An evaluation of gender discrepancies in genetic referrals for BRCA testing for indicated malignancies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10584-10584
Author(s):  
Wesley Smith ◽  
Kayla Smith ◽  
William Sessions ◽  
Connor Evins ◽  
Michael Baker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Gender Gap ◽  
Genetic Screening ◽  
Metastatic Prostate Cancer ◽  
Brca Testing ◽  
Brca Mutations

10584 Background: Tumor suppressing genes BRCA1 and BRCA2 were discovered in 1990 and 1994, respectively, with mutations linked to hereditary breast-ovarian cancer syndromes (HBOCs). The discovery of these mutations has led to screening of at-risk patient populations and their family members. Women with BRCA1 or BRCA2 mutations are generally recommended to have prophylactic bilateral mastectomies and oophorectomies to decrease their future risk of cancer. While the initial discovery mostly focused on cancers in women, research has shown that BRCA mutations increase the risk of other cancers such as prostate cancer and pancreatic cancer, that also affect men. Previous research suggests that men are three times less likely to receive genetic testing in cancer driven by a 10:1 disparity in HBOC genetic testing. This was thought to be due to the lack of information on the importance of HBOC testing along with social roles in health. We wanted to evaluate the magnitude of the potential gender gap in BRCA testing in men compared to women. Methods: This was an IRB-approved, single center retrospective study to evaluate the rate of referrals to genetics for BRCA testing. Eligible patients had a personal history of cancer meeting criteria for BRCA testing per NCCN recommendations. Chart review was performed for patients with ovarian cancer, female breast cancer 45 years and younger, female triple negative breast cancer 60 years and younger, metastatic prostate cancer, all male breast cancer that have made an office visit since 2017, and pancreatic cancer since 2019. Rates of referral for genetic testing was the primary outcome and the groups were compared via the Chi-Square test. Results: 1,320 patients were included in the study, of which 664 were men and 656 were women. 128/664 (19.3%) of men were referred to genetics for screening compared to 527/656 (80.3%) for women ( p <.001). Additionally, 42/128 (32.8%) men who were referred for screening did not complete genetic screening compared to 72/527 (13.7%) women ( p <.001). A total of 62/541 (11.5%) patients who completed screening had either a BRCA1 or BRCA2 mutation. Conclusions: In our study, men were referred for BRCA testing significantly less than women for primary cancers, despite recommendation from the NCCN. In addition, men were also more than twice as likely not to complete genetic screening even if referred. The integration of genetics and oncology will continue to grow as personalized medicine continues to drive more treatment options. Closing this gender gap is important not only for familial screening purposes but also for treatment implications as patients with germline BRCA mutations are eligible for poly ADP ribose polymerase (PARP) inhibitors (e.g. olaparib) in both metastatic prostate cancer and pancreatic cancer. Further quality improvement initiatives are needed in order to close this gap by increasing education of the importance of BRCA testing in men.

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.

scholarly journals 22 The potential of serum autoantibodies against type III collagen in cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A24-A24
Author(s):  
Christina Jensen ◽  
Jeppe Thorlacius-Ussing ◽  
Patryk Drobinski ◽  
Morten Karsdal ◽  
Anne-Christine Bay-Jensen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Colorectal Cancer ◽  
Lung Cancer ◽  
Ovarian Cancer ◽  
Pancreatic Cancer ◽  
Type Iii Collagen ◽  
Healthy Controls ◽  
Type Iii ◽  
Tumor Types

