Ping Cui1, Yanrui Zhao1, Xinlei Chu1, Na He2, Hong Zheng1, Jiali Han3, Fengju Song4, Kexin Chen5. 1. Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy in Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China. 2. Department of Cancer Biobank, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, National Clinical Research Centre of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China. 3. Department of Epidemiology, Fairbanks School of Public Health, Indiana University Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA. 4. Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy in Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China. songfengju@163.com. 5. Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy in Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China. chenkexin1963@yahoo.com.
Abstract
PURPOSE: An increasing number of long intergenic non-coding RNAs (lincRNAs) appear to play critical roles in cancer development and progression. To assess the association between SNPs that reside in regions of lincRNAs and breast cancer risk, we performed a large case-control study in China. METHODS: We carried out a two-stage case-control study including 2881 breast cancer cases and 3220 controls. In stage I, we genotyped 17 independent (r2 < 0.5) SNPs located in 6 tumor-related lincRNAs by using the TaqMan platform. In stage II, SNPs potentially associated with breast cancer risk were replicated in an independent population. Quantitative real-time PCR was used to measure H19 levels in tissues from 228 breast cancer patients with different genotypes. RESULTS: We identified 2 SNPs significantly associated with breast cancer risk in stage I (P < 0.05), but not significantly replicated in stage II. We combined the data from stage I and stage II, and found that, compared with the rs2071095 CC genotype, AA and CA + AA genotypes were associated with significantly decreased risk of breast cancer (adjusted OR 0.83, 95% CI 0.69-0.99; adjusted OR 0.88, 95% CI 0.80-0.98, respectively). Stratified analyses showed that rs2071095 was associated with breast cancer risk in estrogen receptor (ER)-positive patients (P = 0.002), but not in ER-negative ones (P = 0.332). Expression levels of H19 in breast cancer cases with AA genotype were significantly lower than those with CC genotype. CONCLUSIONS: We identified that rs2071095 may contribute to the susceptibility of breast cancer in Chinese women via affecting H19 expression. The mechanisms underlying the association remain to be investigated.
PURPOSE: An increasing number of long intergenic non-coding RNAs (lincRNAs) appear to play critical roles in cancer development and progression. To assess the association between SNPs that reside in regions of lincRNAs and breast cancer risk, we performed a large case-control study in China. METHODS: We carried out a two-stage case-control study including 2881 breast cancer cases and 3220 controls. In stage I, we genotyped 17 independent (r2 < 0.5) SNPs located in 6 tumor-related lincRNAs by using the TaqMan platform. In stage II, SNPs potentially associated with breast cancer risk were replicated in an independent population. Quantitative real-time PCR was used to measure H19 levels in tissues from 228 breast cancerpatients with different genotypes. RESULTS: We identified 2 SNPs significantly associated with breast cancer risk in stage I (P < 0.05), but not significantly replicated in stage II. We combined the data from stage I and stage II, and found that, compared with the rs2071095 CC genotype, AA and CA + AA genotypes were associated with significantly decreased risk of breast cancer (adjusted OR 0.83, 95% CI 0.69-0.99; adjusted OR 0.88, 95% CI 0.80-0.98, respectively). Stratified analyses showed that rs2071095 was associated with breast cancer risk in estrogen receptor (ER)-positive patients (P = 0.002), but not in ER-negative ones (P = 0.332). Expression levels of H19 in breast cancer cases with AA genotype were significantly lower than those with CC genotype. CONCLUSIONS: We identified that rs2071095 may contribute to the susceptibility of breast cancer in Chinese women via affecting H19 expression. The mechanisms underlying the association remain to be investigated.
Entities:
Keywords:
Breast cancer; Genetic susceptibility; H19; LincRNA; SNP
Authors: Maija Suvanto; Jonathan Beesley; Carl Blomqvist; Georgia Chenevix-Trench; Sofia Khan; Heli Nevanlinna Journal: Front Genet Date: 2020-06-30 Impact factor: 4.599