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

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.

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Risk of Dysglycemia in Pregnancy amongst Kenyan Women with HIV Infection: A Nested Case-Control Analysis from the STRiDE Study

Journal of Diabetes Research ◽

10.1155/2021/8830048 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Sonak D. Pastakia ◽

Wycliffe K. Kosgei ◽

Astrid Christoffersen-Deb ◽

Benson Kiragu ◽

John N. Hector ◽

...

Keyword(s):

Family History ◽

Pregnant Women ◽

Gestational Age ◽

Fasting Glucose ◽

Case Control ◽

Oral Glucose ◽

Control Analysis ◽

History Of ◽

Women With Hiv ◽

Nested Case Control

Introduction. Gestational diabetes is a common complication, whose incidence is growing globally. There is a pressing need to obtain more data on GDM in low- and middle-income countries, especially amongst high-risk populations, as most of the data on GDM comes from high-income countries. With the growing awareness of the role HIV plays in the progression of noncommunicable diseases and the disproportionate HIV burden African countries like Kenya face, investigating the potential role HIV plays in increasing dysglycemia amongst pregnant women with HIV is an important area of study. Methods. The STRiDE study is one of the largest ever conducted studies of GDM in Kenya. This study enrolled pregnant women aged between 16 and 50 who were receiving care from public and private sector facilities in Eldoret, Kenya. Within this study, women received venous testing for glycosylated hemoglobin (HbA1c) and fasting glucose between 8- and 20-week gestational age. At their 24-32-week visit, they received a venous 75 g oral glucose tolerance test (OGTT). Because of the pressing need to assess the burden of GDM within the population of pregnant women with HIV, a nested case-control study design was used. Pregnant women with HIV within the larger STRiDE cohort were matched to non-HIV-infected women within the STRiDE cohort at a 1 : 3 ratio based on body mass index, parity, family history of GDM, gestational age, and family history of hypertension. The measurements of glucose from the initial visit (fasting glucose and HbA1c) and follow-up visit (OGTT) were compared between the two groups of HIV+ cases and matched HIV- controls. Results. A total of 83 pregnant women with HIV were well matched to 249 non-HIV-infected women from the STRiDE cohort with marital status being the only characteristic that was statistically significantly different between the two groups. Statistically significant differences were not observed in the proportion of women who developed GDM, the fasting glucose values, the HbA1c, or OGTT measurements between the two groups. Discussion. Significant associations were not seen between the different measures of glycemic status between pregnant women with and without HIV. While significant differences were not seen in this cohort, additional investigation is needed to better describe the association of dysglycemia with HIV, especially in Kenyan populations with a higher prevalence of GDM.

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Male Breast Cancer: Surgical and Genetic Features and a Multidisciplinary Management Strategy

Breast Care ◽

10.1159/000501711 ◽

2019 ◽

Vol 15 (1) ◽

pp. 14-21 ◽

Cited By ~ 1

Author(s):

Francesca Pellini ◽

Eleonora Granuzzo ◽

Silvia Urbani ◽

Sara Mirandola ◽

Marina Caldana ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

High Risk ◽

Male Breast Cancer ◽

Brca2 Mutation ◽

Positive Family History ◽

Male Breast ◽

Mutation Carriers ◽

History Of ◽

Clinical Records

Background: Male breast cancer (MBC) is a rare disease with a rising incidence trend. The major risk factors related to MBC are a positive family history of breast cancer (BC) and BRCA1/2 mutations, which indicate a relevant genetic role. Methods: In this retrospective series, we enrolled 69 male patients presenting with male breast cancer (MBC) between 01/01/1992 and 31/12/2018, and 26 high-risk not-affected men presenting between 01/01/2016 and 31/12/2018. Participants’ electronic clinical records were reviewed. Patients’ data reported age at diagnosis, tumor characteristics, therapeutic management, and BRCA1/2 status as well as a family history of breast, ovarian, or prostate cancer (PCa) in first-degree relatives. Results: We analyzed 69 MBC patients. Median age was 64 years. The majority of tumors diagnosed were of an early TNM stage. The most frequent histological subtype was invasive ductal carcinoma (76.7%). Hormone receptors were positive in >90% of MBC cases. Nearly all patients underwent modified radical mastectomy or total mastectomy. Adjuvant endocrine therapy was delivered in 59.4%. Among MBC-affected patients, we recorded a high percentage of a positive family history of BC. Mutational analysis for the BRCA1/2 genes was performed in 17 MBC patients; 11.8% were carriers of BRCA2 pathogenic mutations. Among 26 healthy high-risk subjects included in this case series, 4 were BRCA1 mutation carriers and 9 were BRCA2 mutation carriers. Discussion: We evaluated the distribution of clinicopathological characteristics in MBC subjects and assessed the frequency of mutations in the BRCA genes in affected patients and healthy high-risk subjects, with the aim of proposing a surveillance program for BC and PCa.

