Genetic epidemiology of breast cancer and associated cancers in high-risk families. II. Linkage analysis.

Chromosomal locations of hypothetical alleles which increase susceptibility to human breast cancer in some families were investigated by genetic linkage analysis. In 7 families with primarily premenopausal breast cancer and (in 5 families) ovarian cancer, a dominant susceptibility allele may be linked to the genetic marker glutamicpyruvic transaminase or alanine aminotransferase (GPT; lod score 1.95 at zero recombination). The most positive lod score for linkage to a recessive susceptibility allele was for acid phosphatase (ACP; lod score 0.78 at 40% recombination), but ACP was informative in ony 1 family. In 3 families with primarily postmenopausal breast cancer, none of 21 genetic markers provided any evidence for linkage to either dominant or recessive susceptibility alleles. In the families with the possible GPT linkage, women who carry the hypothetical susceptibility allele would be at high risk of breast cancer, whereas their relatives who do not carry that allele would have no increased risk. GPT genotype is not associated with breast cancer risk in the general population, so GPT linkage cannot be used as a screening test for breast cancer.