Common Genetic Variation at PTEN and Risk of Sporadic Breast and Prostate Cancer

Abstract

PTEN frequently shows loss of heterozygosity in breast and prostate cancers, and mutations in this gene are responsible for Cowden disease, a rare Mendelian syndrome that includes breast cancer as part of its phenotype. Thus, PTEN serves as a candidate susceptibility gene for both breast and prostate cancer risk. Whether common inherited variation (either coding or noncoding) at the PTEN locus contribute to nonfamilial, sporadic breast and prostate cancer risk is not known. In this study, we employed a linkage disequilibrium -based approach to test for association between common genetic variation at the PTEN locus and breast and prostate cancer risk in African-American, Native Hawaiian, Japanese, Latina, and White men and women in the Multiethnic Cohort Study. We genotyped 17 common single nucleotide polymorphisms (SNP; z5% frequency in at least one ethnic group) spanning the PTEN gene to define the common alleles in these populations.These SNPs were in strong linkage disequilibrium, indicating that our survey captured most of the common sequence variation across this locus. Eight tagging SNPs were selected to predict the common PTEN haplotypes (z0.05 frequency) in these populations (two additional tagging SNPs were required for African Americans). These SNPs were evaluated in a breast cancer case-control study (cases, n = 1,615; controls, n = 1,962) and prostate cancer case-control study (cases, n = 2,320; controls, n = 2,290) nested within the Multiethnic Cohort Study. Multiple testing was explicitly accounted for by applying a permutation-based framework. We found no strong association with any common haplotype in relation to breast or prostate cancer risk. In summary, our results show that common variants in PTEN do not substantially influence risk of these two common cancers.

Rituximab inhibits the constitutively activated PI3K-Akt pathway in B-NHL cell lines: involvement in chemosensitization to drug-induced apoptosis

“…Targeting of Akt, directly or indirectly, inhibits cell proliferation, promotes apoptosis and/or increases sensitivity to chemotherapy (Tachiiri et al, 2000). The loss of PTEN expression has been reported in a variety of cancers (Rennie and Nelson, 1998;Marsit et al, 2005;Haiman et al, 2006). There are relatively a few studies exploring PTEN abnormalities in lymphoma.…”

No association between phosphatase and tensin homolog genetic polymorphisms and colon cancer

“…Taken together with other studies [18][19][20] , our results do not support PTEN as a colon cancer susceptibility gene.…”

“…In addition, PTEN missense and nonsense mutations occur in Cowden Disease, a hereditary cancer susceptibility syndrome involving multiple hamartomas of the gastrointestinal tract and other tissues [16,17] . To date, three published studies have examined PTEN as a potential candidate susceptibility gene for four cancer types: breast and prostate cancer [18] , meningiomas [19] , and colorectal cancer [20] . These studies found no association with PTEN genetic polymorphisms.…”

Screening of PTEN Gene Mutations in Gastric Cancer

“…Ha i man et al in ves tiga ted the re la ti o of rs1903858 with bre ast and pros ta te can cer risks in the ir mul ti eth nic po pu la ti on study, and they co uld not find any re la ti ons. 33 Si milarly, Tre o lar et al re por ted that the re was no as soci a ti on bet we en SNP in PTEN and ma lig nant trans for ma ti on of en do met ri o sis for ma ti on. 34 In the sa me way, Song et al in ves ti ga ted the ge ne tic as soci a ti on bet we en rs1903858 and lary ngo car ci no ma in Chi ne se Han po pu la ti on, but they co uld not find any as so ci a ti on of the SNP with lary ngo car ci no ma in this po pu la ti on.…”