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Increased risk of skin cancer in Japanese heterozygotes of xeroderma pigmentosum group A


This study was designed to learn if asymptomatic heterozygotes with mutations in a DNA repair gene are at an increased risk for cancer. To examine this, we focused on carriers of an XPA founder mutation because the frequency of xeroderma pigmentosum (XP) patients is much greater among Japanese than Caucasians, more than half of Japanese XP patients are affected at the XPA gene, and the majority of XP-A patients carry the same founder mutation in the XPA gene. Here we show that the frequency of XPA heterozygote was 14/1698 (0.8%) in cancer-free controls, and the corresponding frequency in patients with nonmelanocytic skin cancer that developed in sun-exposed areas was 11/440 (2.5%, OR = 3.08, p= 0.0097) for basal cell carcinoma, and 3/272 (1.1%, OR = 1.34, p= 0.72) for squamous cell carcinoma. These results suggest a moderately elevated risk for skin cancer among XPA heterozygotes.

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The authors are grateful to Dr. Leon Kapp for his careful reading of the manuscript, Dr. Kotaro Ozasa for his advice in selecting samples, and Dr. Charles E. Land (deceased) for his keen interest and advice to the study. Also acknowledged are Ms. T. Inoue, Ms. K. Muramoto and Mr. S. Mishima for their technical assistance and Ms. M. Utaka for manuscript preparation. The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan is a public interest foundation funded by the Japanese Ministry of Health, Labor and Welfare (MHLW) and the US Department of Energy (DOE). This research was also funded in part through a DOE award DE-HS0000031 to the National Academy of Sciences. This publication was supported by RERF Research Protocol 6-09. A part of this work was also supported by Grant-in-aid for Scientific Research from the Ministry of Education, Sports, Science and Technology (MEXT) of Japan [C-23510071], by contract HHSN261201400009C from the US National Cancer Institute (NCI) with additional support from the Division of Cancer Epidemiology and Genetics in the NCI Intramural Research Program and in part by the Intramural Research Program of the Center for Cancer Research, NCI, US. The views of the authors do not necessarily reflect those of the two governments.

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Correspondence to Yuko Hirai.

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Hirai, Y., Noda, A., Kodama, Y. et al. Increased risk of skin cancer in Japanese heterozygotes of xeroderma pigmentosum group A. J Hum Genet 63, 1181–1184 (2018).

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