Cancer predisposition of ataxia-telangiectasia heterozygotes

Ataxia telangiectasia genes and predisposition to leukaemia, lymphoma and breast cancer

“…In addition to five breast cancers diagnosed prospectively in a group of A-T obligate carriers, 13 other tumours were also diagnosed prospectively in the test period. Previous data had suggested that the A-T gene might additionally predispose the heterozygotes to cancers of the pancreas, stomach, bladder, ovary and CLL (Swift et al, 1990). Results from the prospective study were compatible with an elevated risk of cancer of the lung, pancreas, gall bladder and stomach.…”

The BOADICEA model of genetic susceptibility to breast and ovarian cancer

“…The polygenic component in BOADI-CEA represents the combined effects of low-penetrance breast cancer susceptibility genes. To date, only two low-penetrance breast cancer susceptibility genes, ATM and CHEK2, have been reliably identified (Swift et al, 1990;The CHEK2-Breast Cancer Consortium 2002). In the case of CHEK2, the truncating variant 1100delC confers a relative risk of breast cancer approximately two-fold; this relative risk appears to be independent of FH, and this gene fits well as a component of a multiplicative polygenic model.…”

Risk of Other Cancers in Individuals with a Family History of Pancreas Cancer

“…An autosomal recessive disorder has also been associated with increased risk of pancreas cancer. Lymphomas, ovarian, pancreas and breast cancers are part of the ataxia-telangiectasia genetic syndrome 39,40 . This syndrome is the result of defects in the ataxia telengectasia mutated gene (ATM) and results in impaired DNA double-strand break response 41 .…”

“…Of the remaining 268 case probands who were invited to participate in the study, 247 (92%) agreed. Control probands were frequency matched to case probands by age group (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59), 60-69, 70-79 years), gender, race, (African-American, Caucasian and other) and county of residence (counties were grouped into nine different areas based on population size and proximity to each other). In addition, eligible control probands were English-speaking and could be contacted by phone.…”