Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian

Abstract

Background Previous studies have reported additional cancers associated with BRCA mutations; however, type, magnitude of risk, and gender differences remain to be clarified. The purpose of this study was to evaluate the incidence of cancers other than breast and ovarian cancer in known mutation carriers. Methods An institutional review board approved study identified 1072 patients who had genetic counseling at our institution and tested positive for a deleterious BRCA mutation. The expected number of cancer cases was calculated from the number of individuals in the study sample multiplied by the general population cancer incidence rates. The expected and observed number of cases were calculated in 5 year intervals to accommodate different age-related incidence rates. Standardized incidence ratios (SIRs) for each cancer type were calculated. Results We identified 1177 cancers in the 1072 mutation carriers comprising 30 different cancer types. Individuals with a BRCA1 mutation did not have a significant increase in cancers other than breast and ovarian; however, a trend in melanoma was observed. Individuals with a BRCA2 mutation had a significantly higher number of observed cases compared to expected cases for pancreatic cancer (SIR = 21.7, 95%CI = 13.1–34.0, p value <0.001) in both men and women and prostate cancer in men (SIR = 4.9, 95%CI = 2.0–10.1, p value =0.002). Conclusions The results of this study uphold the current recommendations for HBOC screening of cancers other than breast and ovarian by the National Comprehensive Cancer Network. Larger cohorts and collaborations are needed to further verify these findings.

Cancer Incidence in First- and Second-Degree Relatives of BRCA1 and BRCA2 Mutation Carriers

“…The results confirm the recognized increased incidence of breast and ovarian cancer in women with a BRCA mutation. Additionally, our results further confirm an association between BRCA mutations and pancreatic cancer.The increased SIRs for breast and ovarian cancer in both BRCA1 and BRCA2 families and for pancreatic cancer in BRCA2 families are consistent with the results from Mersch et al [9], who examined the incidence of non-breast and ovarian cancers in BRCA mutation-positive individuals. The cohort analyzed in the study by Mersch et al [9] represent most of the index cases used to obtain the population of FDRs and SDRs in our study.The increased incidence of prostate cancer in BRCA2 mutation carriers found by Mersch et al [9] was also supported by our findings when analyzing only FDRs in the study population.…”

“…One of the larger studies to date, completed by the Breast Cancer Linkage Consortium in 1999 found BRCA2 mutation carriers have an increased risk of prostate and pancreatic cancer and an increased risk of buccal cavity, pharyngeal, stomach, gallbladder, andbile ductcancers and melanoma of theskin [5].Theincreased risk of prostate and pancreatic cancer has been replicated by numerous other studies, and the association between BRCA2 mutations and these cancers is accepted in clinical practice [5][6][7][8][9][10][11].…”

“…In 2014, Mersch et al [9] completed a large singleinstitution study of the incidence of non-breast and ovarian cancers in more than 1,000 known BRCA mutation carriers from our institution. They found an increased incidence of pancreatic and prostate cancer in BRCA2 mutation carriers and an increased occurrence of melanoma in BRCA1 carriers and cervical cancer in BRCA2 carriers [9].Various other studies have reported an increased risk of melanoma of the skin and cervical, gallbladder, stomach, and uterine cancers; however, these increases have ranged from one-to fourfold, have varied between BRCA1 and BRCA2 mutations, and have been inconsistently reported [5,7,[10][11][12].…”

Effectiveness and Safety of Poly (ADP-ribose) Polymerase Inhibitors in Cancer Therapy: A Systematic Review and Meta-analysis

“…About 20% of breast cancer patients were BRCA mutations carriers [51,52]. Beyond breast cancer, several other malignancies, including ovarian cancer, pancreatic cancer, melanoma, and prostate cancer, were also correlated to BRCA mutations [53]. On top of BRCA, mutations of other DNA repair genes, such as RAD51, ATM, PALB2, CHEK2, may also increase sensitivity to PARP inhibitors [54].…”

Hereditäres Magen- und Pankreaskarzinom

“…Bei 90-95 % der Patientinnen besteht eine Mutation im BRCA1-oder BRCA2-Gen [45]. Aber auch für andere Tumoren ist das Risiko erhöht [31].…”