Multiple primary cancers as a guide to heritability

Abstract

There are approximately 100 genes which when mutated are known to predispose to one or more forms of cancer. Currently, genetic testing is offered for many of these, either as single genes or as multi‐gene panels. Features of hereditary cancer include a positive family history of cancer, early age of onset and the appearance of multiple primary cancers in one individual. In some cases multiple cancers may be of the same site (e.g., bilateral breast cancer) and in other cases they may be at different sites. Various combinations of cancer sites may be indicative of specific cancer syndromes such as the breast ovarian cancer syndrome. Genetic testing should be offered to individuals who have experienced multiple primary cancers in some circumstances, the genetic counselor should review the ages of sites of cancer, their pathologic features and the family history of cancer as part of the pre‐test evaluation.

Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma

“…BAP1 knockdown in MM cell lines has been paradoxically associated to a decreased proliferation, with an accumulation of cells in the S phase of the cell cycle 22 , suggesting that BAP1 loss might promote tumorigenesis inducing a delayed, but more permissive, G1/S checkpoint 22 . Heterozygous germline mutations of other important tumor suppressor genes, such as BRCA1 , CDKN2A , and RB1 , increase risk of cancer specifically to one or very few anatomical sites 39 . One of the few tumor suppressor genes whose germline heterozygosity, similar to BAP1, is associated to increased risk of cancer to several sites is TP53 , which encodes p53 39 .…”

“…Heterozygous germline mutations of other important tumor suppressor genes, such as BRCA1 , CDKN2A , and RB1 , increase risk of cancer specifically to one or very few anatomical sites 39 . One of the few tumor suppressor genes whose germline heterozygosity, similar to BAP1, is associated to increased risk of cancer to several sites is TP53 , which encodes p53 39 . Besides its well-known intrinsic functions, recently a novel non-cell-autonomous tumor suppressor effect of p53 has been described, via regulation of macrophage polarization and cytokine release 40 .…”

A regional population‐based hereditary breast cancer screening tool in Italy: First 5‐year results

“…Hereditary breast ovarian cancer (HBOC) can be defined as a genetic disorder in which breast and ovarian malignant tumors seem to cluster within families . The main factors that suggest a hereditary cancer predisposition syndrome are young age at cancer diagnosis, multiple tumors, bilateral tumors, presence of rare tumors, several cancer‐affected relatives, autosomal dominant inheritance and, in some cases, ethnicity . Families with these characteristics should be referred to specialized hospital/centers that offer cancer risk assessment and genetic counseling…”

Germline mutation and aberrant transcripts of WWOX in a syndrome with multiple primary tumors

“…The occurrence of multiple primary tumors is relatively rare, especially in young people. Inherited genetic defects are one of the most possible pathogenic factors that predispose young subjects to cancers or multiple primary tumors . Chan et al reported that deleterious germline mutations were identified in one‐third (38/110) of patients with multiple primary tumors, spanning 11 known cancer predisposition genes including BRCA1 , BRCA2 , mismatch repair genes ( MLH1 , MSH2 , MSH6 ), TP53 , APC , ATM , MUTYH , PALB2 , and RAD50 .…”