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. 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, as oriented in dbSNP and to the gene, the less common 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. 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). 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). rs1042522 is not associated with SLE in a study of Caucasians, African-Americans, and Asian children and adults. Implicated in type-2 diabetes based on a study of 1,161 Finnish patients. * rs2279744, rs1042522, rs17878362 and rs1625895 associated with high grade endometrial cancer 23andMe blog 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. 23andMe blog rs1042522(C) might have had an easier time conceiving in colder temperatures 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. 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.

C;C

Chemotherapy is less effective. Accelerated lung decline in smokers. African Americans have 2.15x risk of dying from colo-rectal cancer.