Germline variants and family history in caucasian and African-American prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16548-e16548
Author(s):  
Elisa M. Ledet ◽  
Emma M. Ernst ◽  
Joshua Schiff ◽  
Shuwen Lin ◽  
Brian E. Lewis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Genetic Testing ◽  
Family History ◽  
San Francisco ◽  
Testing Methods ◽  
Chi Square ◽  
Genetic Studies ◽  
Pathogenic Variants ◽  
Unknown Significance

e16548 Background: Family history (FH) is a well-documented risk factor for prostate cancer (PCa). Previously, germline pathogenic variants (PVs) have been identified in metastatic PCa. The goal of this study was to fully evaluate cancer FH and assess PVs detected in PCa patients undergoing both detailed FH ascertainment and germline genetic testing. Methods: FHs were collected from 535 PCa pts (Caucasian (Ca) n = 359, African American (AA) n = 85, Other n = 18) at Tulane from 2015-2016. Age at diagnosis, Gleasons, and the presence of metastases at any time were noted for these pts. Chi-square and the Mann-Whitney U tests were performed to identify relationships between clinical parameters and FH. 124 PCa pts including those with both localized and metastatic disease were identified with FHs that met guidelines for genetic testing. Genetic testing was done using a commercially available panel (Invitae, San Francisco, CA) of 25-79 cancer-related genes for mutations/selected exon deletions/duplications. Results: Of the 124 tested pts, 20 pts (16.1%) had ≥ 1 germline PV and 47 pts (37.9%) had ≥ 1 germline variant unknown significance. PVs included: BRCA2 (n = 4), BRCA1 (n = 3), CHEK2 (n = 3), MUTYH (n = 3), ATM (n = 2), TP53 (n = 1), MITF (n = 1), NBN (n = 1), PMS2 (n = 1), and RAD51D (n = 1). No PVs were detected in AA pts (n = 20). 435 of 535 PCa pts (81.3%) had a cancer FH with prostate (37.8%), breast (28.2%), lung (16.4%), colorectal (14.8%), and pancreatic (7.5%) cancer being most common. 281 pts (52.5%) had ≥ 2 relatives with cancer. Pts with PCa FH were more likely to be dx age ≤ 55 (p = 0.017). Median age was younger at dx for pts with PCa FH (p = 0.0005). PCa FH did not alter Gleason or metastatic rate. FH influenced age at dx for Ca men (p = 0.0009, 58 vs. 62.5 and Ca men with PCa FH) were 1.55x more likely to develop metastases (p = 0.035). In AA pts, there were no significant associations between FH, and metastases or age at dx. Conclusions: The most prevalent germline mutations in this cohort were in DNA repair pathway genes. Pts with PCa FH were younger at dx than those without PCa FH. Further studies are needed to understand the co-segregation of PCa with other cancers and genetic studies are needed to clarify the mechanisms of these trends which may differ between Ca and AA men.

Germline pathologic mutations and cancer family history in prostate cancer patients.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 378-378
Author(s):  
Marcus Marie Moses ◽  
Elisa Ledet ◽  
Emma M. Ernst ◽  
Patrick Cotogno ◽  
Joshua Schiff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
San Francisco ◽  
Treatment Options ◽  
Distant Metastases ◽  
Cancer Center ◽  
Chi Square ◽  
Variant Of Uncertain Significance ◽  
Pathogenic Variants ◽  
Uncertain Significance

