Kallikrein gene variants modulate OSCC development

Mar 1 2013

By Joanna Lyford, Senior medwireNews Reporter

Polymorphisms in the kallikrein7 (KLK7) and kallikrein10 (KLK10) genes are associated with the development and progression of oral squamous cell carcinoma (OSCC), a study in Taiwanese men indicates.

The study involved 217 men with OSCC. All were of Minnan ethnicity, smoked cigarettes, and chewed betel quid. A further 138 healthy men served as controls.

"Data suggest that kallikreins are involved with the development and progression of oral cancer, especially in betel quid chewers," note Tien-Yu Shieh (Kaohsiung Medical University, Taiwan) and co-authors.

All participants were genotyped for rs10581213 in the KLK7 gene and rs3745535 in KLK10.

Results, published in Oral Diseases, showed that the KLK10 rs3745535G>T polymorphism was significantly associated with risk for OSCC, with an odds ratio of 1.62 versus wild-type after adjustment for age, education, and alcohol consumption.

None of the KLK7 polymorphisms were associated with OSCC risk. However, the KLK7 rs10581213(wt/ins + ins/ins) genotypes were significantly associated with early-stage cancer (stage I/II) in patients with OSCC, with an adjusted odds ratio of 0.34 versus wild-type.

In a separate analysis of 20 paired tissue samples, levels of both KLK7 mRNA and KLK10 mRNA were significantly higher in cancerous than in healthy tissue.

Also, KLK7 mRNA expression was significantly higher in samples of early-stage cancer with the rs10581213(wt/ins + ins/ins) genotypes, whereas mRNA levels of either protein were similar in early versus late-stage cancers.

Taken together, the results indicate that KLK10 rs3745535G>T polymorphisms are associated with the development of OSCC but not with advanced-stage cancer. Meanwhile, the KLK7 rs10581213(wt/ins + ins/ins) genotypes are associated with early-stage cancer but not with the development of OSCC.

"Higher KLK7 expression is associated with the rs10581213(wt/ins + ins/ins) genotypes in early-stage cancer, and the biological behaviors of KLK7 partially explain this clinical observation," Shieh and co-authors conclude.

"More studies to verify our findings and explore the mechanisms are needed."

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