Variation in breast cancer risk of heterozygotes for ataxia-telangiectasia according to environmental factors.
Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder, characterized by progressive neuronal degeneration, immunological deficiency, radio-sensitivity and an increased risk of cancer. Although several studies have confirmed that AT heterozygosis increases the risk of breast cancer (BC), we do not know how exogenous factors affect this risk. We performed an epidemiological study on the cancer risks associated with AT heterozygosis in France and explored the variation in BC risk according to environmental factors, such as reproductive factors and exposure to ionizing radiation. Information on the amount of ionizing radiation received by an individual in their lifetime and on their reproductive life was collected from the living relatives of 34 AT children (175 female relatives). Consistent with previous reports and with our previous estimate on the entire retrospective cohort, we found that the risk of developing BC is 3.6-fold higher among ATM heterozygous women. An increased risk was associated with an early age at menarche, a late age at first childbirth, nulliparity, premenopausal status and increasing periods of breast cell mitotic activity (BCMA) prior to the first childbirth. Age at menarche, age at 1st childbirth and BCMA seemed to have a stronger effect in ATM heterozygotes than in non-ATM heterozygotes. However, the tests were not all statistically significant (only age at 1st childbirth). Surprisingly, the risk of BC decreased when the chest or breasts were irradiated. It is difficult to interpret the data because of the small sample size, but further investigations should provide a biological explanation for the variation in BC risk associated with exogenous factors according to ATM heterozygosis status.
Geoffroy-Perez
Béatrice
B
Inserm EMI00-06, Tour Evry 2, 523 Place des Terrasses d l'Agora, 91034 Evry Cedex, France.
Janin
Nicolas
N
Ossian
Katia
K
Laugé
Anthony
A
Stoppa-Lyonnet
Dominique
D
Andrieu
Nadine
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004777:Environment; D005260:Female; D006579:Heterozygote; D006801:Humans; D007743:Labor, Obstetric; D008572:Menarche; D008875:Middle Aged; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D013997:Time Factors; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases