DNA repair germline pathogenic mutation associations with treatment duration and family history in prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 245-245
Author(s):  
James Vu ◽  
Marcus Marie Moses ◽  
Lahiru Ranasinghe ◽  
Patrick Cotogno ◽  
Charlotte Manogue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Dna Repair ◽  
Family History ◽  
Treatment Outcomes ◽  
Treatment Duration ◽  
Pathogenic Mutation ◽  
Germline Mutations ◽  
Cancer Type ◽  
History Of

245 Background: Germline mutation testing for metastatic prostate cancer patients creates a potential opportunity to personalize targeted therapies to improve treatment outcomes. The goal of this study was to characterize cancer family history, and evaluate treatment outcomes, in mCRPC patients with DNA repair pathogenic germline alterations. Methods: A retrospective study of metastatic PCa patients at Tulane Cancer Center identified 246 patients undergoing germline testing using panels (30-80 genes) (Color.com or Inviate.com). Clinical annotations included family history, life-extending treatments, and treatment duration. Statistical analyses including chi-square and Wilcoxon Rank Sum. Results: In the 246 patients tested for germline mutations, 27 patients (11.0%) had ≥1 DNA repair germline pathogenic mutation (BRCA2 = 11, BRCA1 = 3, CHEK2 = 5, ATM = 3, NBN = 1, PMS2 = 2, MSH2 = 1, PALB2 = 1) while 219 patients (89.0%) possessed no pathogenic mutation in these genes. Patients with a DNA repair pathogenic mutation were more likely to have > 2 family members affected by cancer, regardless of cancer type or degree of relationship (p = 0.04). In the DNA repair population, 5 pathogenic patients had no family history of cancer (18.5%, n = 5). Patients were more likely to have a germline alteration if they had 1 or more first degree relatives affected with breast cancer (p = 0.00001). Median lines of life-extending treatments to date between the pathogenic and non-pathogenic population were equal at 2. There were no significant differences in treatment duration for abiraterone (p = 0.49), enzalutamide (p = 0.99), docetaxel (p = 0.28), cabazitaxel (p = 0.53), carboplatin+docetaxel (p = 0.41), or radium-223 (p = 0.59) between the two groups. Conclusions: In this study, DNA repair pathogenic germline mutations did not affect treatment durations or lines of therapy but these studies are underpowered. The relationship between a family history of breast cancer and a DNA repair pathogenic mutation has not previously been reported.

Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5568-5568
Author(s):  
Elisa Marie Ledet ◽  
Ellen Jaeger ◽  
Whitley Hatton ◽  
Marcus W. Moses ◽  
Alexandra Sokolova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Dna Repair ◽  
African American ◽  
Family History ◽  
Metastatic Prostate Cancer ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
Brca Mutations ◽  
Repair Genes

5568 Background: The relevance of germline mutations in metastatic prostate cancer is well established; however, comparison of germline genetics in African American (AA) versus Caucasian (CA) men with metastatic prostate cancer (PCa) is limited. Methods: Germline data from self-identified AA and CA metastatic PCa patients (pts) were collected from 5 academic cancer centers. Various commercial cancer-specific germline testing panels were used to evaluate 12-86 genes. Pathogenic (P) or likely pathogenic (LP) mutations, and variants of unknown significance (VUS), were reported according to ACMG guidelines. Self-reported family history (FH) was annotated for 99% of pts. Statistical analyses included Chi-squared and Fischer’s exact tests. Results: A total of 821 metastatic PCa pts were assessed: 152 AAs and 669 CAs. For P/LP alterations, AAs had a frequency of 11.2% (17/152) as compared to a frequency of 14.6% (98/669) in CAs (p = 0.302). AA pts were more likely to have a VUS than CA pts, 61% vs 43% respectively (OR = 2.09, 95%CI [1.45, 2.99], p < 0.001). BRCA mutations were similar between races, but AA were more likely to have a BRCA1 P/LP alteration (OR = 6.00, 95% CI [1.33, 27.09], p = 0.025). AA pts were less likely to have a P/LP alteration in a non-BRCA gene (OR = 0.34, 95% CI [0.15, 0.80], p = 0.013). Among DNA repair genes, there were no significant difference between AA and CA pts (p = 0.574); however, there was a trend toward AA pts having fewer P/LP alteration in a non-BRCA DNA repair genes (OR = 0.26, 95% CI [0.06, 1.08], p = 0.071). In pts with >1 first degree relative (FDR) with ovarian cancer, P/LP germline alterations were more likely in CAs (OR = 2.33, 95% CI [1.05, 5.17], p = 0.043); but there were no significant differences in AAs (p = 0.098). Those with >2 FDRs with PCa were more likely to have a P/LP change in CAs (OR = 2.32, 95% CI [1.04, 5.15], p = 0.043), but there were no difference in AAs (p = 0.700). In pts with ≥2 FDRs with breast cancer, P/LP germline alterations were more likely in both AAs (OR = 9.36, 95% CI [1.72, 50.84], p = 0.019) and CAs (OR = 3.92, 95% CI [1.79, 8.59], p = 0.001). Conclusions: We did not observe a difference in the overall frequency of germline P/LP alterations between AA and CA men with metastatic PCa but VUSs were more common in AA men. These AA men have an overall frequency of BRCA mutations similar to CA men; however, BRCA1 mutations were more prevalent in these AAs. Non-BRCA P/LP mutations are significantly less frequent in AA pts. A positive family history of >2 FDRs with breast cancer was associated with P/LP alterations in both AA and CA pts.

