Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients

Choi, Min Chul; Heo, Jin Hyung; Jang, Ja‐Hyun; Jung, Sang Geun; Park, Hyun; Joo, Won Duk; Lee, Chan; Lee, Je Ho; Lee, Jun Mo; Hwang, Yoon Young; Kim, Seung Jo

doi:10.1097/igc.0000000000000529

Cited by 27 publications

(43 citation statements)

References 18 publications

(15 reference statements)

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“…There is currently no available in silico test to predict the functional effect of in-frame deletions/ duplications; however, c.8437_8439delGGA was detected in the sister of a patient in the present study, who had been diagnosed with breast cancer at her age of 45 years. This coincident detection was analyzed using a cosegregation test, and these results, together with previously report, 9 suggest that c.8437_8439delGGA is likely pathogenic.…”

Section: Pathogenicity Of 3 Identified Uvssupporting

confidence: 73%

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Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer

Choi

Jang

Jung

et al. 2018

International Journal of Gynecological Cancer

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Section: Pathogenicity Of 3 Identified Uvssupporting

confidence: 73%

“…9 Variations were described according to the Human Genome Variation Society (http://www.hgvs.org/mutnomen) and the Breast Cancer Information Core (BIC; http://research.nhgri.nih.gov/bic/) nomenclature systems.…”

Section: Direct Sequencingmentioning

confidence: 99%

Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer

Choi

Jang

Jung

et al. 2018

International Journal of Gynecological Cancer

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“…The incidence rates differed by cancer site: for example, at age 60 years, the absolute risk (per 10,000 person years) of colorectal cancer in control siblings was 6.55 (95% CI: 5.86-7.31) compared to 16 (Table 2a). From age-stratified analysis, younger siblings had the highest IRR for colorectal cancer, breast cancer and prostate cancer, but the IRR was highest in 40-50 year old siblings for melanoma, although this was of similar magnitude to the IRR in the youngest siblings (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). The IRRs for each cancer decreased with age and were relatively stable in older ages.…”

Section: Absolute Risk Of Cancer By Agementioning

confidence: 88%

“…[36][37][38][39] We also found high familial aggregation of breast cancer at younger ages consistent with reports of higher prevalence of mutations in the BRCA1/BRCA2 genes in young patients and a high probability of the same gene mutations in their sisters. 40,41 Examining the changing risk with time since the index person's diagnosis, we found the pattern varied by cancer site: for colorectal and breast cancer, the risk profile for siblings was approximately constant for up to 20 years while for melanoma there was evidence of a small decline in risk in the first 5 years, and for prostate cancer a sharp decline. To further investigate the decreasing pattern for prostate cancer we investigated the incidence in case and control siblings during the first 2 years after the index diagnosis, stratifying by whether the diagnosis was before/after 1997, when PSA testing was widely available in Sweden.…”

Section: Epidemiologymentioning

confidence: 92%

Patterns of changing cancer risks with time since diagnosis of a sibling

Lee

Czene

Rebora

et al. 2014

Intl Journal of Cancer

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Family history is a well-known risk factor for many cancers. However, it is important to know if/how the familial risk of cancer changes over time. For each of four major cancers (colorectal, breast, prostate and melanoma), we identified siblings of cancer patients (case siblings) and siblings of matched cancer-free controls sampled from Swedish population-based registers. Effects of age and time since diagnosis on sibling risks were examined using Poisson regression and presented graphically as smoothed hazard ratios (HRs). Screening effects were investigated by comparing hazards before/after the introduction of mammography for breast cancer and prostate-specific antigen (PSA) testing for prostate cancer. Case siblings had higher cancer incidence than control siblings for all cancers at all ages, with overall incidence rate ratios (IRRs) of 2.41 (95% confidence interval 2.14-2.71) for colorectal cancer, 2.37 (2.24-2.52) for breast cancer, 3.69 (3.46-3.93) for prostate cancer and 3.20 (2.72-3.76) for melanoma. Risks were highest in siblings who were young when the first cancer was diagnosed in the family, with siblings aged 30-40 having IRR 9.05 (3.03-27.00) for colorectal cancer and 4.30 (2.87-6.45) for breast cancer. Smoothed HRs remained fairly constant for up to 20 years except for prostate cancer, where the HR decreased steeply during the first few years. After introduction of PSA testing, men had higher incidence of prostate cancer shortly after diagnosis in a brother, but no such screening effect was found for breast cancer. Our findings can help inform the screening and counseling of family members of cancer patients.Family history is long recognized as an important risk factor for cancer and has also been found to be associated with cancer prognosis. One of the main, but simple, ways to begin to understand cancer etiology is by identifying the involvement of heritable genes through investigation of familial aggregation. There is a large body of published research providing estimates of increased risk for various cancer sites in different types of relatives. [1][2][3][4] However, in addition to the estimates of overall or lifetime increased risk in family members, it is important to know if/how this risk changes over time. To address this question, different time scales need to be considered when studying the relatives at risk: current age, age at the time of diagnosis of the first cancer in the family, elapsed time from the cancer diagnosis and calendar time.Age is the strongest risk factor for cancer onset and many studies show both the age of relatives and the age of the cancer patient at diagnosis to be associated with the family cancer risk. 5,6 Young age at onset of cancer has been shown to have high heritability and so is an important factor in familial risk. 7,8 However, few studies have investigated in detail how this risk changes with time since the first (index) cancer diagnosis in a family. 9 Such risk profiles would not only provide insight into underlying etiology but could also be used to ...

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“…BRCA1 c.5470_5477del is another highly repeated site found three times in our study. Internationally, the site has been previously identified in Korean sample (30), while nationally it has been reported in Shanghai (31), Beijing (32), Zhejiang, and Liaoning (33). Thus far, it has been found in 12 unrelated carriers from six different areas of China, including HBOC patients (33.3%) (32), sporadic BC patients (33.3%) (31,33) and early-onset BC (33) or BBCpatients (33.3%) (the present study).…”

Section: Discussionmentioning

confidence: 99%

Multicenter cross‑sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations

et al. 2018

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Abstract. Due to lack of systematic reviews, BRCA, DNA Repair Associated (BRCA) mutations in the Chinese population are not completely understood. The following study investigates the prevalence and type of BRCA mutations in Chinese patients with high hereditary risk of breast cancer (BC).Patients Drwere recruited from 14 cities between October 2015 and February 2016, and were selected based on family and personal medical history. BRCA mutations were analyzed by collecting blood samples from all participants. 437 BC patients were included. A total of seventy-six (17.4%) mutation carriers were identified with no geographic difference. The mutation rate in the early-onset BC patients was lower compared to family history of breast/ovarian cancer (OC), bilateral BC, male BC, BC&OC or meeting ≥2 criteria (9.2 vs. 21.7, 24.0, 22.2, 16.7 and 24.3%, respectively, P=0.007). A total of 61 mutation sites were identified (BRCA1 32, BRCA2 29) including 47.5% novel sites and extra 10 variants of uncertain significance. A total of five sites were repeated in more than one unrelated patient. A total of 11 sites were associated with hereditary breast and ovarian cancer syndrome, two of which were confirmed by family pedigrees. Compared with BRCA -patients, patients with BRCA1 mutation tended to be triple-negative BC (P<0.001), whereas patients with BRCA2 mutation were more likely to be hormone receptor positive

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Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients

Abstract: The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified.

Cited by 27 publications

References 18 publications

Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer

Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer

Patterns of changing cancer risks with time since diagnosis of a sibling

Multicenter cross‑sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations

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