Breast cancer risk in ataxia telangiectasia (AT) heterozygotes: haplotype study in French AT families

Epidemiological studies in ataxia telangiectasia (AT) families have suggest ed that AT heterozygotes could have an increased cancer risk, especially br east cancer (BC) in women. It has also been suggested that an increased sen sibility of AT heterozygotes to the effect of ionizing radiation could be r esponsible for the increased BC risk. BC relative risk (RR) estimation in A T heterozygotes within families ascertained through AT children is presente d here. Family data collected included demographic characteristics, occurre nce of cancers, past radiation exposures and blood samples, DNA samples wer e studied using seven ATM linked microsatellites markers allowing AT haplot ypes reconstitution. The relative risk of BC was assessed using French esti mated incidence rates. A significant increase risk of BC is found among obl igate ATM heterozygotes with a point estimate of 3.32 (P = 0.002). BC relat ive risk calculated according to age is significantly increased among the o bligate ATM heterozygotes female relatives with an age less than or equal t o 44 years (RR = 4.55, P = 0.005). The BC relative risk is statistically bo rderline among the obligate ATM heterozygote female relatives with an age g reater than or equal to 45 years (RR = 2.48, P= 0.08), The estimated BC rel ative risk among ATM heterozygotes is consistent with previously published data. However, the increased risk is only a little higher than classical re productive risk factors and similar to the risk associated with a first-deg ree relative affected by BC.