Family history and germline alterations in metastatic prostate cancer patients.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 231-231
Author(s):  
Whitley Hatton ◽  
Ellen Jaeger ◽  
Marcus W. Moses ◽  
Alexa Zaheri ◽  
Patrick Cotogno ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Metastatic Prostate Cancer ◽  
Family Members ◽  
Prostate Cancer Risk ◽  
Pathogenic Mutation ◽  
Cancer Center ◽  
Cancer Type ◽  
Pathogenic Mutations ◽  
History Of

231 Background: Recent literature has highlighted the importance of germline genetic testing in metastatic prostate cancer (PCa)patients (pts). This retrospective study evaluated family history (FH), evaluate treatment outcomes in metastatic patients with pathogenic germline mutations, and compared family history in Caucasian (CA) and Africans Americans (AA). Methods: At Tulane Cancer Center, 428 metastatic PCa pts had germline testing in at least 79 genes. Comprehensive family histories were obtained in all. Analysis of prevalent FH, including breast, ovarian, prostate, and pancreatic cancers was assessed for all metastatic pts. Statistical analyses including chi square were performed. Results: 64 (64/428; 14.9%) pts had at least one or more pathogenic mutations, while 166 (166/428; 38.7%) had were normal. The remaining 199 (199/428; 46.4%) of pts had a variant of uncertain significance (VUS). Pts with a DNA repair pathogenic mutation were more likely to have >2 family members affected by cancer, regardless of cancer type or degree of relationship (p=0.0047); 6 pts without any family history of cancer had a pathogenic mutation. In CA, the presence of either a breast or PCa family history was associated with pathogenic germline findings (p=.022/.0367) However, in AAs neither breast nor prostate cancer predicted pathogenic germline alterations. Conclusions: The correlation between family history of breast and PCa cancer in CA pts with pathogenic mutations is notable as is the finding of >2 family members with cancer predicting germline pathogenic alterations. With AA pathogenic pts, there was no correlation of family history of breast and PCa, which highlights the need to learn more about the genetic factors which influence AA prostate cancer risk.[Table: see text]

Germline mutations in DNA repair genes in a large series of unselected Chinese prostate cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17523-e17523
Author(s):  
Yu Wei ◽  
Yao Zhu ◽  
Junlong Wu ◽  
Dingwei Ye ◽  
Hao Zeng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Genetic Testing ◽  
Family History ◽  
High Risk ◽  
Cancer Patients ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
History Of ◽  
Repair Genes

e17523 Background: Germline DNA repair gene (DRG) mutations has emerged as a potential determinant of cancer risk and therapeutic response in PCa. Despite substantial advances in delineating the germline mutation in DRGs among Caucasian population, the prevalence of mutations in DRGs are largely unknown among a large series of unselected prostate cancer patients in Chinese population. Methods: We enrolled 1003 prostate cancer patients from three different hospitals in China, unselected for family history of cancer or age at diagnosis. All patients received germline genetic testing using a clinician-selected multi-gene panel. The 18 DNA repair genes and HOXB13, which has established or emerging potential clinical actionability in PCa, were analyzed in our study. Results: A total of 94 (9.7%) deleterious germline mutations were identified among the 1003 unselected prostate cancer patients. Of these, 5.6% patients carried a BRCA1 or BRCA2 mutations (5.2% in BRCA2 and 0.4% in BRCA1), 3.6% patients carried other DRG mutations (including 10 genes) and 0.5% patients carried HOXB13 mutations. Besides, variants with uncertain significance (VUS) were found in approximately 45% patients. We also divided 633 metastatic PCa patients into 542 de novo metastastic PCa and 91 recurrent metastastic PCa and found mutation frequencies did not differ between these two groups (9.0% vs 11.6%, p = 0.6). Patients with younger age of onset or family history of cancers were more likely to harbour germline mutations in DRGs. However, the rate of germline mutations were still at a high level for patients more than 70 years old (6.7%) and patients without family history of cancers (7.5%). There is no statistically significant difference in the mutation frequencies between patients with metastasis and without metastasis (7.5% vs 9.2%, p = 0.4), which may be because 85% patients without metastasis in our cohort were in high to very high risk group or have lymph node metastasis. Conclusions: To our knowledge, our study reported the largested series of Chinese PCa patients who received germline genetic testing. Our study provided a rationality for germline genetic testing criteria from high risk to metastastic PCa regardless of family history considering the high proportion. In addition, we recommended a multigene panel covering 13 genes ( ATM, BRCA1, BRCA2, CHEK2, FANCA, HOXB13, MSH2, MSH6, NBN, PALB2, RAD51C, RAD51D, TP53) in China. Nevertheless, the high prevalence of VUS (45%) in Chinese PCa patients warrant further efforts.

