Bu-Tian Ji

Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women's Health Study

BACKGROUND Soy food is a rich source of isoflavones--a class of phytoestrogens that has both antiestrogenic and anticarcinogenic properties. OBJECTIVE The objective was to evaluate the association of adolescent and adult soy food intake with breast cancer risk in a cohort of 73,223 Chinese women who participated in the Shanghai Womens Health Study. DESIGN A validated food-frequency questionnaire was used to assess usual dietary intake during adulthood and adolescence. After a mean follow-up of 7.4 y, 592 incident cases of breast cancer were identified for longitudinal analyses by using Cox regressions. RESULTS Adult soy food consumption, measured either by soy protein or isoflavone intake, was inversely associated with the risk of premenopausal breast cancer, and the association was highly statistically significant (P for trend < 0.001). The multivariate-adjusted relative risks (RRs) for the upper intake quintile compared with the lowest quintile were 0.41 (95% CI: 0.25, 0.70) for soy protein intake and 0.44 (95% CI: 0.26, 0.73) for isoflavone intake. High intake of soy foods during adolescence was also associated with a reduced risk of premenopausal breast cancer (RR: 0.57; 95% CI: 0.34, 0.97). Women who consumed a high amount of soy foods consistently during adolescence and adulthood had a substantially reduced risk of breast cancer. No significant association with soy food consumption was found for postmenopausal breast cancer. CONCLUSION This large, population-based, prospective cohort study provides strong evidence of a protective effect of soy food intake against premenopausal breast cancer.

Dietary habits and stomach cancer in Shanghai, China

Stomach cancer remains the second leading cancer in incidence in Shanghai, China, despite its decline over the past 2 decades. To clarify risk factors for this common malignancy, we conducted a population‐based case‐control study in Shanghai, China. Included in the study were 1,124 stomach cancer patients (age 20–69) newly diagnosed in 1988–1989 and 1,451 controls randomly selected among Shanghai residents. Usual adult dietary intake was assessed using a comprehensive food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Risks of stomach cancer were inversely associated with high consumption of several food groups, including fresh vegetables and fruits, poultry, eggs, plant oil, and some nutrients, such as protein, fat, fiber and antioxidant vitamins. By contrast, risks increased with increasing consumption of dietary carbohydrates, with odds ratios (ORs) of 1.5 (95% confidence interval [CI] 1.1–2.1) and 1.9 (95% CI 1.3–2.9) in the highest quartile of intake among men (p for trend = 0.02) and women (p = 0.0007), respectively. Similar increases in risk were associated with frequent intake of noodles and bread in both men (p = 0.07) and women (p = 0.05) after further adjustment for fiber consumption. In addition, elevated risks were associated with frequent consumption of preserved, salty or fried foods, and hot soup/porridge, and with irregular meals, speed eating and binge eating. No major differences in risk were seen according to subsite (cardia vs. non‐cardia). Our findings add to the evidence that diet plays a major role in stomach cancer risk and suggest the need for further evaluation of risks associated with carbohydrates and starchy foods as well as the mechanisms involved. Int. J. Cancer 76:659–664, 1998. Published 1998 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.

Genome-wide association analyses in east Asians identify new susceptibility loci for colorectal cancer

To identify new genetic factors for colorectal cancer (CRC), we conducted a genome-wide association study in east Asians. By analyzing genome-wide data in 2,098 cases and 5,749 controls, we selected 64 promising SNPs for replication in an independent set of samples, including up to 5,358 cases and 5,922 controls. We identified four SNPs with association P values of 8.58 × 10−7 to 3.77 × 10−10 in the combined analysis of all east Asian samples. Three of the four were replicated in a study conducted in 26,060 individuals of European descent, with combined P values of 1.22 × 10−10 for rs647161 (5q31.1), 6.64 × 10−9 for rs2423279 (20p12.3) and 3.06 × 10−8 for rs10774214 (12p13.32 near the CCND2 gene), derived from meta-analysis of data from both east Asian and European-ancestry populations. This study identified three new CRC susceptibility loci and provides additional insight into the genetics and biology of CRC.

