Abstract
The aim of the present study was to determine the changes to the expression levels of fragile histidine triad (FHIT), breast cancer type 2 susceptibility protein (BRCA2), MutL homolog 1 (MLH1) and tumour protein 53 (p53) exhibited by families with a history of oesophageal cancer in a region that has a high incidence of oesophageal cancer, and to determine the association of these changes with the cancer history of the families. Immunohistochemistry was used to detect the protein expression of FHIT, p53, BRCA2, and MLH1 in the excised specimens of cancer tissues from 74 oesophageal cancer patients (positive family history of oesophageal cancer [OCFH +], n=33; negative family history of oesophageal cancer [OCFH −], n=41) from a region with a high incidence of oesophageal cancer. The positive expression rates of FHIT (61%; 45/74), BRCA2 (50%; 37/74) and MLH1 (27%; 9/33) in the oesophageal cancer tissues were significantly lower than those in the healthy tissues adjacent to the cancer (97% [29/30], 87% [26/30] and 73% [25/41], respectively). A significant difference was identified between the positive expression rates (P<0.01). However, FHIT, p53, BRCA2 and MLH1 expression demonstrated no significant affect on clinicopathological changes, such as oesophageal cancerous tissue differentiation, the degree of infiltration and cancer cell metastasis. The FHIT, BRCA2 and MLH1 expression levels were identified to be significantly lower in the cancer tissues from OCFH + patients. This result indicates that the expression levels of FHIT, BRCA2, and MLH1 are important molecular indices of genetic susceptibility to oesophageal cancer.
Highlights
Linzhou is a city in the province of Henan in China, that has the highest oesophageal cancer morbidity and mortality rate in the world [1,2,3]
A descendant of a family with a positive history of oesophageal cancer (OCFH +) tends to have a higher tumour susceptibility when compared with a descendant of a family that has a negative history of oesophageal cancer (OCFH -); the susceptibility increases with the positive family history [5,6,7]
MutL homolog 1 (MLH1) and breast cancer type 2 susceptibility protein (BRCA2) are key genes involved in DNA damage repair, when the damage is induced by foreign carcinogenic factors [11,12]
Summary
Linzhou is a city in the province of Henan in China, that has the highest oesophageal cancer morbidity and mortality rate in the world [1,2,3]. MutL homolog 1 (MLH1) and breast cancer type 2 susceptibility protein (BRCA2) are key genes involved in DNA damage repair, when the damage is induced by foreign carcinogenic factors [11,12] These genes are closely associated with chromosomal stability. The expression of the fragile site genes, FHIT and p53, which are associated with chromosomal stability, were analysed in excised oesophageal cancer tissue specimens, as well as the DNA damage repair genes, BRCA2 and MLH1. The association between these genes and the family history of cancer was determined. The results of the present study may CHANG et al: EXPRESSION ANALYSIS OF SUSCEPTIBILITY GENES IN OESOPHAGEAL CANCER contribute to understanding the molecular mechanism of, and genetic susceptibility of humans to, oesophageal cancer in areas with a high incidence of this type of cancer
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