scholarly journals Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Joaira Bakkach ◽  
Mohamed Mansouri ◽  
Touria Derkaoui ◽  
Ali Loudiyi ◽  
ElMostafa El Fahime ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Brca2 Gene ◽  
Germline Mutations ◽  
Genetic Alterations ◽  
Early Onset Breast Cancer ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
History Of

Abstract Background To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco. Methods Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform. Results Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer. Conclusion Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.

scholarly journals First-degree family history of breast cancer is associated with prostate cancer risk: a systematic review and meta-analysis

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zheng-Ju Ren ◽  
De-Hong Cao ◽  
Qin Zhang ◽  
Peng-Wei Ren ◽  
Liang-Ren Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Systematic Review ◽  
Family History ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Prostate Cancer Risk ◽  
History Of

scholarly journals 1053 Sleep Duration And Timing Associated With History Of Breast Prostate And Skin Cancer: Data From A Nationally-representative Sample

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A400-A400
Author(s):  
B Piro ◽  
S Garland ◽  
P Jean-Pierre ◽  
B Gonzalez ◽  
A Seixas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Skin Cancer ◽  
Cancer Survivors ◽  
Sleep Duration ◽  
Sleep Disturbances ◽  
Sleep Problems ◽  
Cancer Type ◽  
Cancer Data ◽  
History Of

Abstract Introduction Sleep disturbances are a common problem among cancer survivors. Also, cancer patients can have altered circadian rhythms and these changes can continue to affect the patient long after the conclusion of their treatment. This analysis aims to investigate how the sleep and wake times of cancer survivors differ from the rest of the population, depending on the type of cancer. Methods Data from the 2015-2016 National Health and Nutrition Examination Survey were used. Population-weighted data on N=5,581 individuals provided complete data. History of breast, prostate, and skin cancer (melanoma or other) was self-reported. Sleep duration was self-reported in half-hour increments, and typical bedtime and waketime was self-reported. Covariates included age, sex, and race/ethnicity. Weighted linear regressions with sleep duration, bedtime and waketime were examined, with each cancer type as predictor. Results Prevalence was 1.7% for prostate cancer, 1.5% for breast cancer, 2.3% for non-melanoma skin cancer, and 0.8% for melanoma. In adjusted analyses, prostate cancer was associated with an additional 26.5 minutes of average total sleep (95%CI 2.2,50.9, p=0.03), a 23.1 bedtime minutes earlier (95%CI -40.4,-5.8, p=0.009), and no difference in waketime. Breast cancer was associated with a bedtime that was 41.1 minutes later (95%CI 10.3,72.0, p=0.009) and a waketime that was 48.7 minutes later (95%CI 12.5,84.9, p=0.008), but no difference in sleep duration. No statistically significant effects were seen for either type of skin cancer, melanoma or non-melanoma. Conclusion Prostate cancer was associated with an earlier bedtime and associated increased sleep time. Breast cancer, on the other hand, was associated with a phase delay of the sleep period but no change in sleep duration. Skin cancer was not associated with differences in sleep duration or timing. These findings may have implications for not only treatment of sleep problems in different types of cancer, but also possible circadian mechanisms. Support Dr. Grandner is supported by R01MD011600

Germline mutations in early-onset or hereditary breast cancer from the Middle East.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 20-20 ◽  
Author(s):  
Makia J Marafie ◽  
Rabea Al-Temaimi ◽  
Andre Megarbane ◽  
Fahd Al-Mulla
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Middle East ◽  
Middle Eastern ◽  
Germline Mutations ◽  
Illumina Platform ◽  
Family History Of Cancer ◽  
Middle Eastern Women ◽  
History Of ◽  
History Of Cancer