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Hospital visitors as controls in case-control studies

Revista de Saúde Pública ◽

10.1590/s0034-89102001000500005 ◽

2001 ◽

Vol 35 (5) ◽

pp. 436-442 ◽

Cited By ~ 5

Author(s):

Gulnar Azevedo S Mendonça ◽

José Eluf-Neto

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Family History ◽

Case Control ◽

Breast Size ◽

Case Control Studies ◽

Family History Of Cancer ◽

History Of ◽

Incident Cases ◽

History Of Cancer

OBJECTIVE: Selecting controls is one of the most difficult tasks in the design of case-control studies. Hospital controls may be inadequate and random controls drawn from the base population may be unavailable. The aim was to assess the use of hospital visitors as controls in a case-control study on the association of organochlorinated compounds and other risk factors for breast cancer conducted in the main hospital of the "Instituto Nacional de Câncer" -- INCA (National Cancer Institute) in Rio de Janeiro (Brazil). METHODS: The study included 177 incident cases and 377 controls recruited among female visitors. Three different models of control group composition were compared: Model 1, with all selected visitors; Model 2, excluding women visiting relatives with breast cancer; and Model 3, excluding all women visiting relatives with any type of cancer. Odds ratios (OR) and 95% confidence intervals were calculated to test the associations. RESULTS: Age-adjusted OR for breast cancer associated with risk factors other than family history of cancer, except smoking and breast size, were similar in the three models. Regarding family history of all cancers, except for breast cancer, there was a decreased risk in Models 1 and 2, while in Model 3 there was an increased risk, but not statistically significant. Family history of breast cancer was a risk factor in Models 2 and 3, but no association was found in Model 1. In multivariate analysis a significant risk of breast cancer was found when there was a family history of breast cancer in Models 2 and 3 but not in Model 1. CONCLUSIONS: These results indicate that while investigating risk factors unrelated to family history of cancer, the use of hospital visitors as controls may be a valid and feasible alternative.

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15165 ◽

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.

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PALB2 germline mutations in familial breast cancer cases with personal and family history of pancreatic cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-010-1305-1 ◽

2010 ◽

Vol 126 (3) ◽

pp. 825-828 ◽

Cited By ~ 28

Author(s):

Paolo Peterlongo ◽

Irene Catucci ◽

Graziella Pasquini ◽

Paolo Verderio ◽

Bernard Peissel ◽

...

Keyword(s):

Breast Cancer ◽

Pancreatic Cancer ◽

Family History ◽

Familial Breast Cancer ◽

Germline Mutations ◽

History Of

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Adult weight gain and central obesity in women with and without a family history of breast cancer: a case control study

Familial Cancer ◽

10.1007/s10689-007-9122-3 ◽

2007 ◽

Vol 6 (3) ◽

pp. 287-294 ◽

Cited By ~ 6

Author(s):

Michelle N. Harvie ◽

Saba Bokhari ◽

Andrew Shenton ◽

Linda Ashcroft ◽

Gareth Evans ◽

...