BackgroundAutoantibodies are classically associated with autoimmune diseases but have recently emerged as attractive cancer biomarkers as they can be easily assessed in serum. Certain autoantibodies have been shown to promote cancer while others contribute to the body’s defense against it. Cancer progression is associated with excessive remodeling of the extracellular matrix (ECM) and collagen, but little is known about the role of autoantibodies against collagen in cancer. To investigate autoreactivity against collagen in cancer, we developed a novel biomarker assay to quantify autoantibodies against type III collagen products in serum from patients with various solid tumor types and compared levels with those find in healthy controls.MethodsThe presence and levels of autoantibodies against denatured type III collagen were measured in pretreatment serum from 223 patients with bladder cancer (n=20), breast cancer (n=20), colorectal cancer (n=20), head and neck cancer (n=20), kidney cancer (n=20), liver cancer (n=3), lung cancer (n=20), melanoma (n=20), ovarian cancer (n=20), pancreatic cancer (n=20), prostate cancer (n=20), and stomach cancer (n=20), and compared to age-matched healthy controls (n=33). Statistical differences were analyzed using the Kruskal-Wallis test adjusted for Dunn’s multiple comparisons test.ResultsSerum levels of autoantibodies against type III collagen were significantly lower in patients with bladder cancer (p=0.0007), breast cancer (p=0.0002), colorectal cancer (p<0.0001), head and neck cancer (p=0.0005), kidney cancer (p=0.005), liver cancer (p=0.030), lung cancer (p=0.0004), melanoma (p<0.0001), ovarian cancer (p<0.0001), pancreatic cancer (p<0.0001), prostate cancer (p<0.0001), and stomach cancer (p<0.0001) compared to healthy controls. This autoimmunity biomarker could discriminate between cancer and healthy controls with an AUROC value of 0.88 (p<0.0001).ConclusionsIn this study, we observed that cancer patients with different solid tumor types have downregulated levels of circulating autoantibodies directed against type III collagen compared to healthy controls suggesting that autoantibodies against type III collagen and tumor fibrosis may be important for tumor control and eradication. This autoimmunity biomarker may have the potential for studying and monitoring the close relationship between autoimmunity and cancer such as the risk of developing cancer on rheumatoid arthritis immunosuppressant or the risk of developing immune-related adverse events on cancer immunotherapy.Ethics ApprovalThe serum samples in this study were obtained from the commercial vendor Proteogenex and BioIVT, and according to the vendors, sample collection was approved by an Institutional Review Board or Independent Ethical Committee and patients gave their informed consent (Protocol numbers PG-ONC 2003/1 and WIRB® Protocol #20161665). All investigations were carried out according to the Helsinki Declaration.

Clinical management of cancer: flowcharts

2011 ◽  
Author(s):  
Thankamma Ajithkumar ◽  
Ann Barrett ◽  
Helen Hatcher ◽  
Natalie Cook
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Lung Cancer ◽  
Ovarian Cancer ◽  
Pancreatic Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Hepatocellular Cancer ◽  
Small Cell ◽  
Small Cell Lung

Bladder cancer 670Breast cancer 671Cervical cancer 672Colon cancer 673Endometrial cancer 674Epithelial ovarian cancer 675Hepatocellular cancer 676Small-cell lung cancer 677Non-small cell lung cancer 678Oesophageal cancer 679Pancreatic cancer 680Prostate cancer 681Rectal cancer 682Stomach cancer ...

scholarly journals Hereditary Pancreatic Cancer: A Retrospective Single-Center Study of 5143 Italian Families with History of BRCA-Related Malignancies

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 193 ◽  
Author(s):  
Angela Toss ◽  
Marta Venturelli ◽  
Eleonora Molinaro ◽  
Stefania Pipitone ◽  
Elena Barbieri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Pancreatic Cancer ◽  
Family History ◽  
Future Research ◽  
Brca Testing ◽  
Brca Mutations ◽  
Cancer History ◽  
Pathogenic Variants ◽  
Cancer Cluster ◽  
History Of

The identification of BRCA mutations plays a crucial role in the management of hereditary cancer prevention and treatment. Nonetheless, BRCA-testing in pancreatic cancer (PC) patients is not universally introduced in clinical practice. A retrospective analysis was conducted, firstly, to evaluate the rate of BRCA-positive families among those presenting a family history of PC besides breast and/or ovarian cancer. Secondly, the relationship between BRCA pathogenic variants and PC risk was evaluated. Finally, the characteristics of PC developed in BRCA families were described. Among 5143 family trees reporting breast and/or ovarian cancer cases, 392 showed a family history of PC. A total of 35 families (24.5% selected by the Modena Criteria and 21.3% by the NCCN Criteria) were positive to BRCA testing. Among the BRCA1 mutations, 36.8% were found within a region defined by c.3239–c.3917, whilst 43.7% of BRCA2 mutations were located within c.7180–c.8248. This study confirmed that an increase in the rate of positive tests in families with PC when associated to breast and/or ovarian tumors. Moreover, this analysis indicated two possible Pancreatic Cancer Cluster Regions that should be verified in future research. Finally, PC in families with breast and/or ovarian cancer history, particularly in BRCA families, were diagnosed at younger age and showed better one-year overall survival.