20 Background: Breast cancer is the most common cancer affecting women of Middle Eastern origin. Epidemiologically, breast cancer in the Middle East clusters in families and usually affects women a decade younger than Western women. This dilemma is compounded by the lack of curated databases and ambitious studies that address the roles genetic or genomic may play in breast cancer. Methods: We have exome sequenced 60 Middle Eastern women with moderate and strong family history of cancer or young women without significant family history of cancer. DNA extracted from peripheral blood of patients and matching normal Middle Eastern women without history of familial or sporadic cancers, were subjected to whole-exome sequencing using the HiSeq 2500 Illumina platform and MLPA to map major breast cancer–activating genetic defects. Results: Several novel BRCA1/2 mutations were identified in the minority of these women. However, other complex mutations in non-BRCA1/2 genes appear to play a more subtle role in breast cancer in the Middle Eastern women. Germline mutations in TP-53, BARD1 and mismatch repair genes were more frequent than expected by chance. Conclusions: BRCA1/2 gene mutations are not a significant cause of heritable cancers in the Middle East. The region may benefit from a well-curated region-specific database accessible to clinicians and scientists where clinical and variants information can be deposited from all over the Middle East.

scholarly journals Prevalence of germline TP53 mutation among early onset middle eastern breast cancer patients

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abdul Khalid Siraj ◽  
Tariq Masoodi ◽  
Rong Bu ◽  
Sandeep Kumar Parvathareddy ◽  
Kaleem Iqbal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Middle Eastern ◽  
Mutation Screening ◽  
Univariate Analysis ◽  
Positive Family History ◽  
Germline Mutations ◽  
Pathogenic Mutations ◽  
History Of

Abstract Background The data on prevalence and clinical relevance of TP53 germline mutations in early onset Middle-Eastern breast cancer (BC) is limited. Methods We determined TP53 germline mutations in a cohort of 464 early onset BC patients from Saudi Arabia using capture sequencing based next generation sequencing. Results Germline TP53 pathogenic mutations were found in 1.5% (7/464) of early onset Saudi BC patients. A total of six pathogenic missense mutations, one stop gain mutation and two variants of uncertain significance (VUS) were detected in our cohort. No TP53 pathogenic mutations were detected among 463 healthy controls. TP53 mutations carriers were significantly more likely to have bilateral breast cancer (p = 0.0008). At median follow-up of 41 months, TP53 mutations were an unfavorable factor for overall survival in univariate analysis. All the patients carrying TP53 mutations were negative for BRCA1 and BRCA2 mutations. Majority of patients (85.7%; 6/7) carrying TP53 mutation had no family history suggestive of Li-Fraumeni Syndrome (LFS) or personal history of multiple LFS related tumors. Only one patient had a positive family history suggestive of LFS. Conclusions TP53 germline mutation screening detects a clinically meaningful risk of early onset BC from this ethnicity and should be considered in all early onset BC regardless of the family history of cancer, especially in young patients that are negative for BRCA mutations.

scholarly journals Family History of Breast Cancer and Breast Cancer Risk Between Malays Ethnicity in Malaysia and Indonesia: A Meta-Analysis

2019 ◽  
Author(s):  
Ricvan Dana NINDREA ◽  
Teguh ARYANDONO ◽  
Lutfan LAZUARDI ◽  
Iwan DWIPRAHASTO
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Random Effect ◽  
Cancer Type ◽  
History Of ◽  
Published Research ◽  
Random Effect Models

Background: Breast cancer is the most common cancer type in women not only in world but also in Malays ethnicity between Malaysia and Indonesia. Breast cancer has varying incidence in every country, but genetic factor by family history influence the incidence of breast cancer. This systematic review and meta-analysis was performed to determine family history of breast cancer and breast cancer risk between Malays ethnicity in Malaysia and Indonesia. Methods: This meta-analysis was conducted on published research articles on family history of breast cancer and breast cancer risk between Malays ethnicity in Malaysia and Indonesia published between Jan 1999 and Jul 2018 in the online article databases of PubMed, ProQuest and EBSCO. Pooled odds ratios (OR) were calculated with fixed and random-effect models. Publication bias was visually evaluated by using funnel plots and statistically assessed through Egger’s and Begg’s tests. Data were processed using Review Manager 5.3 (RevMan 5.3) and Stata version 14.2 (Stata Corporation). Conclusion: This analysis confirmed the association of family history of breast cancer and breast cancer risk between Malays ethnicity in Malaysia and Indonesia.

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