Sex-specific effect of the TP53 PIN3 polymorphism on cancer risk in a cohort study of TP53 germline mutation carriers

Germline mutations in the tumor suppressor gene TP53 occur in the majority of families with Li-Fraumeni syndrome, who are at an increased risk for a wide spectrum of early onset cancers. Several genetic polymorphisms in TP53 modify its effect on cancer risk. While some studies indicate that the TP53 PIN3 deletion allele (D) accelerate tumor onset in carriers with TP53 germline mutations, other studies have shown that the TP53 PIN3 insertion allele (I) confers a significantly higher risk of developing cancer than D allele. To further determine the effects of the TP53 PIN3 polymorphism on cancer development among TP53 germline mutations and to evaluate if those are differenence between male and female carriers, we studied a total of 152 germline mutation carriers with available DNA samples that can be used for genotyping. Our results indicate that the TP53 PIN3 polymorphism has a sex-specific effect on the risk of cancer in TP53 mutation carriers, conferring cancer risk in men (P = 0.0041) but not women with DI or II genotypes.