378 Background: Prostate cancer (PCa) patients (pts) with metastases and/or strong family history (FH) of cancer (Ca) are at higher risk of a germline mutation. The identification of alterations in PCa pts may be important for risk stratification as well as personalizing treatment options. The goal of this study was characterization of FH and pathogenic variants (PV) detected in PCa pts, with both localized and metastatic disease. Methods: 300 PCa pts from Tulane Cancer Center underwent germline testing. 265 Caucasian (C) and 35 African-Americans (AA) were tested and met the NCCN criteria for testing and/or had distant metastases (mets). Germline genetic testing was done via commercial panels (30-80 genes) (Invitae. San Francisco, Ca). PCa pts had extensive FH screening. Clinical annotation included age at diagnosis (dx), race, and presence of mets at any time. Chi square tests were used to compare clinical correlates and PVs. Results: Of the 300 pts tested, 182 pts (60.6%) had mets and 118 (39.4%) did not. 41 pts (13.6%) had ≥ 1 germline pathogenic variant (PV) and 161 pts (53.6%) had ≥ 1 germline variant of uncertain significance (VUS). PVs were detected in BRCA2 (n = 10), MUTYH (n = 8), CHEK2 (n = 6), BRCA1 (n = 4), ATM (n = 4), TP53 (n = 3), PMS2 (n = 2), BLM (n = 2), MITF (n = 2), NBN (n = 1), and RAD51D (n = 1). MUTYH and MITF are not known to be linked to prostate cancer. There was no significant relationships in FH PCa and FH non-PCa in regard to likelihood of a PV (p = .86 and p = .18). Of the 300 pts tested, 136 pts (45.3%) had PCa FH, 131 pts (43.6%) had breast Ca FH, 61 pts (20.3%) had lung Ca FH, 61 pts (20.3%) had colon Ca FH, 37 pts (12.3%) had pancreatic Ca FH, and 32 pts (10.6%) had ovarian Ca FH. 45.6% of C men (n = 121) and 42.8% of AA men (n = 15) had PCa FH. Pts with a non-PCa FH (n = 255) were 1.37 times more likely to develop mets (p = .01168). The median age of dx were 61 for PV pts, 62 for VUS pts, and 61 for negative pts (non-significant). 21/182 pts with mets (11.5%) had a PV; 8/182 (4.4%) pts with mets had a BRCA2 PV. Conclusions: In metastatic patients, FH of prostate cancer alone cannot predict those with PV. The most common Cas observed in these pts were breast, lung, colon and pancreatic. A larger cohort is needed to fully characterize and understand the co-segregation of PCa with other Cas.

Inherited pathologic mutations and family history in patients with prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 185-185
Author(s):  
Shuwen Lin ◽  
Elisa M. Ledet ◽  
Joshua Schiff ◽  
Emma M. Ernst ◽  
Cathryn E. Garvey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Dna Repair ◽  
Genetic Testing ◽  
Family History ◽  
San Francisco ◽  
Metastatic Disease ◽  
Cancer Center ◽  
Pathogenic Variants ◽  
Significant Difference

185 Background: In prostate cancer (PCa), germline pathogenic variants have previously been underestimated. PCa patients (pts) with DNA repair defects have a higher percentage of non-PCa family history (FH) with the most common cancers being derived from the breast, GI tract, ovary, pancreas, lymphoma/leukemia. The goal of this study was to evaluate and characterize pathogenic variants detected in PCa patients undergoing both enhanced FH screening and genetic testing. Methods: In this single-institution study, 535 PCa pts from Tulane Cancer Center over the last year underwent enhanced FH screening, and FH of PCa and other cancers were collected. 124 PCa pts including those with both localized and metastatic disease were identified to have a FH that met NCCN guidelines for genetic testing. Genetic testing was done using a commercially available panel (Invitae, San Francisco, CA) of 25-79 cancer-related genes for mutations and selected exonic deletions/duplications. Results: Of the 124 tested pts, 21 pts (16.9%) had ≥ 1 germline pathogenic variant (PV) and 47 pts (37.9%) had ≥ 1 germline variant of unknown significance (VUS). PVs included: BRCA2 (n = 4), BRCA1 (n = 3), CHEK2 (n = 3), MUTYH (n = 3), ATM (n = 2), TP53 (n = 2), MITF (n = 1), NBN (n = 1), PMS2 (n = 1), and (RAD51D (n = 1). Of the 124 tested pts, 68 pts (54.8%) had PCa FH, 68 (54.8%) had breast cancer FH, 22 (17.7%) had pancreatic cancer FH, 16 (12.9%) had ovarian cancer FH, and 37 (29.8%) had both breast and PCa FH. Between the pt groups (those with PVs, VUSs and negative results), there were no differences in FH rates of PCa, breast, pancreatic, or ovarian cancer. There was no significant difference in the age at diagnosis (dx) between the groups or between pts with PCa FH and those without. The median ages at dx were 65 for PV pts, 60 for VUS pts, and 59 for negative result pts. There were no statistically significant differences in initial Gleason score or metastatic disease status in these three groups (p = 0.35 and p = 0.66). Conclusions: In this dataset, FH cannot discriminate between those with and without inherited PV using a broad panel of genes that include those that alter DNA repair. The implications of these findings are broad. [Table: see text]

