Effects of reproductive and demographic changes on breast cancer incidence in China: A modeling analysis

Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
CancerSpectrum Knowledge Environment (Impact Factor: 15.16). 10/2008; 100(19):1352-60. DOI: 10.1093/jnci/djn305
Source: PubMed

ABSTRACT Breast cancer incidence is currently low in China. However, the distribution of reproductive and lifestyle risk factors for breast cancer among Chinese women is changing rapidly. We quantified the expected effect of changes in breast cancer risk factors on future rates of breast cancer in China.
We first validated and calibrated the Rosner-Colditz log-incidence breast cancer model in Chinese women who participated in the Shanghai Women's Health Study cohort (N = 74,942). We then applied the calibrated model to a representative sample of Chinese women who were aged 35-49 years in 2001 using data from the Chinese National Family Planning and Reproductive Health Survey (NFPRHS, N = 17,078) to predict the age-specific and cumulative breast cancer incidence among all Chinese women of this age group. We evaluated the relative impact of changes in modifiable risk factors, including alcohol intake, parity, postmenopausal hormone use, and adult weight gain, on cumulative incidence of breast cancer.
Breast cancer incidence in China is expected to increase substantially from current rates, estimated at 10-60 cases per 100,000 women, to more than 100 new cases per 100,000 women aged 55-69 years by 2021. We predicted 2.5 million cases of breast cancer by 2021 among Chinese women who were 35-49 years old in 2001. Modest reductions in hormone and alcohol use, and weight maintenance could prevent 270,000 of these cases.
China is on the cusp of a breast cancer epidemic. Although some risk factors associated with economic development are largely unavoidable, the substantial predicted increase in new cases of breast cancer calls for urgent incorporation of this disease in future health care infrastructure planning.

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    ABSTRACT: Objective To provide an overview of the incidence and mortality of female breast cancer for countries in the Asia-Pacific region. Methods Statistical information about breast cancer was obtained from publicly available cancer registry and mortality databases (such as GLOBOCAN), and supplemented with data requested from individual cancer registries. Rates were directly age-standardised to the Segi World Standard population and trends were analysed using joinpoint models. Results Breast cancer was the most common type of cancer among females in the region, accounting for 18% of all cases in 2012, and was the fourth most common cause of cancer-related deaths (9%). Although incidence rates remain much higher in New Zealand and Australia, rapid rises in recent years were observed in several Asian countries. Large increases in breast cancer mortality rates also occurred in many areas, particularly Malaysia and Thailand, in contrast to stabilising trends in Hong Kong and Singapore, while decreases have been recorded in Australia and New Zealand. Mortality trends tended to be more favourable for women aged under 50 compared to those who were 50 years or older. Conclusion It is anticipated that incidence rates of breast cancer in developing countries throughout the Asia-Pacific region will continue to increase. Early detection and access to optimal treatment are the keys to reducing breast cancer-related mortality, but cultural and economic obstacles persist. Consequently, the challenge is to customise breast cancer control initiatives to the particular needs of each country to ensure the best possible outcomes.
    06/2014; 11(2):101-15. DOI:10.7497/j.issn.2095-3941.2014.02.005
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    ABSTRACT: Angiogenesis plays a crucial role in the growth, invasion and metastasis of breast cancer. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are the key regulators of tumor angiogenesis. VEGFR-2, known as the kinase insert domain receptor (KDR), is a key receptor involved in malignant angiogenesis. We previously showed that knocking down KDR with short interference RNA (KDR-siRNA) markedly decreased KDR expression and suppressed tumor growth in a xenograft model. However, the mechanisms underlying the anti-cancer effects of KDR-siRNA are not clearly understood. This study aimed to elucidate the molecular mechanisms that induce apoptosis in human breast cancer MCF-7 cells after transfection with KDR-siRNA. We studied the effects of KDR-siRNA on proliferation, apoptosis, antiapoptotic and pro-apoptotic proteins, mitochondrial membrane permeability, cytochrome c release and caspase-3 activity. The results indicated that KDR-siRNA treatment significantly inhibited the proliferation and induced the apoptosis of MCF-7 cells, reduced the levels of the anti-apoptotic proteins, Bcl-2 and Bcl-xl, and increased the level of the pro-apoptotic protein Bax, resulting in a decreased Bcl-2/Bax ratio. KDR-siRNA also enhanced the mitochondrial membrane permeability, induced cytochrome c release from the mitochondria, upregulated apoptotic protease-activating factor-1 (Apaf-1), cleaved caspase-3, and increased caspase-3 activity in MCF-7 cells. Furthermore, KDR-siRNA-induced apoptosis in MCF-7 cells was blocked by the caspase inhibitor Z-VAD-FMK, suggesting a role of caspase activation in the induction of apoptosis. These results indicate that the Bcl-2 family proteins and caspase-related mitochondrial pathways are primarily involved in KDR-siRNAinduced apoptosis in MCF-7 cells and that KDR might be a potential therapeutic target for human breast cancer treatments.
    Cellular & Molecular Biology Letters 09/2014; 19(4). DOI:10.2478/s11658-014-0210-8 · 1.78 Impact Factor
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    ABSTRACT: IntroductionSeveral genome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) at 6q25.1 that are associated with breast cancer susceptibility. However, the exact causal variant(s) in this region has not been clarified.Methods In the present study, we genotyped six potentially functional SNPs within CCDC170 and ESR1 gene regions at 6q25.1 and accessed their associations with risk of breast cancer in a study of 1,064 cases and 1,073 cancer-free controls in Chinese women. Biological function of the risk variant was further evaluated by laboratory experiments.ResultsBreast cancer risk was significantly associated with three SNPs located at 6q25.1: rs9383935 in CCDC170 and rs2228480 and rs3798758 in ESR1, with variant-allele attributed odds ratio (OR) of 1.38 (95% confidence interval (CI): 1.20 - 1.57, P¿=¿2.21¿×¿10¿6), 0.84 (95% CI: 0.72 - 0.98, P¿=¿0.025) and 1.19 (95% CI: 1.04-1.37, P¿=¿0.013), respectively. The functional variant rs9383935 is in high linkage disequilibrium (LD) with GWAS-reported top-hit SNP (rs2046210), but only rs9383935 showed a strong independent effect in conditional regression analysis. The rs9383935 risk allele A showed a decreased activity of reporter gene in both MCF-7 and BT-474 breast cancer cell lines, which might be due to an altered binding capacity of miR-27a to the 3¿untranslated region (3¿UTR) sequence of CCDC170. Real-time quantitative reverse transcription PCR confirmed the correlation between rs9383935 genotypes and CCDC170 expression levels.Conclusions This study suggests that the functional variant rs9383935, located at the 3¿UTR of CCDC170, may be one candidate of the causal variants at 6q25.1 that modulate risk of breast cancer.
    Breast cancer research: BCR 08/2014; 16(4):422. DOI:10.1186/s13058-014-0422-x · 5.88 Impact Factor

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