Absence of the common Insulin-like growth factor-1 19-repeat allele is associated with early age at breast cancer diagnosis in multiparous women.

Multiparity decreases the risk of breast cancer in white women, whereas it is a risk factor in black women < 50 years. Early-onset breast cancer (< 50 years) has been associated with high insulin-like growth factor-I (IGF-I) levels. Absence of the common IGFI 19 cytosine-adenine ( CA)- repeat allele (IGFI-19/-19) inverts the effect of several non-genetic factors on breast cancer risk but the interaction between IGFI-19/-19 and multiparity on breast cancer risk is unknown. As IGFI-19/-19, multiparity and early-onset breast cancer are more common in black than in white women, we aimed to study whether multiparity combined with IGFI-19/-19 increases the risk of early-onset breast cancer. Four hundred and three breast cancer patients diagnosed in Lund, Sweden, at age 25 - 99 years were genotyped for the IGFI CA-repeat length using fragment analysis. Overall, 12.9% carried the IGFI-19/-19 genotype. There was a highly significant interaction between multiparity and IGFI-19/-19 on age at breast cancer diagnosis ( P = 0.007). Among IGFI-19/-19 patients, multiparity was associated with a 9.2 year earlier age at diagnosis compared with uniparity or nulliparity ( P = 0.006). Multiparity combined with IGFI-19/-19 was associated with an early age at breast cancer diagnosis. If confirmed, IGFI-19/-19 may help identify a subgroup of women for earlier breast cancer screening.