ATM mutation carriers and family history of pancreatic cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1529-1529
Author(s):  
Jeannie Klavanian ◽  
Dana Zakalik ◽  
Anish S Konde ◽  
Tara Rangarajan
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Gene Mutations ◽  
Close Relative ◽  
Degree Relative ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Age Of Diagnosis ◽  
History Of ◽  
Atm Gene

1529 Background: Multigene panel testing (MGT) is commonly utilized in patients with a personal or family history of cancer. One of the more common gene mutations identified is in the ATM gene, associated with a moderately increased risk of breast and other cancers. There are reports of an association with pancreatic cancer, however the exact risks are unclear. The aim of this study is to describe the family history of pancreatic cancer in a cohort of ATM mutation carriers, and to evaluate possible genotype/phenotype correlation. Methods: Patients who underwent MGT, between ‘13 and ‘19, and tested positive for a pathogenic/likely pathogenic ATM mutation were included in this study. Family history, with a focus on pancreatic cancer, and genetic testing results were analyzed. Results: A total of 114 patients were identified to carry an ATM mutation. Twenty-two (19.3%) individuals had a family history of pancreatic cancer in a close relative, and of those, 13 (11.4%) had an affected first degree relative, and 11 (9.6%) had an affected second degree relative. Among the families with pancreatic cancer, 20 close relatives had a personal history of pancreatic cancer, with the youngest diagnosed at age 40, the oldest diagnosed at age 91, and a mean age of diagnosis of 66.5 years. Thirteen unique variants were identified: 4 splice site, 3 missense, 3 frameshift, 1 nonsense, and 1 silent. Two families had the known high-penetrance ATM mutation, c.7271T > C (p.V2424G). Conclusions: This study describes the association of pancreatic cancer in individuals found to carry pathogenic ATM mutations. A significant proportion (19.3%) of patients had a family history of pancreatic cancer in a close relative, diagnosed as young as age 40. The mean age of diagnosis was slightly younger than the average age in the general population (age 70). As pancreatic cancer screening continues to improve, this information will be an important component to help guide cancer risk assessment and future screening recommendations for ATM mutation carriers. Additional larger studies are needed to further characterize pancreatic cancer risks in patients with ATM gene mutations.

scholarly journals Family History of Cancer and Tobacco Exposure in Index Cases of Pancreatic Ductal Adenocarcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
R. Lochan ◽  
A. K. Daly ◽  
H. L. Reeves ◽  
R. M. Charnley
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Pancreatic Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Tobacco Exposure ◽  
Degree Relative ◽  
Family History Questionnaire ◽  
Increased Risk ◽  
History Of ◽  
History Of Cancer

Aim. To examine interaction between history of cancer in first-degree relatives and tobacco smoking in index patients of pancreatic adenocarcinoma.Methods. We carried out a case-control involving 113 patients with pancreatic adenocarcinoma and 110 controls over a 12-month period at the Freeman Hospital, Newcastle upon Tyne, UK. They were all administered a detailed tobacco exposure questionnaire and a family history questionnaire. We calculated cumulative tobacco exposure and risk for pancreas cancer.Results. Both smokers (OR 3.01 (95% CI: 1.73 to 5.24)) and those with a family history of malignancy (OR 1.98 (95% CI: 1.15–3.38)) were more likely to develop pancreatic cancer. Having more than one first-degree relative with cancer did not significantly further increase the risk of pancreatic cancer. Amongst pancreatic cancer cases, cumulative tobacco exposure was significantly decreased () in the group of smokers (current and ex-smokers) who had a family history of malignancy [mean (SD): 30.00 (24.77) pack-years versus 44.69 (28.47) pack-years with no such history].Conclusions. Individuals with a family history of malignancy are at an increased risk of pancreatic cancer. Furthermore, individuals with a family history of malignancy and who smoke appear to require a lesser degree of tobacco exposure for the development of pancreatic cancer.

Does a family history of adenomatous colon polyp(s) in a first-degree relative pose an increased risk of developing colon cancer?

