Association of a single nucleotide polymorphism at 6q25.1, rs2046210, with endometrial cancer risk among Chinese women

A recent genome-wide association study identified a new susceptibility locus for breast cancer, rs2046210, which is a single nucleotide polymorphism (SNP) located upstream of the estrogen receptor α (ESR1) gene on chromosome 6q25.1. Given that endometrial cancer shares many risk factors with breast cancer and both are related to estrogen exposure and that rs2046210 is in close proximity to the ESR1 gene, we evaluated the association of SNP rs2046210 with endometrial cancer risk among 953 cases and 947 controls in a population-based, case-control study conducted in Shanghai, China. Logistic regression models were used to derive odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjusting for potential confounders. We found that the A allele of rs2046210, linked to an increased risk of breast cancer, was associated with increased but not statistically significant risk of endometrial cancer (OR = 1.16, 95% CI = 0.96-1.41 for the GA and AA genotypes compared with the GG genotype); the association was stronger among post-menopausal women (OR = 1.28, 95% CI = 1.00-1.65). The association tended to be stronger among women with higher or longer estrogen exposure than among women with relatively lower or shorter exposure to estrogen. Our study suggests that rs2046210 may play a role in the etiology of endometrial cancer. Additional studies are needed to confirm our findings.

Role of TGF-β1 and its Receptors in Breast Carcinogenesis:Evaluation of Gene Expression Patterns and Clinical Implications

OBJECTIVE Transforming growth factor β1 （TGF-β1） is a multifunc- tional cytokine that may play an important role in tumor development and progression. METHODS We evaluated gene expression patterns of TGF-β1 and its receptors [transforming growth factor β type Ⅰ receptor （TβR- Ⅰ ） and transforming growth factor β type Ⅱ receptor （TβR- Ⅱ ）] in tumor tissue from patients with breast cancer or with benign breast diseases （BBD） and adjacent normal tissue from the patients with breast cancer. Included in the study were 527 breast cancer patients and 213 BBD patients who participated in the Shanghai Breast Cancer Study. RESULTS The expression levels of the TGF-β1, TβR- Ⅰ and TβR-Ⅱ genes in breast tissue were quantified using real-time PCR. TIER- Ⅱ expression in cancer tissue was decreased by over 50% as compared to either adjacent normal tissue from the same patients or benign tumor tissue from BBD patients （p〈0.001）. TGF-β1 expression was lower by approximately 20% in cancer tissue compared to adjacent normal tissue （p=0.14） or to benign tumor tissue （p=0.002）. Although TβR-Ⅰ expression was also reduced in cancer tissue compared to adjacent normal tissue, or benign tumor tissue, the magnitude of the reduction was less apparent than that for TβR- Ⅱ. Compared to patients with the lowest tertile value for TβR- Ⅱ, patients with median tertile value for TβR- Ⅱ had more favorable overall survival （HR 0.47, 95% CI 0.27-0.85） and disease-free survival （HR 0.65, 95% CI 0.39-1.06）. No apparent associations, however, were observed between TGF-β1 or TβR- Ⅰ expression and overall or disease-free survival. CONCLUSION The results from this study support the hypothesis that a decreased level of TβR-Ⅱ gene expression, and thus reduced TGF-β1 sensitivity, is related to breast tumor progression.

Very Low-Level Heteroplasmy mtDNA Variations Are Inherited in Humans

Little is known about the inheritance of very low heteroplasmy mitochondria DNA （mtDNA） variations. Even with the development of new next-generation sequencing methods, the practical lower limit of measured heteroplasmy is still about 1% due to the inherent noise level of the sequencing. In this study, we sequenced the mitochondrial genome of 44 individuals using Illumina high-throughput sequencing technology and obtained high-coverage mitochondria sequencing data. Our study population contains many mother-offspring pairs. This unique study design allows us to bypass the usual heteroplasmy limitation by analyzing the correlation of mutation levels at each position in the mtDNA sequence between maternally related pairs and non-related pairs. The study showed that very low heteroplasmy variants, down to almost 0.1%, are inherited maternally and that this inheritance begins to decrease at about 0.5%, cor- resnondin to abottleneck of about 200 mtDNA.