Inherited germline mutations in men with prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16564-e16564
Author(s):  
Robert Reid ◽  
Marcie DiGiovanni ◽  
Ryan Bernhisel ◽  
Krystal Brown ◽  
Jennifer Saam ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Hereditary Cancer ◽  
Clinical Information ◽  
Nccn Guidelines ◽  
Commercial Laboratory ◽  
Pathogenic Variants ◽  
Age Of Diagnosis ◽  
History Of

e16564 Background: Recent studies have demonstrated a high prevalence of pathogenic variants (PVs) in genes that confer hereditary cancer risk among men with metastatic prostate cancer (PC); however, PC does not currently receive attention as an indication for genetic testing. We assessed the clinical features of men with PC who received clinical testing as well as the distribution of PVs identified. Methods: A commercial laboratory database was queried to identify men with PC who underwent testing with a multi-gene hereditary cancer panel from September 2013–September 2016. Clinical information was obtained from provider-completed test request forms. Individuals with PC only were evaluated separately from those who had ≥1 additional malignancy. Personal/family history was evaluated relative to the 2013 NCCN guidelines for hereditary breast and ovarian cancer (HBOC) testing. Results: Overall, 700 men with a personal history of PC were identified: 384 (54.9%) with only PC and 316 (45.1%) with PC and ≥1 additional malignancy. The most common additional malignancies were colorectal (115) and breast cancer (105). The median age of diagnosis in men with only PC was 57.5, which is younger than tested men who had an additional malignancy (62) and the SEER data (2009-2013) for all men with PC (66). HBOC testing criteria were met by 75.9% of men, including 44 (6.3%) who met based only on a personal/family history of PC and 202 (28.9%) who met in part due to a personal/family history of PC. PVs were identified in 14.0% of all men: 11.5% of men with PC only and 17.1% of men with PC and a second malignancy (see Table). Conclusions: PC patients selected for genetic testing here were younger than men diagnosed with PC from the general population (SEER), and almost half had a diagnosis of an additional malignancy. They also have a high positive mutation rate across a broad spectrum of genes. [Table: see text]

Inherited germline mutations in men with prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 357-357
Author(s):  
Robert Reid ◽  
Marcie DiGiovanni ◽  
Ryan Bernhisel ◽  
Krystal Brown ◽  
Jennifer Saam ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Hereditary Cancer ◽  
Clinical Information ◽  
Nccn Guidelines ◽  
Pathogenic Variants ◽  
Seer Data ◽  
Age Of Diagnosis ◽  
History Of

357 Background: Recent studies have demonstrated a high prevalence of pathogenic variants (PVs) in genes that confer hereditary cancer risk among men with metastatic prostate cancer (PC); however, PC does not currently receive attention as an indication for genetic testing. We assessed the clinical features of men with PC who received clinical testing as well as the distribution of PVs identified. Methods: Men with PC who underwent testing with a multi-gene hereditary cancer panel (Myriad Genetic Laboratories) from September 2013–September 2017 were included. Clinical information was obtained from provider-completed test request forms. Individuals with PC only were evaluated separately from those who had ≥1 additional malignancy. Personal/family history was evaluated relative to the 2013 NCCN guidelines for hereditary breast and ovarian cancer (HBOC) testing. Results: Overall, 1004 men with a personal history of PC were identified: 606 (60.4%) with only PC and 398 (39.6%) with PC and ≥1 additional malignancy. The most common additional malignancies were breast (136) and colorectal cancer (134). The median age of diagnosis in men with only PC was 59, which is younger than tested men who had an additional malignancy (63) and the SEER data (2009-2013) for all men with PC (66). HBOC testing criteria were met by 78.0% of men, including 68 (6.8%) who met based only on a personal/family history of PC and 330 (32.9%) who met in part due to a personal/family history of PC. PVs were identified in 12.9% of all men: 11.2% of men with PC only and 15.4% of men with PC and a second malignancy (Table). Conclusions: PC patients selected for genetic testing here were younger than men diagnosed with PC from the general population (SEER), and about a third had a diagnosis of an additional malignancy. They also have a high positive mutation rate across a broad spectrum of genes. [Table: see text]

