1% in breast or ovarian cancer patients. Most of BRCA1 mutations located at the BRCA C-terminus domains and the top recurrent mutation was NM_007294.3:c.5251C>T (p.Arg1751Ter). One novel variant NM_000038.6(APC):c.6665C>A (p.Pro2222His) was found in a breast cancer patient with a strong family history of cancer. A case study of hereditary cancer syndrome was illustrated to highlight the importance of genetic testing.ConclusionThis is the first largest analysis of carrier frequency and mutation spectrum of HCS in Vietnam. The findings demonstrate the clinical significance of multigene panel testing to identify carriers and their at-risk relatives for better cancer surveillance and management strategies.


2015 ◽  
Vol 33 (31) ◽  
pp. 3544-3549 ◽  
Author(s):  
Maureen E. Mork ◽  
Y. Nancy You ◽  
Jun Ying ◽  
Sarah A. Bannon ◽  
Patrick M. Lynch ◽  
...  

Purpose Established guidelines recommend evaluation for hereditary cancer syndromes in patients younger than 50 years diagnosed with colorectal cancer (CRC). This group has been well described in the literature; however, patients diagnosed as adolescents and young adults are not well represented in CRC studies. Here, we define the clinical profile, including the extent of hereditary cancer syndromes and family history of cancer, in patients diagnosed with CRC at age 35 or younger. Patients and Methods We reviewed patients who underwent genetic counseling at our institution during 5 years (2009 to 2013). Data were collected regarding demographics, clinicopathologic information, tumor and genetic testing, and family history. Patients with an identified hereditary cancer syndrome were compared with those without a syndrome. Results Of the 193 patients with evaluable data, 35% had an identifiable hereditary cancer syndrome, including 23 with Lynch syndrome, 22 with mutation-negative Lynch syndrome, 16 with familial adenomatous polyposis, two with constitutional mismatch repair deficiency, two with biallelic MUTYH mutations, and one with Li-Fraumeni syndrome. Patients without a hereditary syndrome more frequently presented with metastatic disease, whereas patients with a syndrome were more likely to present at earlier stages and to have a family history of cancer. Nevertheless, a substantial proportion of the hereditary syndromes (19%) were diagnosed in individuals with no family history of the disease. Conclusion We conclude that patients diagnosed with CRC at age 35 years or younger should receive genetic counseling regardless of their family history and phenotype.


2010 ◽  
Vol 28 (33) ◽  
pp. 4985-4995 ◽  
Author(s):  
Robert G. Maki

Insulin-like growth factors were discovered more than 50 years ago as mediators of growth hormone that effect growth and differentiation of bone and skeletal muscle. Interest of the role of insulin-like growth factors in cancer reached a peak in the 1990s, and then waned until the availability in the past 5 years of monoclonal antibodies and small molecules that block the insulin-like growth factor 1 receptor. In this article, we review the history of insulin-like growth factors and their role in growth, development, organism survival, and in cancer, both epithelial cancers and sarcomas. Recent developments regarding phase I to II clinical trials of such agents are discussed, as well as potential studies to consider in the future, given the lack of efficacy of one such monoclonal antibody in combination with cytotoxic chemotherapy in a first-line study in metastatic non–small-cell lung adenocarcinoma. Greater success with these agents clinically is expected when combining the agents with inhibitors of other cell signaling pathways in which cross-resistance has been observed.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 176-176
Author(s):  
Wilson L Da Costa ◽  
Danielle Guffey ◽  
Raka Bandyo ◽  
Courtney D Wallace ◽  
Carolina Granada ◽  
...  

