Prevalence and characteristic cancer in families with BRCA1 and BRCA2 mutations

School of Medicine, University of California San Francisco, San Francisco, CA 94115, USA.
Familial Cancer (Impact Factor: 1.98). 11/2008; 8(2):153-8. DOI: 10.1007/s10689-008-9220-x
Source: PubMed


A growing body of research describes cancers other than breast and ovarian in families with BRCA1/2 mutations, but the prevalence and characteristics of pancreatic cancer in these families has not been well described. This study was designed to: (1) estimate the prevalence of pancreatic cancer in BRCA1/2 positive families; (2) ascertain age of onset and gender distribution of pancreatic cancer in this cohort; and (3) compare age and gender characteristics of pancreatic cancer in BRCA1/2 positive families with those of the general population. Within the UCSF Cancer Risk Program cohort, 24/219 (11.0%) BRCA1 and 17/156 (10.9%) BRCA2 families had at least 1 individual with pancreatic cancer. In the 24 BRCA1 families, median age of diagnosis was 59 (range 45-80) in males, and 68 (range 38-87) in females (male:female ratio = 2.00). In the 17 BRCA2 families, median age of diagnosis was 67 (range 39-78) in males and 59 (range 46-81) in females (male:female ratio = 1.11). The SEER database, which describes cancer characteristics in a representative sample of the US population, reports a median age of 70 in males and 74 in females (male:female ratio = 0.96) over the same time period. Additionally, mean ages of diagnosis of pancreatic cancer in BRCA1/2 families differ significantly from the SEER mean (P = 0.0014 for BRCA1 and P = 0.011 for BRCA2 by unpaired t-test). Our findings suggest that families with early onset pancreatic cancer and features of hereditary breast and ovarian cancer should be considered for BRCA1/2 testing.

9 Reads
  • Source
    • "The onset of cancer was earlier than in general population : 59 in males and 69 in females in BRCA1families and 67 in males and 59 in females in BRCA2 families (Kim et al., 2009). Compared to SEER data which showed a 0.96:1 male:female ratio occurence of pancreatic cancer in general population, in BRCA1 families, showed a 2:1 male: female ratio, possible linked to the competing mortality for breast and ovarian cancer in their female relatives (Kim et al., 2009). For these reasons, males under 65 years old in families with a strong history of breast, ovarian, and pancreatic cancer be considered for BRCA1/2 testing along with their female relatives. "

    Pancreatic Cancer - Molecular Mechanism and Targets, 12/2011; , ISBN: 978-953-51-0410-0
  • Source
    • "It is well known that BRCA1 and/or BRCA2 mutation carriers have increased risks for pancreatic and prostate cancers Kim et al., 2009; Agalliu et al., 2009). In normal individuals, chronic inflammation in the target organ predisposes to either cancer. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Women who inherit a defective BRCA1 or BRCA2 gene have risks for breast and ovarian cancer that are so high and seem so selective that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. All these suggestions share the assumption that some disabled function of normal tumor suppressor genes leads to a tissue specific cancer response. Here the idea is proposed and tested that major determinants of where BRCA1/2 hereditary cancers occur are the tissue specificity of the cancer pathogen, the agent that causes chronic inflammation or the carcinogen. The target tissue may have receptors for the pathogen, become selectively exposed to an inflammatory process or to a carcinogen such as during digestion. An innate genomic deficit in a tumor suppressor gene such as BRCA1/2 contributes because it exacerbates the susceptibility to disease wherever it attacks. This hypothesis also fits data for several tumor suppressors beyond BRCA1/2. A major advantage of this model is that it suggests there may be some options in addition to prophylactic surgery.
  • Source
    • "The role of CHEK2 in sporadic pancreatic cancer development has not been studied so far, however, it has been shown that the risk of pancreatic cancer development is increased in several hereditary cancer syndromes resulting from inherited mutations in genes directly involved in DNA repair pathways (e.g. BRCA1, BRCA2) [9]. Our previous studies on the Czech population have shown significant associations of alterations flanking to or localized within the CHEK2 forkhead-associated (FHA) domain-coding region (residues 112–175; containing the most prevalent CHEK2 mutation – I157T) with the increased risk of sporadic colorectal but not breast cancer [10] [11]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Checkpoint kinase 2 gene (CHEK2) alterations increase risk of several cancer types. We analyzed selected CHEK2 alterations in 270 Czech pancreatic cancer patients and in 683 healthy controls. The pancreatic cancer risk was higher in individuals who inherited rare alterations in CHEK2 region involving forkhead-associated domain other than I157T (OR=5.14; 95% CI=0.94-28.23) but the observed association was non-significant (p=0.057). The most frequent I157T mutation did not alter the pancreatic cancer risk and neither the followed deletion of 5395bp nor c.1100delC were found in any of pancreatic cases. We conclude that the I157T, other alterations in its proximity, del5395 and c.1100delC in CHEK2 do not predispose to pancreatic cancer risk in the Czech population.
    10/2010; 34(5):656-8. DOI:10.1016/j.canep.2010.06.008
Show more


9 Reads
Available from