2018 ◽  
Vol 21 (4) ◽  
pp. E8
Author(s):  
Ernestine Clements ◽  
Lena Gamble ◽  
Nathan Way ◽  
Lacy Smith ◽  
John B. Waits
Keyword(s):  
Colon Cancer ◽  
Family History ◽  
Colon Polyp ◽  
Degree Relative ◽  
Increased Risk ◽  
History Of ◽  
Relative Pose

Frequency of BRCA1 5382insC mutations in Russian non-selected pancreatic cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15165-e15165
Author(s):  
Alexey Kashintsev
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Founder Mutation ◽  
Brca1 Mutation ◽  
Parp Inhibitors ◽  
Mutation Carriers ◽  
Brca 1 ◽  
History Of ◽  
Associated Tumors

e15165 Background: Pancreatic cancer (PC) is known to be associated with BRCA2 mutations, while the role of BRCA1 in the increase of PC risk is less evident. BRCA1/2-driven tumors, including pancreatic cancer, are sensitive to platinating agents and PARP inhibitors. Epidemiology of BRCA1 mutations in Russia is characterized by a pronounced founder effect, with the allele BRCA1 5382insC being detected in 70-90% of all BRCA1 mutation carriers. Methods: 237 patients with consecutive patients with pancreatic cancer were by questionnaires, and 149 have provided their normal DNA to the study and underwent genotyping for BRCA 1 5382insC mutations. Results: Among all the patients in 105/237 (44.3%) patients reported first-degree relatives with various types of cancer, including 11/237 (4.6%) cases of pancreatic cancer. 2/149 genotyped patients carried BRCA1 5382insC allele. Both mutation carriers had first-degree family history of breast cancer. Conclusions: Given the simplicity of founder mutation detection, BRCA1 5382insC allele deserves to be tested in Slavic pancreatic cancer, especially in those reporting family history of BRCA1-associated tumors.

Risk for death from prostate cancer predicted from complete family history of lethal prostate cancer (LPC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 175-175
Author(s):  
Frederick S. Albright ◽  
Neeraj Agarwal ◽  
William Thomas Lowrance ◽  
Robert A Stephenson ◽  
Anitha Alex ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Registry ◽  
Death Certificate ◽  
Population Data ◽  
Expected Number ◽  
Degree Relative ◽  
Increased Risk ◽  
History Of ◽  
Lethal Prostate Cancer

175 Background: There are few published reports of relative risk (RR) for LPC based on family history of prostate cancer (PC) lethality. This study provides LPC RR using complete LPC family history data obtained from a statewide Cancer Registry linked to a genealogy database. Methods: The Utah Population Data Base (UPDB), which includes a statewide SEER cancer registry, includes 1,192,768 individuals with at least 12 of their 14 immediate ancestors. All males (probands) with specific LPC constellations were identified in the UPDB, and the observed number of LPC cases among these probands was compared to the expected number of LPC cases using internal cohort-specific rates from Utah death certificates including all deceased males with no 1st, 2nd, or 3rd degree relatives with LPC. LPC Family history was estimated for 1st degree to 3rd degree relatives for: number of LPC relatives affected, paternal versus maternal family history, and age at first PC diagnosis. Results: 3,921 individuals in UPDB were diagnosed with histologically confirmed PC, and had a Utah death certificate indicating PC as a cause of death and were designated LPC. The RR for LPC was significantly elevated with each additional first-degree relative (FDR) with LPC; even in the absence of FDR family history of LPC, significantly increased risk for LPC was observed in the presence of at least 1 LPC affected second degree relative (SDR). In the absence of positive FDR and SDR family history for LPC, there was still increased risk for LPC for males with 2 or more third degree relatives with LPC. Early age PC diagnosis in the LPC relative did not appear to affect LPC RR. Higher risks of LPC were associated with the maternal compared to the paternal lineages. Conclusions: Examination of lethal prostate cancer family history (in FDRs through TDRs) may be useful in identifying the cohort of men with prostate cancer most at risk for death from prostate cancer. Focused screening and treatment of this cohort holds potential to decrease the rates of undertreatment of lethal disease while avoiding over diagnosis and overtreatment in inconsequential disease.

