Latitude may modify the effect of TP53 codon 72 polymorphism on cancer risk

Abstract

AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Recent meta-analyses have examined the association between the TP53 arginine/proline polymorphism at codon 72 (Arg72Pro) and the risk of breast cancer,1 lung cancer,2 gastric cancer,3 and cervical cancer.4 A critical reanalysis of the most recent meta-analyses was performed to examine whether the effect of Arg72Pro is modified by latitude. Latitude was assigned to all 108 studies that were included in the 4 aforementioned meta-analyses.1-4 A metaregression was performed to determine whether latitude may modify the effect of the C allele (dominant model). Latitude was treated as a binary variable (0, latitude less than or equal to the median; 1, latitude greater than the median). The analysis was performed using STATA 10.0 software (Stata Corporation, College Station, Tex). The median latitude for the meta-analyses was 40.78 in breast cancer, 37.06 in lung cancer, 33.43 in gastric cancer, and 37.55 in cervical cancer. Concerning breast cancer in Caucasians (32 studies), greater latitude was associated with a more limited protective effect of the G (Arg) allele (exponentiated coefficient, 1.75, 95% confidence interval [CI], 1.22-2.49; P = .003). No significant association was detected in Asians. Regarding lung cancer, greater latitude tended to intensify associations between the C (Pro) allele and cancer in Caucasians at a borderline level (16 studies; exponentiated coefficient, 1.39; 95% CI, 0.93-2.07; P = .097). Such an effect was not observed for either Asian or mixed populations. Concerning gastric cancer and cervical cancer, no significant effects were demonstrated. Consequently, the results indicate that latitude may modify the effect of Arg72Pro on the risk of breast cancer and possibly on the risk of lung cancer. It is striking that, in both cancer types, increasing latitude pointed in the same direction, ie, enhancement of the association between the C allele and cancer. This occurred although Arg72Pro status mediated the opposite effects; the C allele was a risk factor for lung cancer2 but protected from breast cancer.1 These results imply that the effect of latitude may surpass tissue-specific associations. It is noteworthy that, after contemplating genotype frequencies, an impressive analogy emerges: as latitude increases, the C allele becomes rare5 and simultaneously seems to confer additional cancer risk. REFERENCES 1 Zhang Z, Wang M, Wu D, et al. P53 codon 72 polymorphism contributes to breast cancer risk: a meta-analysis based on 39 case-control studies. Breast Cancer Res Treat. 2010; 120: 509- 517. 2 Dai S, Mao C, Jiang L, Wang G, Cheng H. P53 polymorphism and lung cancer susceptibility: a pooled analysis of 32 case-control studies. Hum Genet. 2009; 125: 633- 638. 3 Zhou Y, Li N, Zhuang W, et al. P53 codon 72 polymorphism and gastric cancer: a meta-analysis of the literature. Int J Cancer. 2007; 121: 1481- 1486. 4 Klug SJ, Ressing M, Koenig J, et al. TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. Lancet Oncol. 2009; 10: 772- 784. 5 Beckman G, Birgander R, Sjalander A, et al. Is p53 polymorphism maintained by natural selection? Hum Hered. 1994; 44: 266- 270. Theodoros N. Sergentanis MS*, Konstantinos P. Economopoulos MD*, * School of Medicine University of Athens Athens, Greece. Citing Literature Volume116, Issue1415 July 2010Pages 3523-3523 ReferencesRelatedInformation