Genetic predisposition to breast cancer

Abstract

Breast cancer is the most common cancer among American women. Because metastatic breast cancer is an incurable disease, efforts to decrease breast cancer mortality have focused on early detection and improved treatment. Identification and analysis of a specific genetic susceptibility could permit detection of susceptible women and greatly increase the understanding of the initial step that eventually leads to cancer. Because susceptibility loci have been recognized as sites that often are altered during tumor progression, the identification and cloning of such loci could be important in developing cancer therapies. In this article, the progress being made in segregation analysis, linkage analysis, and cloning of breast cancer susceptibility loci is reviewed. The evidence for genetic inheritance is most consistent with dominant inheritance for at least three major susceptibility loci. Proliferative breast disease has been hypothesized to be an inherited lesion in breast cancer kindreds with both pre‐menopausal and postmenopausal probands. Currently, there are many genetic markers for mapping the human genome, Technologic advances have progressed from restriction fragment length polymorphisms to highly polymorphic markers. Using this technology, breast cancer susceptibility in some kindreds with an early onset has been shown to be linked to chromosome 17q. Gene isolation eventually will follow with an increased understanding of the percentage of breast cancer cases that are a result of this genetic locus. Li‐Fraumeni syndrome, which often is expressed as breast cancer, is due to mutations in the p53 gene. Characterization of the syndrome and its relationship to the altered gene should proceed rapidly. There is also a group of families exhibiting a genetic susceptibility that is not due to either of these loci. Together, these findings indicate that there are at least three separate major loci segregating for breast cancer susceptibility. With the current initiative to map and sequence the entire human genome and the advances that recently have been reported, a detailed molecular understanding of breast cancer predisposition can be envisaged.

Clinical Characteristics of Cutaneous Melanoma and Second Primary Malignancies in a Dutch Hospital-Based Cohort of Cutaneous Melanoma Patients

“…More recent, familial syndromes of melanoma and tumours of the nervous system [44], breast cancer [45], and/or pancreatic cancer [45–49] have been documented. Furthermore, melanoma clusters in families with familial retinoblastoma, Li-Fraumeni cancer syndrome, and Lynch syndrome type II [42, 50, 51]. In our study the most frequent cancer among relatives was, as expected on the basis of above mentioned literature, breast cancer, followed by intestinal cancer and lung cancer.…”

Clinico-morphological patterns of breast cancer including family history in a New Delhi hospital, India-A cross-sectional study

“…Family history is another risk-factor for breast carcinoma. It has been noted that women who have first degree relative with breast cancer have a risk two to three times that of general population, the risk further increased if the relative was affected at an early age and/or had bilateral disease [ 20 ]. There is a greater risk if more than one close relative is affected, if breast cancer has occurred at a young age in a family member or if a patient has bilateral disease [ 30 ].…”

“…While the epidemiological studies for breast cancer carried out in India have largely focused on risk factors such as, religion, age at menarche, menopause and reproductive history, not much attention has been paid on role of family history even though genetic predisposition is responsible for 5–10% of all breast cancers [ 8 - 17 ]. It is well known that the hereditary factors play a far greater role in women for the development of breast cancer [ 18 - 20 ]. Data so far available is from the western studies.…”

Population-Based Relative Risks for Lung Cancer Based on Complete Family History of Lung Cancer

“…An inherited predisposition has been shown to contribute to a number of cancers. [1][2][3][4] Recognition of the role of inherited predisposition has only been more recently recognized for lung cancer, likely due to the strength of association with tobacco use. [5][6][7] Estimated relative risks (RRs) for lung cancer based on family history have been published, but are typically restricted to first-degree relatives (FDRs) only.…”