Estrogen is believed to play a central role in breast cancer development and progression. Blocking the effect of estrogen, either by inhibiting estrogen action or by reducing estrogen production, has been widely used in breast cancer treatment as an adjuvant therapy.¹ Soy foods are rich in phytoestrogens, mainly in the form of isoflavones, which are natural estrogen receptor modulators that possess both estrogen-like and antiestrogenic properties. Soy constituents have also been shown to have other anticancer effects, including the inhibition of DNA topoisomerase I and II, proteases, tyrosine kinases, inositol phosphate, and angiogenesis and may also boost immune response and possess antioxidative effects.^2,3

Xiao-Ou Shu and colleagues report a meta-analysis of genome-wide association studies for body mass index (BMI) in east Asians. They identify three new genetic loci associated with BMI. Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 × 10−8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 × 10−7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations.

Uncertainty exists about the role of dietary carbohydrates in the development of type 2 diabetes mellitus (DM).¹ Several^2-5 but not all studies of primarily white populations have linked dietary glycemic index (GI), an in vivo measure of carbohydrate quality based on the rapidity of its absorption, and glycemic load (GL), a measure of the total glycemic effect of carbohydrates in the diet,^6,7 to an increased risk of type 2 DM. Because bread, potatoes, sugar-sweetened soft drinks, and sweets and desserts are the main sources of dietary GL in Western populations, it has been suggested that the associations between dietary GI and GL and risk of type 2 DM may differ in Chinese and other Asian populations in which rice is the major staple food.⁸

Soy food intake has been shown to have beneficial effects on cardiovascular disease risk factors. Data directly linking soy food intake to clinical outcomes of cardiovascular disease, however, are sparse. We examined the relationship between soy food intake and incidence of coronary heart disease (CHD) among participants in the Shanghai Women's Health Study, a population-based prospective cohort study of ∼75,000 Chinese women aged 40–70 y at the baseline survey that was conducted from 1997 to 2000. Included in this study were 64,915 women without previously diagnosed CHD, stroke, cancer and diabetes at baseline. Information on usual intake of soy foods was obtained at baseline through an in-person interview using a validated food-frequency questionnaire. Cohort members were followed biennially through in-person interviews. After a mean of 2.5 y (162,277 person-years) of follow-up, 62 incident cases of CHD (43 nonfatal myocardial infarctions and 19 CHD deaths) were documented. There was a clear monotonic dose-response relationship between soy food intake and risk of total CHD (P for trend = 0.003) with an adjusted relative risk (RR) of 0.25 (95% CI, 0.10–0.63) observed for women in the highest vs. the lowest quartile of total soy protein intake. The inverse association was more pronounced for nonfatal myocardial infarction (RR = 0.14; 95% CI, 0.04–0.48 for the highest vs. the lowest quartile of intake; P for trend = 0.001). This study provides, for the first time, direct evidence that soy food consumption may reduce the risk of CHD in women.

Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r²<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49×10⁻⁹ (1.15, 1.10–1.20), 1.45×10⁻⁸ (1.13, 1.08–1.18), and 7.14×10⁻⁷ (1.13, 1.08–1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS. Type 2 diabetes, a complex disease affecting more than a billion people worldwide, is believed to be caused by both environmental and genetic factors. Although some studies have shown that certain genes may make some people more susceptible to type 2 diabetes than others, the genes reported to date have only a small effect and account for a small proportion of type 2 diabetes cases. Furthermore, few of these studies have been conducted in Asian populations, although Asians are known to be more susceptible to insulin resistance than people living in Western countries, and incidence of type 2 diabetes has been increasing alarmingly in Asian countries. We conducted a multi-stage study involving 9,794 type 2 diabetes cases and 14,615 controls, predominantly Asians, to discover genes related to susceptibility to type 2 diabetes. We identified 3 genetic regions that are related to increased risk of type 2 diabetes.