Worldwide distribution of allelic variation at the progesterone receptor locus and the incidence of female reproductive cancers

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Abstract

Objectives: Global patterns of the incidence of cancer are often attributed to environmental and lifestyle differences between regions. Less attention has been given to global patterns of allelic variation of genes that may contribute to the risk of developing cancer. Methods: We genotyped samples from 21 populations for four variants of the progesterone receptor (PR) gene. One is an Alu insertion in intron 7 which defines the PROGINS haplotype. The others include a promoter region SNP 331+ G/A (rs10895068), a haplotype defining T/C substitution in intron 6 (rs561650), and an A/T substitution (rs608995) in the 3′ untranslated region of the gene. All variants have been investigated elsewhere in association with female reproductive cancers in western populations. Results: We found population differences in the frequency of each of these alleles across study populations (P < 0.01, log-likelihood G statistic, computed in FSTAT) and therefore examined the correlation between the frequency of each genetic variant and the incidence of three female reproductive cancers (breast, uterine, and ovarian) obtained from the Globocan 2008 database. Breast and ovarian cancer incidence were significantly correlated with the frequency of the Alu insertion (r = 0.86 and 0.53) and the +331 A variant (r = 0.57 and 0.73). Conclusions: Our data expand the information on genetic variation at the PR locus in non-western populations and support an argument for more work on the genetic epidemiology of cancer among nonwestern populations. © 2011 Wiley Periodicals, Inc.

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Rockwell, L. C., Rowe, E. J., Arnson, K., Jackson, F., Froment, A., Ndumbe, P., … Lorenz, J. G. (2012). Worldwide distribution of allelic variation at the progesterone receptor locus and the incidence of female reproductive cancers. American Journal of Human Biology, 24(1), 42–51. https://doi.org/10.1002/ajhb.21233

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