Exploring a possible relationship of germline CDKN2A mutations with breast cancer in a multigene panel cohort.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23218-e23218 ◽  
Author(s):  
Darling J Horcasitas ◽  
Holly LaDuca ◽  
Amal Yussuf ◽  
Ginger Chisholm ◽  
Jonah R Chavez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pancreatic Cancer ◽  
Family History ◽  
Breast Cancer Diagnosis ◽  
Case Control ◽  
Control Analysis ◽  
Cdkn2a Mutation ◽  
Mutation Carriers ◽  
History Of ◽  
Relationship Of

e23218 Background: Germline mutations in CDKN2A have been known to increase the risk of melanoma and pancreatic cancer compared to the general population. With the advent of multi-gene panels, individuals who may not have melanoma or pancreatic cancer are undergoing CDKN2A analysis. Previous studies in homogenous populations have suggested that breast cancer risks may also be increased in CDKN2A. This study aims to further evaluate a possible relationship of CDKN2A mutations with breast cancer through a series of case-control comparisons. Methods: Clinical histories and molecular results were retrospectively reviewed for patients undergoing CDKN2A analysis as part of two diagnostic pan-cancer panels at a single laboratory to ascertain CDKN2A mutation carriers (n = 104) and patients negative for all genes analyzed (n = 20,280). Patients with a personal and/or family history (1st and 2nd degree relatives) of pancreatic cancer and/or melanoma were excluded from case-control analysis. Results: The majority of CDKN2A mutation carriers (82.6%, n = 86/104) had a personal history of cancer documented on the test requisition form. The most common cancers were breast (n = 38, 52.8%), melanoma (n = 37, 43.0%) and pancreatic (n = 6, 7.1%). The average age of breast cancer diagnosis in this cohort was 49.3 years (range 25-84). Family history of breast, melanoma, and/or pancreatic cancer was reported for 54.9%, 46.1%, and 34.3% of CDKN2A mutation carriers, respectively. Females with breast cancer were not more likely to test positive for a CDKN2A mutation than females with cancer other than breast (OR = 0.84, p = 0.79) or unaffected females (OR = 1.02, p = 1). Conclusions: Although CDKN2A mutations were not significantly associated with breast cancer in this cohort, these findings do not necessarily rule out an association of CDKN2A mutations with breast cancer, particularly if risks are moderate or if genotype-phenotype correlations exist. Additional studies involving breast cancer cases unselected for age and family history and/or longitudinal studies of CDKN2A carriers are needed to better understand the relationship between CDKN2A and breast cancer risk.

scholarly journals Impact of Changing Guidelines on Genetic Testing and Surveillance Recommendations in a Contemporary Cohort of Breast Cancer Survivors with Family History of Pancreatic Cancer

2021 ◽  
Author(s):  
Annie Wang ◽  
Jessica N. Everett ◽  
Jennifer Chun ◽  
Cindy Cen ◽  
Diane M. Simeone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Cancer Survivors ◽  
Breast Cancer Survivors ◽  
Degree Relative ◽  
Genetic Risk Assessment ◽  
Changing Practice ◽  
History Of

Abstract Background: Changing practice guidelines and recommendations have important implications for cancer survivors. This study investigated genetic testing patterns and outcomes and reported family history of pancreatic cancer (FHPC) in a large registry population of breast cancer (BC) patients. Methods: Variables including clinical and demographic characteristics, FHPC in a first or second-degree relative, and genetic testing outcomes were analyzed for BC patients diagnosed between 2010-2018 in the NYU Langone Health Breast Cancer Database. Results: Among 3334 BC patients, 232 (7%) had a positive FHPC. BC patients with FHPC were 1.68 times more likely to have undergone genetic testing (p<0.001), but 33% had testing for BRCA1/2 only and 44% had no genetic testing. Pathogenic germline variants (PGV) were identified in 15/129 (11.6%) BC patients with FHPC, and in 145/1315 (11.0%) BC patients without FHPC. Across both groups, updates in genetic testing criteria and recommendations could impact up to 80% of this cohort. Conclusions: Within a contemporary cohort of BC patients, 7% had a positive FHPC. The majority of these patients (56%) had no genetic testing, or incomplete testing by current standards, suggesting under-diagnosis of PC risk. This study supports recommendations for survivorship care that incorporate ongoing genetic risk assessment and counseling.

