Three common TP53 polymorphisms in susceptibility to breast cancer, evidence from meta-analysis

Abstract

The association of polymorphisms of tumor suppressor gene TP53 with breast cancer has widely been reported; however, the results are inconsistent. Here, we selected three commonly studied TP53 polymorphisms: codon 72 Arg > Pro, IVS3 16 bp Del/Ins, and IVS6 + 62A > G to explore their association with breast cancer risk by meta-analysis of published case-control studies. The results showed that codon 72 was not associated with breast cancer risk among 37 combined case-control studies (23,567 cases and 25,995 controls). However, a significant association with decreased risk of breast cancer was found in the Mediterranean studies (PP + PR vs. RR: OR = 0.32, 95% CI = 0.24-0.44, P < 0.001; PP vs. RR: OR = 0.35, 95% CI = 0.21-0.60, P < 0.001). IVS3 16 bp Del/Ins was significantly associated with an increased risk of developing breast cancer in a pooled 8 study dataset (2,470 cases and 2,825 controls; Ins/Ins + Del/Ins vs. Del/Del: OR = 1.15, 95% CI = 1.01-1.30, P = 0.04; Ins/Ins vs. Del/Del: OR = 1.75, 95% CI = 1.20-2.37, P = 0.003). No significant association was observed between IVS6 + 62A > G and breast cancer risk in a total of 10 studies (8,537 cases and 9,586 controls). These results suggest that IVS3 16 bp Del/Ins is likely an important genetic marker contributing to susceptibility of breast cancer, and codon 72 has a potential role in association with breast cancer risk within certain populations or regions.

TP53 Gene Polymorphisms in Cancer Risk: The Modulating Effect of Ageing, Ethnicity and TP53 Somatic Abnormalities

“…In this aspect, it is of note that some contradictions in the abovementioned meta-analyses could be due to age-related effects of TP53 germline variations. For example, breast cancer is one of a few diseases for which TP53 rs1042522 polymorphism raises many questions Hu et al, 2010b;Lu et al, 2011b;Ma et al, 2011;Peng et al, 2011;Sergentanis and Economopoulos, 2010b;The Breast Cancer Association Consortium, 2006;Zhang et al, 2010b;Zhuo et al, 2009a). According to our data, the C allele contributes to high breast cancer risk in the premenopausal period , whereas a combination of rs1042522, rs17878362, and rs1625895 major genotypes often occurs in postmenopausal BC (Perel'muter et al, 2008).…”

“…No significant contribution of TP53 rs1042522 polymorphism to oral cancer has been reported (Zhuo et al, 2009c). A high heterogeneity of results was observed in breast Hu et al, 2010b;Lu et al, 2011b;Ma et al, 2011;Peng et al, 2011;Sergentanis and Economopoulos, 2010b;The Breast Cancer Association Consortium, 2006;Zhang et al, 2010b;Zhuo et al, 2009a), colon and rectum (Dahabreh et al, 2010;Liu et al, 2011;Tang et al, 2010;Wang et al, 2010b) cancers. Though still not quite clear, cancer of the ovary (Schildkraut et al, 2009;Zhang et al, 2008), endometrium (Francisco et al, 2010;Jiang et al, 2010b), stomach (Francisco et al, 2010;Gao et al, 2009;Liu et al, 2011), bladder (Jiang et al, 2010a;Li et al, 2010), prostate Zhang et al, 2011b;Zhu et al, 2011), and skin (Francisco et al, 2010;Jiang et al, 2011) appear to be affected.…”

“…Though still not quite clear, cancer of the ovary (Schildkraut et al, 2009;Zhang et al, 2008), endometrium (Francisco et al, 2010;Jiang et al, 2010b), stomach (Francisco et al, 2010;Gao et al, 2009;Liu et al, 2011), bladder (Jiang et al, 2010a;Li et al, 2010), prostate Zhang et al, 2011b;Zhu et al, 2011), and skin (Francisco et al, 2010;Jiang et al, 2011) appear to be affected. As for the rs17878362 polymorphism, a clear association of the A2 allele with a high risk of breast cancer Hu et al, 2010a;Hu et al, 2010b;Zhang et al, 2011a) and a lack of involvement in lung (Hu et al, 2010a), ovary (Schildkraut et al, 2009), colon and rectum (Hu et al, 2010a) cancer susceptibility has been demonstrated. Interestingly, Peng et al did not show a dependence of breast cancer development on rs17878362 germline variation.…”

“…Interestingly, Peng et al did not show a dependence of breast cancer development on rs17878362 germline variation. For the www.intechopen.com rs1625895 polymorphism, no association with breast Hu et al, 2010b) or ovary (Schildkraut et al, 2009) cancers has been presented in the available literature.…”

The p53 codon 72 polymorphism is associated with risk and early onset of breast cancer among Saudi women

“…Similarly, the most recent meta-analysis indicated that the codon 72 polymorphism may not be associated with breast cancer risk in a Caucasian population. However, previous meta-analyses concerning the p53 codon 72 polymorphism also revealed conflicting results (23)(24)(25)(26). The precise reasons for this discrepancy remained to be elucidated (8,11).…”