Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations

Abstract

The risks of cancers other than breast and ovarian amongst BRCA1 and BRCA2 mutation carriers are based on relatively few family based studies with the risk of specific cancers tested in population based samples of cancers from founder populations. We assessed risks of "other cancers" in 268 BRCA1 families and 222 BRCA2 families using a person years at risk analysis from 1975 to 2005. Cancer confirmations were overall higher than in previous family based studies at 64%. There was no overall increase in risk for BRCA1 carriers although oesophagus had a significant increased RR of 2.9 (95% CI 1.1-6.0) and stomach at 2.4 (95% CI 1.2-4.3), these were based mainly on unconfirmed cases. For BRCA2 increased risks for cancers of the pancreas (RR 4.1, 95% CI 1.9-7.8) and prostate (RR 6.3, 95% CI 4.3-9.0) and uveal melanoma (RR 99.4, 95% CI 11.1-359.8) were confirmed. Possible new associations with oesophagus (RR 4.1, 95% CI 1.9-7.8) and stomach (RR 2.7, 95% CI 1.3-4.8) were detected but these findings should be treated with caution due to lower confirmation rates. In contrast to previous research a higher risk of prostate cancer was found in males with mutations in the BRCA2 OCCR region. The present study strengthens the known links between BRCA2 and pancreatic and prostate cancer, but throws further doubt onto any association with BRCA1. New associations with upper gastro-intestinal malignancy need to be treated with caution and confirmed by large prospective studies.

Histopathological, Molecular, and Genetic Profile of Hereditary Diffuse Gastric Cancer: Current Knowledge and Challenges for the Future

“…Germline BRCA2 mutations predispose to hereditary breast and ovarian cancer. In some families with BRCA2 mutations, an increased incidence of GC has been encountered [40][41][42][43], with one family fulfilling the HDGC criteria [35].…”

Erratum: Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

“…There remains debate about whether there is an increased risk of PrCa associated with BRCA1 mutations, with some studies reporting no increased risk to those reporting a 1.8-3.75 fold increased risk (Thompson et al, 2002;Leongamornlert et al, 2012;Moran et al, 2012). A number of studies have reported that BRCA2 mutation carriers have more aggressive disease, suggested by their younger age at diagnosis, higher rates of lymph node involvement and distant metastasis at diagnosis, and higher mortality rates compared with non-carriers (Tryggvadóttir et al, 2007;Mitra et al, 2008;Edwards et al, 2010;Gallagher et al, 2010;Thorne et al, 2011;Castro et al, 2013).…”

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

“…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].…”

“…Numerous reports have debated whether an increased lifetime risk for any cancer beyond breast and ovarian cancer even exists across both sexes and genes [10,12]. Multiple studies have agreed on a significantly increased risk of pancreatic and prostate cancers in BRCA mutation carriers; however, further information regarding the lifetime risks of these cancers is needed [5,7,13,14].…”

“…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].…”