Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21

TLDR

Human breast cancer is typically driven by somatic genetic alterations, yet inherited susceptibility loci exist, notably at chromosome 17q21 in early‑onset families. The study aims to map inherited breast‑cancer genes to identify early lesions critical for general population disease development. Linkage analysis yielded a lod score of 5.98 for D17S74 in early‑onset families, with negative scores in late‑onset families, and heterogeneity likelihood ratios ranging from 2000:1 to >10⁶:1 across four loci.

Abstract

Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease. Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease. Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10 6 :1 on the basis of multipoint analysis of four loci in the region.