Identification and management of familial breast cancer in Austria

2017 ◽  
Vol 32 (2) ◽  
Author(s):  
Christian F. Singer ◽  
Yen Y. Tan ◽  
Christine Rappaport
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Familial Breast Cancer ◽  
Prophylactic Surgery ◽  
Management Options ◽  
Counseling And Testing ◽  
Legal Implications

AbstractAimThe aim of this study is to review the legal implications, the technology, the indications and the management of women with a familial background of breast and/or ovarian cancer.MethodsWe have reviewed the literature and national Austrian guidelines to describe the uptake of genetic counseling and the management options offered in Austria.ResultsGenetic testing for theConclusionWhile readily available country-wide counseling has led to an increase in counseling and testing, Austrian legislation mandates “non-directional counseling” resulting in a comparatively low uptake of prophylactic surgery.

scholarly journals The Cost-Effectiveness of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer in Norway

2019 ◽  
Vol 4 (1) ◽  
pp. 238146831882110 ◽  
Author(s):  
Lars Asphaug ◽  
Hans Olav Melberg
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cost Effectiveness ◽  
Gene Panel ◽  
Breast Cancer Patients ◽  
Brca Testing ◽  
Early Onset Breast Cancer ◽  
Breast And Ovarian Cancer ◽  
Quality Adjusted Life ◽  
Multigene Panel

Background. Expansion of routine genetic testing for hereditary breast and ovarian cancer from conventional BRCA testing to a multigene test could improve diagnostic yield and increase the opportunity for cancer prevention in both identified carriers and their relatives. We use an economic decision model to assess whether the current knowledge on non- BRCA mutation prevalence, cancer risk, and patient preferences justifies switching to a multigene panel for testing of early-onset breast cancer patients. Methods. We evaluated routine testing by BRCA testing, a 7-gene panel, and a 14-gene panel using individual-level simulations of annual health state transitions over a lifetime perspective. Breast and ovarian cancer incidence is reduced and posttreatment survival is improved when high-risk mutations are detected and risk-reducing treatment offered. Most model inputs were synthesized from published literature. Intermediate health outcomes included breast and ovarian cancer incidence rates, along with organ-specific cancer mortality. Cost-effectiveness outcomes were health sector costs and quality-adjusted life years. Results. Intermediate health outcomes improved by testing with multigene panels. At a cost-effectiveness threshold of $77,000, a 7-gene panel test with five non- BRCA genes was the optimal strategy with an incremental cost-effectiveness ratio of $53,310 per quality-adjusted life year compared to BRCA-only testing. Limitations. Unable to stratify carriers to specific mutations within genes, we can only make predictions on the gene level, with combined risk estimates for known variants. As mutation prevalence is the absolute upper bound of returns to more expansive testing, the rarity of modelled mutations makes analysis outcomes sensitive to model implementation. Conclusions. A 7-gene panel to diagnose hereditary breast and ovarian cancer in early-onset breast cancer patients can be a cost-effective alternative to current BRCA-only testing in Norway.

scholarly journals High frequency of BRCA recurrent mutations in a consecutive series of unselected ovarian cancer patients

2020 ◽  
Vol 28 (3) ◽  
pp. 257-266
Author(s):  
Andrei Chicos ◽  
Lucian Negura ◽  
Rares Braescu ◽  
Aliona Morariu ◽  
Anca Negura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Target Population ◽  
Consecutive Series ◽  
Inclusion Criteria ◽  
Brca Testing ◽  
Brca Mutations ◽  
Brca Genes ◽  
Incidence And Mortality ◽  
Recurrent Mutations

AbstractHereditary predisposition to breast and ovarian cancer (HBOC) is diagnosed by molecular analysis of deleterious mutations in BRCA genes, allowing oncogenetic follow-up of patients and of their families. BRCA testing addresses only to HBOC families, using restrictive inclusion criteria based on familial history of cancer and age at diagnosis. Sporadic ovarian cancer has high incidence and mortality in Romania, with low median age of diagnosis and possibly a higher magnitude of hereditary contribution comparing to othe populations. However, sporadic ovarian cancers do not qualify for BRCA testing according to inclusion criteria, and a complete BRCA screening of all cancers is neither feasible nor recommended. Despite the large diversity of BRCA mutations worldwide, some recurrent mutations have higher frequencies in diverse populations. Precisely screening for recurrent mutations in a target population allows to rapidly identifying mutation carriers without sequencing the entire BRCA genes. In Romanian population and neighboring countries, several recurrent mutations have already been described. In a consecutive series of 50 sporadic ovarian cancer patients, not qualifying for BRCA complete testing, we screened for 9 most common BRCA mutations, by multiplex-PCR, RFLP and targeted Sanger sequencing. Our results revealed 6 different BRCA mutations in 8 unrelated patients, with a frequency of 16%, much higher than expected. We further recommend screening for the identified mutations in larger series of cancer patients. The results are highly beneficial to cancer patients, healthy relatives, and overall, considering prevention in cancer a priority, to public health system and future of oncogenetics in Romania

scholarly journals Anticancer Applications and Pharmacological Properties of Piperidine and Piperine: A Comprehensive Review on Molecular Mechanisms and Therapeutic Perspectives