Abstract Introduction: Cancer-associated thrombosis (CAT) is common among patients with cancer. Risk factors for CAT include type of malignancy, advanced stage, and chemotherapy treatment, but the association of CAT with race and ethnicity remains controversial. Identifying the incidence of CAT among populations susceptible to inequalities in healthcare delivery may help delineate preventive strategies. Methods: We performed a retrospective cohort study at Harris Health System (HHS), a safety-net healthcare system that provides care for underserved minorities and uninsured patients in Houston, TX. We created an integrated database that linked consecutive patients with newly diagnosed invasive cancer with structured electronic health record (EHR) data from 2011-2020 (Figure 1). We followed patients from time of cancer diagnosis to time of first VTE, death, or loss of follow-up. VTE was defined as radiologically confirmed pulmonary embolism (PE), lower extremity deep vein thrombosis (LE-DVT), catheter-related DVT (CR-DVT), or splanchnic vein thrombosis in either inpatient or outpatient setting. We used VTE ICD9/ICD10 billing codes to assess for potential events and confirmed incident, recurrent, and historical events through medical record review. VTE occurring within 30 days prior to cancer diagnosis were considered as CAT at diagnosis. Incidence rates were assessed per 100 person-year (py) within 1 year of diagnosis and stratified by race/ethnicity, cancer type, and cancer stage. Cumulative incidence of VTE was assessed through competing risk method with death as the competing cause. Multivariable Fine-Gray competing risk models were performed to determine the effect of race/ethnicity on the risk of CAT, adjusted for age, sex, body mass index, insurance, cancer site, stage, systemic therapy, recent hospitalization, and prior history of VTE. Results: A total of 9,353 cancer patients were included in the study, where 49.3% were Hispanics, 27.6% were Non-Hispanic Blacks (NHB), 15.5% were Non-Hispanic Whites (NHW), and 7.6% were Asian/Pacific Islander (PI). Most patients (74.7%) were uninsured, 35.8% were obese, 19% had recent hospitalization, and 31.9% had stage IV disease. Overall, 832 developed CAT within 1 year, including 49.4% PE, 28.1% LE-DVT, and 17.1% CR-DVT. The median onset was 69 days (IQR 20-154), but a significant proportion (n=92) was diagnosed in the month before diagnosis. The incidence of CAT was 7.3% at 6 months and 9.6% at 1 year. The overall incidence rate was 11/100 py with a similar trend from 2011 to 2020. Figure 2 shows the variation in incidence rates for different cancer types across stages. The rate increased 2- to 10-fold from stage I to IV, reaching >40/100 py among patients with pancreatic and upper gastrointestinal cancers. Figure 3 shows the impact of race/ethnicity on the incidence of CAT, with 9.3% and 8.4% for NHW and NHB at 6 months, compared to 6.5% and 3.8% for Hispanics and Asian/PI, respectively. In the adjusted multivariable analysis, the risk of CAT remained lower in Hispanics vs. NHW (SHR 0.80 [0.65-0.97]) and Asian/PI vs. NHW (SHR 0.48 [0.32-0.73]). There was no difference in NHB vs. NHW (SHR 1.04 [0.84-1.27]). Other important covariates included history of VTE (SHR 2.29 [1.32-3.97]) and prolonged hospitalization (SHR 1.53 [CI 1.31-1.80]) in addition to staging and cancer types. Compared to no systemic therapy or adjuvant endocrine only, there was a higher incidence of VTE in patients receiving chemotherapy (SHR 1.72 [1.39-2.15]), targeted therapy (SHR 1.58 [1.12-2.23]), immunotherapy (SHR 2.13 [1.30-3.48], but not non-adjuvant endocrine therapy (SHR 0.91 [0.40-2.08]). Conclusion: In the current cancer registry-linked EHR cohort with a high proportion of Hispanics and Blacks from a large safety-net healthcare system in the US, we have observed a high incidence rate of CAT at 11/100 py. This rate is much higher than 3.9-5.8/100 py reported in contemporary cancer registries in Europe (PMID 27709226, 33171494), and likely reflects advanced disease and comorbidity at the time of diagnosis due to delayed care from the lack of health insurance. Despite adjusting for patient-, cancer-, and treatment-specific confounders, we found that Hispanics and Asian/PI had ~20% and ~50% lower rate of VTE, respectively, compared to NHW or NHB. This racial/ethnicity difference should be considered in future risk assessment models for CAT. Figure 1 Figure 1. Disclosures Carrier: Sanofi Aventis: Honoraria, Membership on an entity's Board of Directors or advisory committees; LEO Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aspen: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Honoraria; Servier: Honoraria.


2006 ◽  
Vol 13 (10) ◽  
pp. 1296-1321 ◽  
Author(s):  
José G. Guillem ◽  
William C. Wood ◽  
Jeffrey F. Moley ◽  
Andrew Berchuck ◽  
Beth Y. Karlan ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Swati G. Patel ◽  
Heather Hampel ◽  
Derek Smith ◽  
Dexiang Gao ◽  
Myles Cockburn ◽  
...  

Abstract Background 16–25% of colorectal cancers (CRCs) diagnosed under age 50 are associated with hereditary cancer syndromes. Advanced adenomas are considered precursors to CRC. Although polyp removal prevents cancer, polypectomy does not change underlying genetic risk. Patients with isolated advanced polyps do not currently qualify for genetic testing unless they have a personal or family history of cancer. Aim Describe the prevalence of hereditary cancer syndromes among patients with advanced colorectal polyps. Methods We performed a single center retrospective review from 2015 to 2019 of patients who underwent germline genetic testing with indication for testing listed as colorectal polyp. We excluded patients with a personal history of CRC and those with ≥10 cumulative polyps. We collected patient demographics, polyp characteristics, family history data and genetic testing results from the medical record. Discrete variables were reported as frequency and percentages and continuous variables reported as mean with range. Results A total of 42 patients underwent genetic testing due to a personal history of advanced adenoma. 17% of patients met current genetic testing criteria. All patients underwent multi-gene panel testing. Two patients (4.8%) had a germline pathogenic mutation (one in MLH1 and one in CHEK2). The patient with an MLH1 mutation met current criteria for genetic testing (PREMM5 score 5.8), however the patient with the CHEK2 mutation did not. Both mutation carriers had a personal history of synchronous or metachronous advanced adenomas. 38% had a variant of uncertain significance. Conclusions 5% of patients with advanced adenomas in our retrospective series had a pathogenic germline mutation in a cancer predisposition gene. Though the patient with a pathogenic mutation in MLH1 met current clinical criteria for genetic testing, this was not recognized prior to referral; he was referred based on a personal history of advanced adenoma. Advanced polyps may be a red flag to identify patients who are at risk for hereditary cancer syndromes.


Reports ◽  
2021 ◽  
Vol 4 (4) ◽  
pp. 39
Author(s):  
Manuela Colosimo ◽  
Maria Lucia Citraro ◽  
Cinzia Donato ◽  
Filippo Luciani ◽  
Luca Gallelli ◽  
...  

Ralstonia pickettii is an opportunistic bacillus found in Pseudomonas species, with the ability to induce systemic infections. We report the case of a 69-year-old man, with a clinical history of myeloma, Type IIdiabetes, renal failure (grade IV), and colon cancer, that developed a severe bacterial infection, with acute asthenia and a fever, that appeared at the end of dialysis. Using theMALDI-TOF technology, the bacillus Ralstonia pickettii was identified, and an antimicrobial treatment was quickly started with a rapid microbiological remission.


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