Risk of breast cancer among Japanese women with a positive family history.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 191-191
Author(s):  
J. Suzuki ◽  
T. Hojo ◽  
K. Jimbo ◽  
S. Asaga ◽  
T. Kinoshita
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Positive Family History ◽  
Gene Mutations ◽  
Contralateral Breast ◽  
Brca1 And Brca2 ◽  
Degree Relative ◽  
Increased Risk ◽  
Significant Difference ◽  
Second Degree

191 Background: Most breast cancer cases are sporadic, rather than associated with inherited gene mutations, such as BRCA1 and BRCA2. However, women with a family history of breast cancer are at increased risk of developing breast cancer compared to those women without any family history, even if they lack these gene mutations. Methods: We analyzed 10892 patients including bilateral breast cancer cases (total of 11398 breast cancers) who underwent surgery at our hospital between 1962 and 2009. We excluded 295 cases whose family history data were not available. Clinical and pathological differences between following patient groups were tested; 9528 patients or 9955 cancers (88%) with negative family history (FH-), 896 patients or 951 cancers (8%) who had at least one first-degree relative with breast cancer (1FH+), 468 patients or 492 cancers (4%) who had second-degree relative with breast cancer (2FH+), and 1364 patients or 1443 cancers (12%) with family history regardless of first- or second-degree relative (FH+). Significance was established at a p-value of < 0.05. Results: Among the family members, sisters were more likely to have treated for breast cancer (38% in FH+ group), followed by mothers (27%), aunts (26%), grandmothers (7%), and daughters (2%). The incidence of developing contralateral breast cancer was significantly higher in 1FH+ group, compared to patients in FH- and 2FH+ groups. No other factors showed any significant difference, including the incidence of cancer in other organs, pathological characteristics, and age of onset, although BRCA1 and BRCA2 mutation may be associated with increased risk of developing breast cancer at younger age. Outcome studies with available data did not show any significant difference in overall survival between FH+ and FH- patients. Conclusions: A Japanese woman with a positive family history has a higher risk of developing breast cancer than women without any close relatives with breast cancer, similar to the results reported in Western countries where prevalence of breast cancer is higher. Regular checkup of contralateral breast is important for those patients whose first-degree relatives have also been diagnosed with breast cancer.

Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion

2019 ◽  
Vol 37 (2) ◽  
pp. 153-164 ◽  
Author(s):  
Elena M. Stoffel ◽  
Shannon E. McKernin ◽  
Randall Brand ◽  
Marcia Canto ◽  
Michael Goggins ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Pancreatic Adenocarcinoma ◽  
Health Care Providers ◽  
Expert Panel ◽  
Familial Pancreatic Cancer ◽  
Care Providers ◽  
Increased Risk ◽  
History Of

Purpose An ASCO provisional clinical opinion (PCO) offers timely clinical direction to ASCO’s membership and other health care providers. This PCO addresses identification and management of patients and family members with possible predisposition to pancreatic adenocarcinoma. Methods ASCO convened an Expert Panel and conducted a systematic review of the literature published from January 1998 to June 2018. Results of the databases searched were supplemented with hand searching of the bibliographies of systematic reviews and selected seminal articles and contributions from Expert Panel members’ curated files. Provisional Clinical Opinion All patients diagnosed with pancreatic adenocarcinoma should undergo assessment of risk for hereditary syndromes known to be associated with an increased risk for pancreatic adenocarcinoma. Assessment of risk should include a comprehensive review of family history of cancer. Individuals with a family history of pancreatic cancer affecting two first-degree relatives meet criteria for familial pancreatic cancer (FPC). Individuals (cancer affected or unaffected) with a family history of pancreatic cancer meeting criteria for FPC, those with three or more diagnoses of pancreatic cancer in same side of the family, and individuals meeting criteria for other genetic syndromes associated with increased risk for pancreatic cancer have an increased risk for pancreatic cancer and are candidates for genetic testing. Germline genetic testing for cancer susceptibility may be discussed with individuals diagnosed with pancreatic cancer, even if family history is unremarkable. Benefits and limitations of pancreatic cancer screening should be discussed with individuals whose family history meets criteria for FPC and/or genetic susceptibility to pancreatic cancer. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Differences in the Distribution of Cytogenetic Subtypes Between Multiple Myeloma Patients with and without a History of Familial MGUS and Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4000-4000
Author(s):  
Alexandra Greenberg ◽  
Margot Cousin ◽  
Celine M Vachon ◽  
Dirk Larson ◽  
Colin L. Colby ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Family History ◽  
Research Funding ◽  
Plasma Cells ◽  
Statistical Significance ◽  
Degree Relative ◽  
First Degree Relatives ◽  
Familial Tendency ◽  
Increased Risk ◽  
History Of

