Search

The article reports on the findings of a study of a novel Alu-mediated BRCA1 exon 13 duplication in Chinese breast cancer patients and implications for genetic testing. A description of the experimental setup and measurement methods is given. The multiplex ligation-dependent probe amplification (MLPA) results showed that one patient had a duplication of exon 13 and another had deletion of exon 13. The study concluded the need for pedigree risk assessment for genetic testing.

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 % confidence interval (CI) = 1.26-1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20-1.61) and ER-negative (per-allele OR = 1.55, 95 % CI = 1.28-1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14-1.68), 1.48 (1.25-1.74), and 1.58 (1.28-1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22 (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95 % CI) of 1.16 (1.00-1.34), 1.15 (1.02-1.29), and 1.15 (1.01-1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90 % for those with a combination of 6 or more risk alleles, compared to patients with ≤3 risk alleles.

Background: The incidence of breast carcinoma in Singapore has nearly doubled over the past 25 years. This prospective case-control study involving 1086 women (204 cases and 882 controls) was conducted to determine significant factors associated with the risk of breast carcinoma among Chinese women in Singapore ages 45 to 69 years., Methods: A forward stepwise logistic regression model adjusted for confounding variables of age, age at menarche, menopausal status, parity, age at first and last delivery, use of oral contraceptives, hormone replacement therapy, family history of breast carcinoma, history of benign breast biopsy, smoking history, height, weight, body mass index, and waist to hip ratio was used., Results: Central obesity as indicated by women with a larger waist to hip ratio was associated with highest risk for breast carcinoma (odds ratio [OR]: 9.18; 95% confidence interval [CI],4.8-17.5 comparing last and first quintile; P < 0.0001, chi-square test for trend). Significant trends were also noted for increasing height and breast carcinoma risk (P = 0.003, chi-square test). Women who were taller than 159 cm (OR: 2.3; 95% CI, 1.4-3.9) had approximately twice the risk of women shorter than 150 cm. Body mass index as a measure of generalized obesity did not significantly predict risk for breast carcinoma. Reproductive and menstrual factors significantly related to risk for breast carcinoma were number of deliveries (OR: 0.81; 95% CI, 0.7-0.9; P < 0.001), age at last delivery (P = 0.03), and use of hormone replacement therapy (OR: 0.54; 95% CI, 0.3-0.9; P = 0.01). Previous breast biopsy for benign disease was also associated with a higher risk for breast carcinoma (OR: 3.5; 95% CI, 2.1-5.7; P < 0.001)., Conclusions: The authors conclude that the risk of breast carcinoma is strongly associated with changes in lifestyle related to caloric intake (central obesity and height) and reproductive or menstrual factors (number of deliveries, age at last delivery, age at menopause, and breast feeding). Better and excess nutrition in early and later years of life and fewer births (related to rapid urbanization) may explain in part the increasing incidence of breast carcinoma occurring in Singapore.