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Polymorphisms in the CLDN 1 and CLDN 7 genes are related to differentiation and tumor stage in colon carcinoma
Author(s) -
HahnStrömberg Victoria,
Askari Shlear,
Befekadu Rahel,
Matthiessen Peter,
Karlsson Sune,
Nilsson Torbjörn K.
Publication year - 2014
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.12211
Subject(s) - single nucleotide polymorphism , colorectal cancer , genotype , biology , population , cancer , breast cancer , medicine , oncology , pathology , genetics , gene , environmental health
Tight junction is composed of transmembrane proteins important for maintaining cell polarity and regulating ion flow. Among these proteins are the tissue‐specific claudins, proteins that have recently been suggested as tumor markers for several different types of cancer. An altered claudin expression has been observed in colon, prostatic, ovarian, and breast carcinoma. The aim of this study was to analyze the allele frequencies of three common single nucleotide polymorphisms ( SNP s) in the genes for claudin 1 and claudin 7 in colon cancer ( CC ) patients and in a control population of healthy blood donors. Pyrosequencing was used to genotype the CLDN 1 SNP rs9869263 (c.369C>T), and the CLDN 7 SNP s rs4562 (c.590C>T) and rs374400 (c.606T>G) in DNA from 102 formalin fixed paraffin embedded ( FFPE ) colon cancer tissue, and 111 blood leukocyte DNA from blood/plasma donors. These results were correlated with clinical parameters such as TNM stage, tumor localization, tumor differentiation, complexity index, sex, and age. We found that there was a significant association between the CLDN 1 genotype CC in tumor samples and a higher risk of colon cancer development ( OR 3.0, p < 0.001). We also found that the CLDN 7 rs4562 ( c.590C>T) genotype CT had a higher risk of lymph node involvement (p = 0.031) and a lower degree of tumor differentiation (p = 0.028). In the control population, the allele frequencies were very similar to those in the HapMap cohort for CLDN 7 . The CLDN 1 rs9869263 genotype (c.369C>T) was related to increased risk of colon cancer, and the CLDN 7 rs4562 genotype (c.590C>T) was related to tumor differentiation and lymph node involvement in colon carcinoma. Further studies are warranted to ascertain their potential uses as biomarkers predicting tumor development, proliferation, and outcome in this disease.