Abstract

Background:

Identifying the genes that underly susceptibility to human disease represents a major objective of modern day medical research. The focus of such gene-discovery efforts has shifted from rare, monogenic conditions towards common conditions (such as diabetes, asthma, and cancers) that account for the majority of human illness and mortality.

These common conditions are termed ‘multifactorial’ because, in each case, susceptibility is attributed to the effects of genetic variation at a number of different genes and their interaction with relevant environmental exposures. Breast cancer occurring in Egypt is a model of such conditions. The median age of breast cancer in Egypt is 10 years younger than other populations, with a significant proportion occurring in very young age ranging from 20-40 years.

Aim:

The aim of this research project is the identification and characterization of the genes that provide the inherited component of susceptibility to breast cancer in Egyptian women, and how they interact with other disease determinants.

Method:

A matched case-control study where cases are identified as breast cancer patients under 45 years of age. Controls will be matched by age and social class. Controls will be confirmed as disease free by mammography and/or breast ultrasonography.

A blood sample and relevant clinical and epidemiologic data will be collected in a single visit. The blood sample will be tested for a panel of genes previously identified as associated with age or familial breast cancer including RANK ligand gene, PI3K gene, CHEK2, ATM, NBS1, RAD50, BRIP1, and PALB2 genes using a pyrosequencing platform. Exploratory analysis will be done using gene expression profiling in order to identify any emerging patterns of genes other than the panel under investigation.

Impact:

Will lead to substantial advances in our understanding of breast cancer in young women and, in turn, to improvements in diagnostic accuracy, prognostic precision, and the range and targeting of available therapeutic options.