목적: 자궁내막암 환자를 대상으로 정상 대조군과 비교하여 연령에 따라 HER-2 유전자의 다형성 (polymorphisms)의 분포가 자궁내막암 위험도와 관련이 있는지 분석하고 자궁내막암의 병리학적인 특성과의 상관관계를 분석하고자 한다. 연구 방법: 조직학적으로 증명된 125명의 자궁내막암 환자와 302명의 정상 대조군을 대상으로 4가지 HER-2 SNPs [SNP1 (I655V) - rs1801200, SNP2 - rs1810132, SNP3 - rs2517951, SNP4 (P1170A) - rs1058808]을 분석하였다. 각각 파라핀 조직으로부터 DNA를 추출하여 GenomeLab SNPstream (Ultra-high throughput; UHT system)을 이용하여 유전자형을 분석하였다. 신체질량지수 (BMI)에 대한 보정을 마친 후 교차비 (odd ratio)와 95% 신뢰구간 (confidence intervals; CIs)을 추정하기 위해 무조건의 회귀분석 (unconditional logistic regression)을 이용하였다. 결과: 자궁내막암 발생과 HER-2 유전자 다형성 및 나이와는 통계적으로 의미 있는 차이를 발견할 수 없었다. 그러나, 50세 이하에서 SNP1 (I655V) GA/GG 유전자 형을 갖는 환자가 SNP1 AA 유전자 형을 갖는 환자에 비해 진행된 병기 이거나 분화도가 높을 확률이 더 낮은 것을 관찰할 수 있었고 (adjusted OR= 0.59, 95% CI 0.10~3.69). 50세 이상 환자에서 SNP1 GA/GG 유전자 형을 갖는 경우 진행된 병기이거나 분화도가 높을 확률이 2.17배 (CI 0.65~7.27) 증가하는 것을 관찰할 수 있었다. SNP 4 (P1170A)역시 SNP1과 비슷한 결과를 보였다. 그러나, 두 SNP 모두 통계적 유의성은 관찰할 수 없었다. 결론: 자궁내막암의 발생과 HER-2 유전자형 및 나이와의 상관관계에서 통계적으로 유의한 결과를 확인할 수는 없었다. 본 연구는 통계적 유의성을 획득하기에는 환자수가 적은 제한점을 갖는다. 따라서 향후 더 큰 규모의 대상자에서 연구가 필요할 것으로 생각되며, 이에 더불어 유전적인 요인에 대한 추가적인 연구가 필요할 것으로 생각된다.

Objective: To evaluate the relationship between single nucleotide polymorphisms (SNPs) in the HER-2 gene and age on the risk and pathologic feature of endometrial cancer. Methods: We included 125 women with histologically confirmed endometrioid adenocarcinoma who underwent complete surgical staging. The control group consisted of 302 patients with benign gynecologic disease who underwent hysterectomy. Nine SNPs spanning the HER-2 gene were genotyped by SNP-IT assay using SNPstream® Genotyping System. Of 9 SNPs, 5 that were either monomorphic or had a low allele frequency (<10%) in this population were removed, leaving 4 SNPs (SNP1- rs1801200, SNP2- rs1810132, SNP3- rs2517951, SNP4- rs1058808) with allele frequencies ≥10%; these were included in the final analysis. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for BMI. Results: The mean age for endometrial cancer patients was 53.4±11.5 (range, 29-81) years. Forty-seven patients (38%) were <50 years of age, and 78 patients (62%) were ≥50 years. Cases had a significantly higher BMI than controls (P<0.001). After adjustment for BMI, there was no significant relationship between HER-2 polymorphism and the risk of endometrial cancer based on age. Furthermore, HER-2 polymorphism did not affect the pathologic features of endometrial cancer based on age. Conclusion: Although there is no potential association among HER-2 polymorphisms, age, and endometrial cancer risk, large studies are needed in the future to assess the role of this polymorphism in endometrial cancer and for its combined effect.

Objective: To evaluate the relationship between single nucleotide polymorphisms (SNPs) in the HER-2 gene and age on the risk and pathologic feature of endometrial cancer. Methods: We included 125 women with histologically confirmed endometrioid adenocarcinoma who underwent complete surgical staging. The control group consisted of 302 patients with benign gynecologic disease who underwent hysterectomy. Nine SNPs spanning the HER-2 gene were genotyped by SNP-IT assay using SNPstream® Genotyping System. Of 9 SNPs, 5 that were either monomorphic or had a low allele frequency (<10%) in this population were removed, leaving 4 SNPs (SNP1- rs1801200, SNP2- rs1810132, SNP3- rs2517951, SNP4- rs1058808) with allele frequencies ≥10%; these were included in the final analysis. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for BMI. Results: The mean age for endometrial cancer patients was 53.4±11.5 (range, 29-81) years. Forty-seven patients (38%) were <50 years of age, and 78 patients (62%) were ≥50 years. Cases had a significantly higher BMI than controls (P<0.001). After adjustment for BMI, there was no significant relationship between HER-2 polymorphism and the risk of endometrial cancer based on age. Furthermore, HER-2 polymorphism did not affect the pathologic features of endometrial cancer based on age. Conclusion: Although there is no potential association among HER-2 polymorphisms, age, and endometrial cancer risk, large studies are needed in the future to assess the role of this polymorphism in endometrial cancer and for its combined effect.

Age, HER-2, Single nucleotide polymorphism, Endometrial cancer