The frequency of Hiroshima and Nagasaki residents who are heterozygous for a founder effect mutation in the xeroderma pigmentosum A (XPA) gene

Abstract

We measured the frequency of xeroderma pigmentosum A (XPA) heterozygotes (carriers) in 1,000 Hiroshima and Nagasaki residents as a preliminary study for evaluation of excess risk of skin cancer among the XPA heterozygotes. The advantage of the study is three folds; the frequency of XP patients is over 10 times higher in Japan than in other countries, about half of them belong to group A (XPA), and 90% of these XPA cases have the same base-change mutation (a founder effect mutation). In this study, we used archival lymphocyte slides examined in the past at RERF for F1 cytogenetic studies. The DNA region that includes the founder mutation was amplified by PCR method and the amplified DNA was digested with a restriction enzyme. When the founder mutation was present, the amplified DNA was cleaved into two shorter fragments. In total, 9 founder mutations were found (4/512 in Hiroshima and 5/508 in Nagasaki, Χ²=0.12, p>0.50). The overall frequency was therefore 1/115, which is higher than the previous estimates (i.e., 1/150 to 1/240). It is likely that the latter estimates are less certain since they were based on theoretical extrapolation from small-scale clinical surveys on XP patients, and the present estimates are closer to the real.