2022 ◽  
Vol 12 ◽  
Author(s):  
Sicon Mitra ◽  
Uttpal Anand ◽  
Niraj Kumar Jha ◽  
Mahipal S. Shekhawat ◽  
Suchismita Chatterjee Saha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Lung Cancer ◽  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Black Pepper ◽  
Piper Nigrum ◽  
Molecular Formula ◽  
Cycle Arrest

Piperine and piperidine are the two major alkaloids extracted from black pepper (Piper nigrum); piperidine is a heterocyclic moiety that has the molecular formula (CH2)5NH. Over the years, many therapeutic properties including anticancer potential of these two compounds have been observed. Piperine has therapeutic potential against cancers such as breast cancer, ovarian cancer, gastric cancer, gliomal cancer, lung cancer, oral squamous, chronic pancreatitis, prostate cancer, rectal cancer, cervical cancer, and leukemia. Whereas, piperidine acts as a potential clinical agent against cancers, such as breast cancer, prostate cancer, colon cancer, lung cancer, and ovarian cancer, when treated alone or in combination with some novel drugs. Several crucial signalling pathways essential for the establishment of cancers such as STAT-3, NF-κB, PI3k/Aκt, JNK/p38-MAPK, TGF-ß/SMAD, Smac/DIABLO, p-IκB etc., are regulated by these two phytochemicals. Both of these phytochemicals lead to inhibition of cell migration and help in cell cycle arrest to inhibit survivability of cancer cells. The current review highlights the pharmaceutical relevance of both piperine and piperidine against different types of cancers.

scholarly journals Prevalence of BRCA1 and BRCA2 Mutations Among Patients With Ovarian, Primary Peritoneal, and Fallopian Tube Cancer in India: A Multicenter Cross-Sectional Study

2021 ◽  
pp. 849-861
Author(s):  
Sudeep Gupta ◽  
Senthil Rajappa ◽  
Suresh Advani ◽  
Amit Agarwal ◽  
Shyam Aggarwal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Newly Diagnosed ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Fallopian Tube Cancer ◽  
Cross Sectional ◽  
Brca2 Mutations ◽  
Brca1 Brca2

PURPOSE There are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/ BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features. METHODS This prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/ BRCA2 mutations, and the secondary objective was to correlate BRCA1/ BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay. RESULTS Between March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively. CONCLUSION There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.

scholarly journals Association between nonalcoholic fatty liver disease and extrahepatic cancers: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Shou-Sheng Liu ◽  
Xue-Feng Ma ◽  
Jie Zhao ◽  
Shui-Xian Du ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Gastric Cancer ◽  
Pancreatic Cancer ◽  
Colorectal Adenomas ◽  
Cochrane Library ◽  
Extrahepatic Cholangiocarcinoma ◽  
Nonalcoholic Fatty Liver ◽  
Esophagus Cancer ◽  
Cancer Prostate

Abstract Background: NAFLD is tightly associated with various diseases such as diabetes, cardiovascular disease, kidney disease, and cancer. Previous studies had investigated the association between NAFLD and various extrahepatic cancers, but the available data to date is not conclusive. The aim of this study was to investigate the association between NAFLD and various extrahepatic cancers comprehensively. Methods: Searches were conducted of various electronic databases (PubMed, EMBASE, Medline, and the Cochrane Library) to identify observational studies published between 1996 and January 2020 which investigated the association between NAFLD and extrahepatic cancers. The pooled OR/HR/IRR of the association between NAFLD and various extrahepatic cancers were analyzed. Results: A total of 26 studies were included to investigate the association between NAFLD and various extrahepatic cancers. As the results shown, the pooled OR values of the risk of colorectal cancer and adenomas in patients with NAFLD were 1.72 (95%CI: 1.40-2.11) and 1.38 (95%CI: 1.22-1.56), respectively. The pooled OR values of the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in patients with NAFLD were 2.40 (95%CI: 1.75-3.31) and 2.24 (95%CI: 1.58-3.17), respectively. The pooled OR value of the risk of breast cancer in patients with NAFLD was 1.68 (95%CI: 1.44-1.97). In addition, NAFLD was also tightly associatied with the risk of gastric cancer, pancreatic cancer, prostate cancer, and esophagus cancer. Conclusions: NAFLD could significantly increase the development risk of colorectal adenomas and cancer, intrahepatic and extrahepatic cholangiocarcinoma, breast cancer, gastric cancer, pancreatic cancer, prostate cancer, and esophagus cancer.

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