Keyword(s):

Breast Cancer ◽

Weight Gain ◽

Family History ◽

Central Obesity ◽

Case Control Study ◽

Case Control ◽

Adult Weight ◽

History Of ◽

Control Study

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Lifestyle factors and breast cancer in a Moroccan population case-control study of the center Mohammed VI for cancer treatment

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20194343 ◽

2019 ◽

Vol 8 (10) ◽

pp. 3825

Author(s):

Drissi Houda ◽

Imad Fatima Ezzahra ◽

Bendahhou Karima ◽

Benider Abdelatif ◽

Radallah Driss

Keyword(s):

Breast Cancer ◽

Family History ◽

Cancer Treatment ◽

Case Control Study ◽

Case Control ◽

Childhood And Adolescence ◽

Overweight Women ◽

History Of ◽

Post Menopause ◽

Control Study

Background: The study aims to examine the association between lifestyle habits and breast cancer risk in a Moroccan population.Methods: This is a case-control study conducted at the Mohammed VI Centre for cancer treatment in Casablanca.Results: The results highlighted that family history of breast cancer (OR=5.73) and alcohol consumption (OR=3.76) were positively associated with breast cancer. Analysis of anthropometric parameters showed that the risk of developing breast cancer is estimated at 1.78 in overweight women and 2.39 in obese women compared to those of normal weight. The risk of developing breast cancer is estimated at 1.82 for women with a WC greater than 88 cm and 1.70 for women with a WHR greater than 0.85. At age 10, the risk is 1.60 for women with a large figure compared to women with a small figure. However, at age 40, the average body shape relative to the lean body was associated with a decreased risk of breast cancer. In addition, the data confirmed that physical activity participation decreases with age; in childhood and adolescence, women are more active while in post-menopause, women become moderately active. Being very active in childhood, peri-menopause and post-menopause seems to be a protective factor against the occurrence of breast cancer.Conclusions: The study showed that the risk of breast cancer is potentially high in elderly women, overweight women and women with a family history of cancer. This risk was increased by behavioral factors such as toxic habits and physical inactivity.

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Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22226 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22226-e22226

Author(s):

A. Kwong ◽

L. Wong ◽

C. Wong ◽

F. Law ◽

E. Tang ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

High Risk ◽

Breast Cancers ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Mutation Carriers ◽

History Of ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

e22226 Background: Breast cancers due to underlying germline BRCA1 and BRCA2 mutations are associated with particular pathological features that may differ from sporadic breast cancers. We report clinical and pathologic characteristics of breast cancer in a clinical cohort of high risk Chinese women with BRCA mutations and those without mutations. Methods: 202 high risk women based on their age and family history were recruited from March 2007 to November 2008. Medical information was prospectively collected from the patients and medical records. BRCA1 and BRCA2 mutations were detected using full gene sequencing and multiplex ligation-dependent probe amplification (MLPA). Results: Of the 202 female probands tested, 25 (12.3 %) were BRCA mutation carriers of which 11 (44%) were BRCA1 and 14 (56%) were BRCA2 mutations. Breast cancer risk factors, other than family history, did not differ between carriers and non-carriers. Mutation carriers were more likely to have a familial history of breast cancer (p=0.07) and personal and family history of ovarian cancer (p=0.005; p=0.007). Other cancers found in carriers families included pancreatic, gastric, colon, lung, liver, and nasopharyngeal. 23% of women diagnosed with DCIS had BRCA mutations compared with 11.4% of those with invasive cancers. BRCA related tumors were more likely to be ER, PR and Her-2 negative (Triple negative, TN) (p= 0.006). Overall 9.6% of non-BRCA cancers were TN whereas 25.9% of BRCA cancers were TN. Prevalence of TN in BRCA1 carriers is 71% compared with 13.4% in BRCA2 carriers. BRCA1 mutation related cancers were significantly more likely to be ER negative than BRCA2 and this is only significant in those who are under 40 years of age (p=0.070). Conclusions: We have a high BRCA2 mutation rate in our cohort. BRCA related breast cancer is associated with families with increasing number of first degree relatives with breast and/or ovarian cancers and were higher for DCIS cancers. Prevalence of TN breast cancers was high compared to Caucasian cohorts. BRCA mutations were associated with pathologically, poor prognostic features (TN and high grade) especially in younger women. No significant financial relationships to disclose.

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

10.21203/rs.3.rs-396248/v1 ◽

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.

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