Abstract Abstract 4000 Background: We have previously reported that there is an increased risk of monoclonal gammopathy of undetermined significance (MGUS) in first-degree relatives of patients with multiple myeloma (Vachon CM. Blood 2009 114: 785–790). There are several cytogenetic subtypes of myeloma, and there are no data on whether certain cytogenetic subtypes of myeloma are more frequently associated with familial MGUS. Methods: We studied patients with myeloma who participated in the familial MGUS study in whom presence or absence of MGUS in the first-degree relatives had been ascertained (Vachon CM. Blood 2009 114: 785–790). Probands were seen at the Mayo Clinic Hematology/Oncology practice (Rochester, MN, USA) between February 2006 and September 2007. Cytogenetic data was acquired via electronic medical record abstraction of fluorescence in-situ hybridization (FISH) lab reports, and used to categorize patients into one of nine cytogenetic subgroups: trisomy(ies), t(6;14), t(11;14), t(4;14), t(14;16), t(14;20), Mixed (those with trisomy(ies) and an IgH translocation), other cytogenetic abnormalities (in the absence of trisomy(ies) or IgH translocation), and normal (Kumar S. Blood 2012;119:2100–2105). We examined whether a difference in the distribution of the six primary cytogenetic categories of myeloma existed between probands with a family history of MGUS and/or myeloma and those without. Results and Conclusions: Of the 248 patients invited to participate, FISH data (with sufficient plasma cells) was available on 119 participants to establish the primary molecular cytogenetic classification of myeloma. All had available information regarding family history of MGUS and multiple myeloma. 27 had an affected first-degree relative with MGUS, and 92 did not. Distributions of cytogenetic subtypes in the two groups are shown in Table 1. IgH translocated MM was more common in myeloma patients who lacked an affected first-degree relative compared to those with familial MGUS (19% vs 30%, P=0.32) Interestingly, the t(11;14) subtype was more common in myeloma patients without familial MGUS compared to those with an first-degree relative with MGUS (19.6% vs 7.4%, P=0.24). The differences in Table 1 did not reach statistical significance, possibly due to the small numbers of individuals with a family history in this sample. However, the distribution (Table 1) suggests that the distribution of cytogenetic subtypes may be different in myeloma that is not associated with familial MGUS compared with myeloma in which a familial tendency is detected. IgH translocated MM appears to have a lower risk of familial tendency. Further investigation is needed to estimate the risk of familial MGUS within each cytogenetic subtype. Disclosures: Kumar: Merck: Consultancy, Honoraria; Millennium: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Research Funding.

Psychiatric disorder in young adults born very preterm: Role of family history

2008 ◽  
Vol 23 (7) ◽  
pp. 527-531 ◽  
Author(s):  
M. Walshe ◽  
L. Rifkin ◽  
M. Rooney ◽  
E. Healy ◽  
C. Nosarti ◽  
...  
Keyword(s):  
Young Adults ◽  
Family History ◽  
Psychiatric Disorder ◽  
Psychiatric Illness ◽  
Degree Relative ◽  
Interview Schedule ◽  
Very Preterm ◽  
Increased Risk ◽  
History Of

AbstractObjectiveTo investigate whether young adults born very preterm (VPT) (<33 weeks) are at increased risk for psychiatric illness in adulthood and whether a family history of psychiatric disorder further increases this risk.MethodsWe assessed 169 VPT and 101 term born individuals using the Clinical Interview Schedule – Revised.ResultsYoung adults born VPT had an increased risk for psychiatric disorder compared to controls (OR = 3.1, 95% CI = 1.1–8.6, p = 0.03). Those born VPT who had a history of psychiatric disorder in a first-degree relative, had an increase in risk for psychiatric disorder compared to those born VPT without a family history (OR = 5.2, 95% CI = 1.8–14.9, p = 0.002).ConclusionIndividuals born VPT are at increased risk of psychiatric illness in young adulthood compared to controls. In addition, a family history of psychiatric disorder in a first-degree relative may leave young adults born VPT particularly vulnerable to psychiatric illness.

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