Exploring African American males' attitudes towards genetic testing for prostate cancer risk.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13552-e13552
Author(s):  
Amy Leader ◽  
Thierry Fortune ◽  
Pamela Weddington ◽  
Nicole Crumpler ◽  
Veda N. Giri
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Family History ◽  
Focus Groups ◽  
Cultural Beliefs ◽  
Primary Care Visit ◽  
Health History ◽  
Counseling And Testing

e13552 Background: African American (AA) males have disproportionately high prostate cancer (PCA) incidence and mortality rates compared to men of other races. While genetic testing for PCA is rapidly expanding, AA men represent fewer than 10% of those who undergo genetic counseling and testing. Barriers for AA males may include a lack of awareness or understanding, cultural beliefs, financial and access-to-care limitations, fear of discrimination, and mistrust in the healthcare system. These issues may be exacerbated among low-income, urban AA males. Methods: We conducted two focus groups with AA males who live in a low-resource neighborhood in a major US city to explore their understanding about PCA, challenges in obtaining and discussing family health history, and attitudes towards genetic counseling and testing. Prior to the start of the focus groups, men provided informed consent and completed a brief survey to capture demographic and health history information. Focus groups were moderated by a male member of the community, were audio and video recorded, and transcribed verbatim. Transcripts were analyzed using NVivo 12 to deduce themes within the discussions. Results: Seventeen men participated in one of two focus groups. The mean age was 54 years old (range: 40-66). Only 5 men (30%) were married. Ten men (60%) did not report a family history of PCA, while the remaining 7 reported that their father, grandfather, brother or uncle had PCA. All men had a primary care visit in the past 3 years, but only 13 out of 17 men (76%) reported discussing PCA. Focus group discussions and analyses revealed multiple key themes. Men had limited understanding of the prostate and PCA, with somewhat fatalistic views toward cancer. Family history was recognized as an important risk factor for cancer; talking about family history has become easier and more widely accepted. However, there was mixed reaction to genetic testing: most men were unfamiliar with it but were in favor of learning more, while a few did not see the utility of genetic information. Conclusions: AA men continue to have knowledge deficits about PCA. While there is strong understanding that cancer may be hereditary, there is less awareness about PCA genetic testing. Targeted genetic education and addressing access and cost barriers to genetic testing among AA males is needed to increase uptake of genetic testing and participation in genetic trials.

Evaluation of a Mainstream Model of Genetic Testing for Men With Prostate Cancer

2020 ◽  
pp. OP.20.00399
Author(s):  
Tahlia Scheinberg ◽  
Annabel Goodwin ◽  
Emilia Ip ◽  
Anthony Linton ◽  
Blossom Mak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
San Francisco ◽  
Standard Of Care ◽  
Inherited Cancer ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Counseling And Testing ◽  
Timely Access ◽  
Brca1 Brca2

PURPOSE: To identify the approximately 12% with inherited cancer predisposition, all men with metastatic prostate cancer (mPC) should be offered germline genetic testing. This guides treatment choices and impacts cancer prevention in the family. Limited genetic services globally present a barrier to testing. This study tested a potential solution, “mainstreaming,” where counseling and testing are performed by the patient’s oncologist. PATIENTS AND METHODS: Men with mPC at three Australian sites were offered germline genetic testing at their medical oncology appointment. Panel testing ( ATM, BRCA1, BRCA2, BRIP1, CHEK2, EPCAM, FANCA, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, and TP53) was performed on saliva/blood (Invitae, San Francisco, CA). Primary outcomes were clinician and patient satisfaction. Secondary outcomes included mutation rates and resource allocation. RESULTS: Of 66 men offered testing, 63 (95%) accepted. Four pathogenic variants were identified (two BRCA2, one NBN, and one MSH6). Fifty patients and nine clinicians completed questionnaires. Satisfaction was high. All patients were pleased to have had testing overall, 98% (46 of 47) to have had testing at their usual oncology appointment, and all to receive results from their usual specialist, rather than a separate genetics appointment. A total of 88% (7 of 8) of clinicians felt confident, and all were satisfied with mainstreaming. Mainstreaming was resource efficient, requiring 87% fewer genetic consultations than traditional genetic counseling. CONCLUSION: This study demonstrates that mainstreaming of men with mPC is feasible, resource efficient, and satisfactory for clinicians and patients. Widespread implementation as standard of care would facilitate timely access to genetic testing for men with mPC.

