Examination of HER-2 SNP 655V gene polymorphism in risk assessment of breast cancer

Konference: 2005 1. ročník Dny diagnostické, prediktivní a experimentální onkologie

Kategorie: Zhoubné nádory prsu

Téma: 01. Predikce účinnosti léčiv směřovaných do EGFR/HER rodiny

Číslo abstraktu: 006

Autoři: Prof. MUDr. Pavol Žúbor, DrSc.; Prof. MUDr. Ján Danko, CSc.; A. Vojvodová; doc. MUDr. Karol Kajo, Ph.D.; N. Szunyogh; Ing. Zuzana Kviatkovská; S. Galo; MUDr. Katarína Macháleková, Ph.D.; K. Biringer; RNDr. Martina Barthová, Ph.D.; C.A. Dussan; Prof. MUDr. Lukáš Plank, CSc.

Breast cancer belongs to the most frequent types of cancer affecting women and it occurs at any age. Around 1600–1800 women are getting ill annually in the Slovak republic. One of the most important factors in connection with cancer genesis refers to changes in specific genes. HER-2 proto-oncogene belongs to low penetrating genes, which increase susceptibility to breast cancer genesis. Clinical studies demonstrated an association between polymorphism at codon 655 of this gene and increased risk for breast cancer development.

The aim of this case-control based prospective study was to determine the distribution of HER-2 genotype and its association with risk factors of breast cancer in the population of Slovak women. HER-2 genotypes were determined with PCR – RFLP method. The DNA was isolated from white blood cell nuclei.

The frequency of Val allele in the cancer group was 29.51 % and was higher than in the control group 15.49 % (p < 0.05). The presence of the heterozygote (Ile/Val) genotype was identified in 45.90 % of patients in the case group and in 28.17 % in healthy individuals, and the homozygote (Val/Val) genotype in 6.56 % and 1.41 %, respectively (p < 0.001). The risk of breast cancer development for carriers of one valine (Val) allele in genotype was nearly three-times lower (OR = 2.41) than for carriers of two Val alleles (OR = 6.89) (p < 0.01). Risk of cancer genesis for Val allele carriers was higher in multiparas (OR = 2.78), among women with positive family history of breast cancer (OR = 5.4), BMI > 24 (kg/m2) (OR = 5.8), late menopause (OR = 1.6), and early onset of menarche (OR = 1.2).
This study revealed relatively high frequency of the Val allele among the Slovak women population. Ile655Val polymorphism of HER-2 gene was associated with a statistically significantly increased risk of breast cancer all above in homozygotes for Val allele.

Acknowledgements: We would like to express our gratitude to the patients participated in this study. This work was supported by grant of Comenius University no. 22/2004.

Datum přednesení příspěvku: 9. 12. 2005