Prostate Stem Cell Antigen Single Nucleotide Polymorphisms Influence Risk of Estrogen Receptor Negative Breast Cancer in Korean Females

Abstract

Introduction: Breast cancer is the second leading cancer in Korean women. To assess potential genetic associations between the prostate stem cell antigen (PSCA) gene in the chromosome 8q24 locus and breast cancer risk in Korean women, 13 SNPs were selected and associations with breast cancer risk were analyzed with reference to hormone receptor (HR) and menopausal status. Methods:We analyzed DNA extracted from buffy coat from 456 patients and 461 control samples, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) based upon region-specific PCR followed by allelespecific single base primer extension reactions. Risks associated with PSCA genotypes and haplotypes were estimated with chi-square test (χ 2 -test), and polytomous logistic regression models using odds ratios (OR) and 95% confidence intervals (CIs), by HR and menopausal status. Results: In case-control analysis, odds ratios (OR) of rs2294009, rs2294008, rs2978981, rs2920298, rs2976395, and rs2976396 were statistically significant only among women with estrogen receptor (ER) negative cancers, and those of rs2294008, rs2978981, rs2294010, rs2920298, rs2976394, rs10216533, and rs2976396 were statistically significant only in pre-menopausal women, and not in postmenopausal women. Risk with the TTGGCAA haplotype was significantly elevated in ER (-) status (OR= 1.48, 95% CI= 1.03~2.12, p<0.05). Especially risk of allele T of rs2294008 is significantly low in pre-menopausal breast cancer patients and AA genotype of rs2976395 in ER (-) status represents the increase of OR value. Conclusion: This report indicated for the first time that associations exist between PSCA SNPs and breast cancer susceptibility in Korean women, particularly those who are pre-menopausal with an estrogen receptor negative tumor status.

PSCA s2294008 C>T and rs2976392 G>A polymorphisms contribute to cancer susceptibility: evidence from published studies

“…Overall, there were 32 studies investigating the association between PSCA rs2294008 C>T polymorphism and cancer susceptibility, consisting of 30028 cases and 38765 controls [8, 9, 14-35, 39-43], and 14 studies performed on the relation between PSCA rs2976392 G>A polymorphism and overall cancer susceptibility, with 8190 cases and 7176 controls [8, 14-17, 19, 24, 29, 36-39, 43]. The main characteristics of the studies included in this meta-analysis were summarized in Table 1.…”

“…The studied cancer type included gastric cancer [8, 14-17, 20-22, 25, 26, 31, 32, 34, 39, 41-43], bladder cancer [9, 18, 23, 28, 35, 40], prostate cancer [19], esophageal cancer [20, 33], breast cancer [24], colorectal cancer [27], and gallbladder cancer [29, 30]. In term of ethnicity, 21 studies were performed among Asians, 10 studies among Caucasians, and one study among Africans.…”

“…For the PSCA rs2976392 G>A polymorphism, the number of cases ranged from 44 to 1525 while varying control sample sizes (from 60 to 1397) were also observed among selected studies. The studied cancer type included gastric cancer [8, 14-17, 36-39, 43], prostate cancer [19], breast cancer [24], and gallbladder cancer [29]. Of them, 13 studies were performed among Asians and one among Caucasians.…”

PSCA gene variants (rs2294008 and rs2978974) confer increased susceptibility of gallbladder carcinoma in females

“…They suggested that since the PSCA may have significantly higher expression levels in males than in females, decrease in PSCA expression levels due to the SNPs in PSCA would have more significant impact on the function of this tumor suppressor in females than in males (Wu et al, 2009a). Another study showed a significant association between PSCA SNPs and breast cancer susceptibility in Korean women, particularly those who were pre-menopausal with an estrogen receptor negative tumor status (Kim et al, 2012).…”

“…PSCA, involving either change in protein expression or through association with the polymorphism in the PSCA gene, may act as an oncogene; play a role in tumor progression in some cancers while tumor suppressor gene in others (Saeki et al, 2010;Smith et al, 2012). Genetic variants of PSCA have been found to be strongly associated with the risk for cancers of the breast (Kim et al, 2012), bladder (Rothman et al, 2010), duodenal (Tanikawa et al, 2012) and stomach (Qiao and Feng, 2012) etc. Recently, PSCA has been shown to be involved in GBC development (Ono et al, 2012) and its SNP rs2294008, is also considered a potential genetic risk factor in GBC.…”