Rs1042522

This SNP, a variant in the TP53 gene, is 1 of 25 SNPs reported to represent independently minor, but cumulatively significant, increased risk for breast cancer. [PMID 17341484]

For details of all 25 SNPs in this group, along with the two methods used to calculate overall risk estimates for breast cancer, refer to the SNPedia breast cancer entry.

For this particular SNP, the G allele encodes an arginine at position 72 of the protein (where there's normally a proline), and the SNP is commonly called the Arg72 variant, although P72R and Arg72Pro are also common in the literature.

[PMID 18256523] Minor allele homozygotes, i.e. rs1042522(C;C) genotypes, live on average 3 years longer than major allele (G;G) homozygotes, based on a study of 9,200+ Danish individuals. The increased longevity is speculated to be related to the increased apoptosis seen for this gain of function SNP, presumably due to "increased robustness" during the period of treatment after the diagnosis of life-threatening diseases such as cancer of certain types.

A study of 148 individuals with advanced nonsmall cell lung cancer (NSCLC) concluded rs1042522(G;G) genotypes were more likely to be resistant to first-line chemotherapy, especially the irinotecan plus cisplatin regimen, than those with (C;G) or (C;C) genotypes (60% vs 27%, p = .014). In multivariate analysis, the (G;G) genotype was strongly predictive for shorter progression-free survival (PFS) (hazard ratio [HR] = 1.952, p = .01).[PMID 18618574]

A study of 57 patients with advanced gastric cancer treated with paclitaxel and cisplatin combination chemotherapy found that rs1042522(G;G) and rs1042522(C;G) genotypes were significantly correlated with a lower response rate (and worse progression) to the combination chemotherapy when compared to rs1042522(C;C) homozygotes (35.7 vs. 66.7%, p-value 0.019).[PMID 19052714]

rs1042522 is not associated with SLE in a study of Caucasians, African-Americans, and Asian children and adults.[PMID 19074170]

Implicated in type-2 diabetes based on a study of 1,161 Finnish patients.[PMID 18678618]

• [PMID 19193430] rs2279744, rs1042522, rs17878362 and rs1625895 associated with high grade endometrial cancer

spittoon African Americans with rs1042522(G;G) in the p53 gene were 2.15 times more likely to die of colorectal cancer than those with one or no copies of a G at this SNP. In Caucasians there was no association between survival and rs1042522.

spittoon rs1042522(A) might have had an easier time conceiving in colder temperatures

10.1073/pnas.0904280106 The P72 allele was found to be significantly enriched over the R72 allele among in vitro fertilization (IVF) patients. The P72 allele serves as a risk factor for implantation failure. LIF levels are significantly lower in cells with the P72 allele than in cells with the R72 allele, which may contribute to the decreased implantation and fertility associated with the P72 allele.

[PMID 19367277] Patients with variant TP53 genotypes either for the Arg72Pro or the PIN3 polymorphism were at increased risk of telangiectasia, a late skin side effect of radiotherapy following breast-conserving surgery. Odds ratios were 1.66 for 72Pro carriers and 1.95 for PIN3 A2 allele carriers. Carrying both variant alleles led to a doubling of risk.

Venter snp
Source	plos
Gene	TP53
allele	C
frequency	0.233
sift	TOLERATED
HuRef	1103645273472
Disease Association	Defects in TP53 are a cause of choroid plexus papilloma (MIM:260500). Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.

[PMID 19423538] Common Genetic Variation in TP53 and Risk of Human Papillomavirus Persistence and Progression to CIN3/Cancer Revisited

[PMID 19471604] Lack of association between p53 gene polymorphisms and primary open angle glaucoma in the Japanese population

[PMID 19505915] Association of Genetic Polymorphisms, mRNA Expression of p53 and p21 with Chronic Benzene Poisoning in a Chinese Occupational Population

[PMID 19521721] Accelerated decline in lung function in cigarette smokers is associated with TP53/MDM2 polymorphisms

[PMID 19286843] Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma

[PMID 19707196] The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers

[PMID 19834951] The Li-Fraumeni syndrome (LFS): a model for the initiation of p53 signatures in the distal Fallopian tube

[PMID 19837266] TP53 R72P and MDM2 SNP309 polymorphisms in modification of childhood acute lymphoblastic leukemia susceptibility

[PMID 20110284] Genotype and haplotype analysis of TP53 gene and the risk of pancreatic cancer: an association study in the Czech Republic

[PMID 20127253] The role of TP53 and p21 gene polymorphisms in breast cancer biology in a well specified and characterized German cohort

[PMID 20357201] Association of Polymorphisms of Tumor Necrosis Factor and Tumor Protein p53 with Primary Open Angle Glaucoma: A Replication Study of Ten Genes in A Chinese Population

[PMID 20512840] Association between TP53 gene ARG72PRO polymorphism and chromosome aberrations in human cancers

[PMID 20544687] Evidence that genetic variants of metabolic detoxication and cell cycle control are not related to gallbladder cancer risk in Chilean women

[PMID 20593380] p53 Pro72Arg polymorphism and prostate cancer in men of African descent

[PMID 20615891] TP53 Arg72Pro Polymorphism and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis

[PMID 20587610] Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection

[PMID 20232390] Genetic variations of DNA repair genes and their prognostic significance in patients with acute myeloid leukemia

[PMID 21790896] Genetic and environmental predictors, endogenous hormones and growth factors and risk of estrogen receptor-positive breast cancer in Japanese women

[PMID 21843334] TP53 and MDM2 gene polymorphisms and risk of hepatocellular carcinoma in Italian patients

[PMID 22184967] [Association analysis of polymorphic loci of TP53 and NFKB1 genes with human age and longevity]

[PMID 22189267] Codon 72 polymorphism (rs1042522) of TP53 is associated with changes in diastolic blood pressure over time

[PMID 22251423] NAMPT (visfatin) and AKT1 genetic variants associate with myocardial infarction

[PMID 22336942] Investigation of the Effect of MDM2 SNP309 and TP53 Arg72Pro Polymorphisms on the Age of Onset of Cutaneous Melanoma

[PMID 22417303] Infrequent p53 gene mutation but UV gradient-like p53 protein positivity in keloids

[PMID 22294769] Mutations and polymorphisms in TP53 gene--an overview on the role in colorectal cancer.

[PMID 21838531] Crosstalk between the FGFR2 and TP53 genes in breast cancer: data from an association study and epistatic interaction analysis

[PMID 22532853] How Contemporary Human Reproductive Behaviors Influence the Role of Fertility-Related Genes: The Example of the P53 Gene