Re: Gutiérrez‐Enríquez S, Fernet M, Dörk T, Bremer M, Lauge A, Stoppa‐Lyonnet D, Moullan N, Angèle S, Hall J, “Functional consequences of the ATM sequence variants for chromosomal radiosensitivity”

A recent paper from Janet Hall’s DNA Repair Group at the International Agency for Research on Cancer (Gutiérrez-Enrı́quez et al., 2004) asserted that the relationship between the presence of ATM mutations or sequence variants and breast cancer predisposition is controversial and went on to claim priority for hypothesizing this association. These claims are not accurate and may mislead the medical-scientific community, thus delaying the benefits of ataxia-telangiectasia (A-T) heterozygote breast cancer research (Su and Swift, 2001) from reaching the general population. The predisposition of heterozygous carriers of A-T mutations to breast cancer has been demonstrated by rigorous studies from research groups across the United States and Europe (Swift et al. 1987, 1991; Athma et al., 1996; Larson et al., 1997–8; Izatt et al., 1999; Teraoka et al., 2001; Atencio et al., 2001; Dork et al., 2001; Sommer et al., 2003; Thorstenson et al., 2003). GutiérrezEnrı́quez et al. give too little weight to large-scale retrospective (Swift et al., 1987) and prospective (Swift et al., 1991) comparisons of breast cancer incidence in A-T families. Furthermore, this group does not even cite Athma et al. (1996), which confirmed the association using an incontrovertible, rigorous genetic method (Swift et al., 1990) based on molecular genotyping within A-T families. Recent surveys of breast cancer patients and comparison populations using robust mutation detection methods (Larson et al., 1997–8; Izatt et al., 1999; Atencio et al., 2001; Dork et al., 2001; Teraoka et al., 2001; Sommer et al., 2003; Thorstenson et al., 2003) have all reported a high frequency of A-T mutations, especially among breast cancer patients, with missense mutations constituting almost all the mutations found. Instead, Gutiérrez-Enrı́quez et al. relied on three studies (FitzGerald et al., 1997; Ramsay et al., 1998; Bebb et al., 1999) based on small and inappropriately selected subject populations and inadequate mutation detection technology (Atencio et al., 2001) and one that employed haplotype analysis rather than mutation detection (Angele et al., 2003). The fact that we do not yet know which specific missense A-T mutations of those detected in population surveys predispose to breast cancer does not justify Dr. Hall’s position that the overall association is “controversial. ” There is also no support for the priority claim by Dr. Hall’s group in the following sentence: “. lends support to our hypothesis that ATM sequence variants may contribute to hereditary radiosensitivity and breast cancer susceptibility. ” The hypothesis that A-T mutations predispose women to breast cancer was, in fact, a result of research published in a prominent journal 17 years ago (Swift et al., 1987). The United States Patent and Trademark Office has recognized the intellectual property claim based on my original discovery. Similarly, the radiosensitivity of A-T heterozygotes was first demonstrated by Malcolm Paterson and also reported in a prominent journal almost 30 years ago (Paterson et al., 1976). The subsequent studies of this topic are too numerous to cite. I ask Janet Hall’s group and Genes, Chromosomes and Cancer to promptly correct the misleading, inaccurate statements in this recent article. Sincerely,