Family history and pathogenic/likely pathogenic germline variants in prostate cancer patients.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 143-143
Author(s):  
Rachel Sabol ◽  
Elisa Marie Ledet ◽  
Ellen Jaeger ◽  
Marcus W. Moses ◽  
Brian E. Lewis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Personal History ◽  
Sample Collection ◽  
First Degree Relatives ◽  
Pathogenic Variants ◽  
Damage Repair ◽  
History Of

143 Background: Recent literature highlights the importance of germline genetic testing in prostate cancer (PCa) patients. Surprisingly, a literature review indicates that family history records are incomplete in published studies. Methods: Prospective and complete family history data were gathered from 496 men in a single institution with a personal history of PCa who underwent germline genetic testing using a panel of at least 79 genes (Invitae testing) from 2016-2020. Comprehensive FH were obtained in all PCa patients in this database and analysis of prevalent FH was assessed at the time of sample collection. Age, race, metastastes at any time, and Gleason score were also ascertained. MUTYH heterozygotes were not considered pathogenic. Results: Pathogenic/likely pathogenic variants (PV/LPVs) were not associated with age at diagnosis, race, or presence of metastasis. Men with Gleason scores 8-10 at time of diagnosis were more likely to have PV/LPV ( P= 0.004). One or more first degree relatives (FDR) with any cancer with was not predictive for germline PV/LPVs for men with PCa ( P= 0.96). Analysis of patients with one or more FDR with breast, prostate, ovarian, or pancreatic cancer revealed that only FDR with breast cancer ( P = 0.028) or ovarian cancer ( P = 0.015) was predictive for PV/LPVs. Though one or more FDR with prostate cancer did not predict a PV/LPV in the overall panel, further analysis indicate that a history of a FDR with PCa was predictive for PV/LPV in a DNA damage repair (DDR) gene ( P= 0.044). Conclusions: In men with a personal history of PCa, germline PV/LPVs were associated with a FDR with breast or ovarian cancer. A FDR with PCa was predictive for PV/LPV in DDR genes. These data emphasize the contribution of FH to germline genetic testing results in a cohort with complete ascertainment of cancer in first degree relatives.

scholarly journals The evolving role of germline genetic testing and management in prostate cancer: Report from the Princess Margaret Cancer Centre International Retreat

2021 ◽  
Vol 15 (12) ◽  
Author(s):  
Roderick Clark ◽  
Miran Kenk ◽  
Kristen McAlpine ◽  
Emily Thain ◽  
Kirsten M. Farncombe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Genetic Risk ◽  
Genetic Disorders ◽  
Future Research ◽  
Policy Action ◽  
Cancer Centre ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
International Experts

Introduction: Prostate cancer is a significant cause of cancer mortality. It has been well-established that certain germline pathogenic variants confer both an increased risk of being diagnosed with prostate cancer and dying of prostate cancer.1 There are exciting developments in both the availability of genetic testing and opportunities for improved treatment of patients. On August 19, 2020, the Princess Margaret Cancer Centre in Toronto, Ontario, hosted a virtual retreat, bringing together international experts in urology, medical oncology, radiation oncology, medical genetics, and translational research, as well as a patient representative. We are pleased to provide this manuscript as a review of those proceedings for Canadian clinicians. Recommendations: We drafted several recommendations for future research and policy action based on this meeting: 1) Need for increased access to funding for germline testing for the common genetic disorders associated with increased risk of prostate cancer. 2) A need for increased research into identifying genetic factors influencing risk stratification, treatment response, and outcomes of prostate cancer within Canadian populations at increased genetic risk for prostate cancer. 3) Need for increased awareness about genetic risk factors among the Canadian public. 4) Need for research on patient perspectives and psychosocial outcomes in individuals identified to be at increased genetic risk of prostate cancer. 5) We support the creation of specialized multidisciplinary clinics that specialize in tailored care for patients at increased genetic risk of prostate cancer.

scholarly journals Germline Pathogenic Variants in 7636 Japanese Patients With Prostate Cancer and 12 366 Controls

2019 ◽  
Vol 112 (4) ◽  
pp. 369-376 ◽  
Author(s):  
Yukihide Momozawa ◽  
Yusuke Iwasaki ◽  
Makoto Hirata ◽  
Xiaoxi Liu ◽  
Yoichiro Kamatani ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Clinical Characteristics ◽  
Statistical Tests ◽  
Japanese Patients ◽  
Pathogenic Variants ◽  
Liver Cancers ◽  
Genetics And Genomics ◽  
Genetic Testing Guidelines ◽  
And Control

