HVEM Gene Polymorphisms Are Associated with Sporadic Breast Cancer in Chinese Women

<div><p>As a costimulatory molecule, Herpesvirus entry mediator (HVEM) can bind with several costimulatory members, thus HVEM plays different roles in T cell immunity. HVEM and its ligands have been involved in the pathogenesis of various autoimmune, inflammatory diseases and tumors. In the current study, we conducted a case-control study comparing polymorphisms of HVEM and breast cancer. Subjects included 575 females with breast cancer and 604 age-matched healthy controls. Six HVEM SNPs (rs2281852, rs1886730, rs2234163, rs11573979, rs2234165, and rs2234167) were genotyped by PCR-RFLP. The results showed significant differences in genotypes and alleles between rs1886730 and rs2234167 (<i>P</i><0.05). One haplotype (CTGCGG) that was associated with breast cancer was found via haplotype analysis. Our research also indicated an association between polymorphisms of HVEM and clinicopathologic features, including lymph node metastasis, estrogen receptor, progesterone receptor and P53. Our results primarily indicate that polymorphisms of the HVEM gene were associated with the risk of sporadic breast cancer in northeast Chinese females.</p></div

Primers and PCR programs for HVEM PCR-RFLP genotyping.

<p>Primers and PCR programs for HVEM PCR-RFLP genotyping.</p

Haplotypes of HVEM gene.

<p>S1 = rs2281852, S2 = rs1886730, S3 = rs2234163, S4 = rs11573979, S5 = rs2234165, S6 = rs2234167.</p>*<p>correcting the P value for multiple testing by Haploview program using 10,000 permutations.</p

Clinicopathologic information of breast cancer patients.

<p>IDC infiltrative ductal carcinoma, MC medullary carcinoma, LN lymph node, TZ tumor size, ER estrogen receptor, PR progesterone receptor.</p

Allele frequencies of HVEM polymorphisms and their associations with breast cancer risk.

*<p>P<0.01 after correcting the P value for multiple testing by Haploview program using 10,000 permutations.</p><p>Rs2281852: cases n = 575, missing n = 0; controls n = 604, missing n = 0.</p><p>Rs1886730: cases n = 564, missing n = 11; controls n = 600, missing n = 4.</p><p>Rs2234163: cases n = 570, missing n = 5; controls n = 602, missing n = 2.</p><p>Rs11573979: cases n = 571, missing n = 4; controls n = 601, missing n = 3.</p><p>Rs2234165: cases n = 574, missing n = 1; controls n = 601, missing n = 3.</p><p>Rs2234167: cases n = 574, missing n = 1; controls n = 603, missing n = 1.</p