Abstract
Genes encoding the serine proteinase inhibitor B family (SERPINBs) are mainly clustered on human chromosome 18 (18q21). Several serpins are known to affect malignant phenotypes of tumor cells, so aberrant genetic variants in this molecular family are candidates for conferring susceptibility for risk of cancer. We investigated whether eight selected non-synonymous variations within SERPINB loci at 18q21 might be associated with risk of prostate cancer in Japanese men. A case-control study involving 292 prostate-cancer patients and 384 controls revealed significant differences in regard to distribution of four missense variations in genes encoding plasminogen activator inhibitor 2 (PAI2) and SERPINB10. The most significant association was detected for the N120D polymorphism in the PAI2 gene (P=5.0×10−5); men carrying the 120-N allele (120-N/N and 120-N/D genotypes) carried a 2.4-fold increased risk of prostate cancer (95% confidence interval 1.45–4.07). Associations were also detected for three other missense polymorphisms in those two genes. Strong linkage disequilibrium in the region encompassing PAI2 and SERPINB10 extended to about 50 kbp. The results suggested that missense variations in one or both of these genes confer important risks for prostate cancer, and may be themselves tumorigenic. Although confirmative replication studies on larger cohorts are awaited, clinical examination of these variations may become useful for identifying individuals at high risk for prostate cancer.
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Acknowledgements
We thank Mitsuko Kajita, Mina Kodaira, and Miho Kawagoe for their expert technical assistance. This work was supported by a grant for Strategic Research from the Ministry of Education, Science, Sports, and Culture of Japan; by a Research Grant for Research from the Ministry of Health and Welfare of Japan; and by a Research for the Future Program Grant of the Japan Society for the Promotion of Science.
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Shioji, G., Ezura, Y., Nakajima, T. et al. Nucleotide variations in genes encoding plasminogen activator inhibitor-2 and serine proteinase inhibitor B10 associated with prostate cancer. J Hum Genet 50, 507–515 (2005). https://doi.org/10.1007/s10038-005-0285-1
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DOI: https://doi.org/10.1007/s10038-005-0285-1