AbstractBackgroundGenetic testing has been conducted in patients with prostate cancer (PCa) using multigene panels, but no centralized guidelines for genetic testing exist. To overcome this limitation, we investigated the demographic and clinical characteristics of patients with pathogenic variants.MethodsWe sequenced eight genes associated with hereditary PCa in 7636 unselected Japanese patients with PCa and 12 366 male, cancer-free control individuals. We assigned clinical significance for all 1456 variants using the American College of Medical Genetics and Genomics guidelines and ClinVar. We compared the frequency of carriers bearing pathogenic variants between cases and control participants with calculated PCa risk in each gene and documented the demographic and clinical characteristics of patients bearing pathogenic variants. All statistical tests were two-sided.ResultsWe identified 136 pathogenic variants, and 2.9% of patients and 0.8% of control individuals had a pathogenic variant. Association with PCa risk was statistically significant for variants in BRCA2 (P < .001, odds ratio [OR] = 5.65, 95% confidence interval [CI] = 3.55 to 9.32), HOXB13 (P < .001, OR = 4.73, 95% CI = 2.84 to 8.19), and ATM (P < .001, OR = 2.86, 95% CI = 1.63 to 5.15). We detected recurrent new pathogenic variants such as p.Gly132Glu of HOXB13. Patients with pathogenic variants were 2.0 years younger at diagnosis and more often had smoking and alcohol drinking histories as well as family histories of breast, pancreatic, lung, and liver cancers.ConclusionsThis largest sequencing study of PCa heredity provides additional evidence supporting the latest consensus among clinicians for developing genetic testing guidelines for PCa.

Germline mutations in Brazilian pancreatic carcinoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16749-e16749
Author(s):  
Livia Munhoz Rodrigues ◽  
Simone Maistro ◽  
Maria Lucia Hirata Katayama ◽  
Luiz A.Senna Leite ◽  
Joao Glasberg ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Pancreatic Carcinoma ◽  
Germline Mutations ◽  
Family History Of Cancer ◽  
First Degree Relatives ◽  
Pathogenic Variants ◽  
History Of ◽  
History Of Cancer

e16749 Background: Pancreatic cancer has the prospect of becoming the second leading cause of cancer death by 2030. The NCCN Guidelines recommend genetic testing for all patients with pancreatic cancer, however, the spectrum of germline mutations has not been extensively evaluated because recent studies with genetic testing have explored only a limited number of genes and have focused predominantly on Caucasian populations. Therefore, our objective is to evaluate the frequency and spectrum of germline mutations in unselected patients with pancreatic cancer in a multiethnic population. Methods: Patients from Instituto do Câncer do Estado de São Paulo (Brazil) with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of the family history of cancer. These patients answered a life habits and family history of cancer questionnaire and supplied blood for the Next Generation Sequencing (MiSeq platform) with the TruSight Hereditary Cancer panel (Illumina), which includes 115 cancer predisposing genes. Variant analysis was performed with the VarStation, a Brazilian tool that offers post-sequencing computational support and aid for clinical interpretation. Results: To the present moment, 77 patients were evaluated. The mean age of the patients was 62 years (27-83), among whom, 13% with young age (≤50 years) and 47 women (61%). Thirty-eight patients (49%) reported cases of cancer in first-degree relatives. Regarding risk factors, 41 patients (53%) reported smoking, 19 (25%) alcohol ingestion and 20 (26%) had obesity. Seven out of 77 patients presented pathogenic variants in ATM (n = 2) , CHEK2, FANCM (n = 2) or PALB2 (n = 2) genes. Two of these patients ( CHEK2 and FANCM) had early onset pancreatic cancer (≤45 years), both denied smoking habit and family history of cancer in 1st degree relatives. Two patients, who were ATM mutation carriers, reported 1st or 2nd degree relatives with cancer and are alive after 4 and 8 years of diagnosis. Conclusions: In this unselected group of pancreatic cancer patients, 15% were young, almost half reported first-degree relatives with cancer and 9% were carriers of pathogenic variants in genes related with the homologous recombination DNA repair.

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