Anthropometric and reproductive factors and the risk of pancreatic cancer : A case-control study in Shanghai, China

To examine the possible role of body size and reproductive factors in pancreatic cancer, data were analyzed from a population‐based case‐control study conducted in Shanghai, China. Cases (n = 451) were permanent residents of Shanghai, 30–74 years of age, newly diagnosed with pancreatic cancer between October 1, 1990, and June 30, 1993. Deceased cases (19%) were excluded from the study. Controls (n = 1,552) were randomly selected from permanent Shanghai residents and frequency‐matched to cases by gender and age. Information on body size and reproductive and other possible risk factors was collected through personal interviews. After adjustment for age, income, smoking and other confounders, a positive dose‐response relation between body mass index and risk of pancreatic cancer was observed in both sexes. Among women, the risk of pancreatic cancer was significantly associated with number of pregnancies and live births. Compared with 0–2 pregnancies or live births, the odds ratio (OR) for 8 or more pregnancies was 1.90, while that for 5 or more births was 1.88. A modest elevation in risk, independent of parity, was associated with early age at first birth. Risk increased over 40% among women with a first birth at or before age 19 years relative to those at age 26 years or older. Ever use of oral contraceptives was associated with excess risk, though based on small numbers of users. Our findings suggest that, in Shanghai, obesity, gravidity, parity and perhaps use of oral contraceptives are associated with moderate increases in risk of pancreatic cancer, indicating that hormonal determinants deserve further investigation.

A Common Deletion in the APOBEC3 Genes and Breast Cancer Risk

BACKGROUND Genome-wide association studies (GWASs) have identified multiple genetic susceptibility loci for breast cancer. However, these loci explain only a small fraction of the heritability. Very few studies have evaluated copy number variation (CNV), another important source of human genetic variation, in relation to breast cancer risk. METHODS We conducted a CNV GWAS in 2623 breast cancer patients and 1946 control subjects using data from Affymetrix SNP Array 6.0 (stage 1). We then replicated the most promising CNV using real-time quantitative polymerase chain reaction (qPCR) in an independent set of 4254 case patients and 4387 control subjects (stage 2). All subjects were recruited from population-based studies conducted among Chinese women in Shanghai. RESULTS Of the 268 common CNVs (minor allele frequency ≥ 5%) investigated in stage 1, the strongest association was found for a common deletion in the APOBEC3 genes (P = 1.1×10(-4)) and was replicated in stage 2 (odds ratio =1.35, 95% confidence interval [CI] = 1.27 to 1.44; P = 9.6×10(-22)). Analyses of all samples from both stages using qPCR data produced odds ratios of 1.31 (95% CI = 1.21 to 1.42) for a one-copy deletion and 1.76 (95% CI = 1.57 to 1.97) for a two-copy deletion (P = 2.0×10(-24)). CONCLUSIONS We provide convincing evidence for a novel breast cancer locus at the APOBEC3 genes. This CNV is one of the strongest common genetic risk variants identified so far for breast cancer.

Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1

In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P = 8.82 × 10−9), rs10474352 at 5q14.3 (near the ARRDC3 gene; P = 1.67 × 10−9) and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene; P = 4.25 × 10−8). We replicated these associations in 16,003 cases and 41,335 controls of European ancestry (P = 0.030, 0.004 and 0.010, respectively). Data from the ENCODE Project suggest that variants rs4951011 and rs10474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.

Combined impact of lifestyle-related factors on total and cause-specific mortality among chinese women: Prospective cohort study

Findings from the Shanghai Womens Health Study confirm those derived from other, principally Western, cohorts regarding the combined impact of lifestyle-related factors on mortality.

Glutathione S-transferase genotypes and stomach cancer in a population-based case-control study in Warsaw, Poland

Glutathione S-transferases are important in the detoxification of a wide range of human carcinogens. Previous studies have shown inconsistent associations between the GSTT1 and GSTM1 null genotypes and stomach cancer risk. We investigated the relationship between these and related genotypes and stomach cancer risk in a population-based case-control study in Warsaw, Poland, where stomach cancer incidence and mortality rates are among the highest in Europe. DNA from blood samples was available for 304 stomach cancer patients and 427 control subjects. We observed a 1.48-fold increased risk for stomach cancer (95% confidence interval 0.97-2.25) in patients with the GSTT1 null genotype but no evidence of increased risk associated with the GSTM1, GSTM3 or GSTP1 genotypes. Furthermore, the stomach cancer risk associated with the GSTT1 null genotype varied by age at diagnosis, with odds ratios of 3.85, 1.91, 1.78 and 0.59 for those diagnosed at ages less than 50, 50-59, 60-69 and 70 years or older, respectively (P trend = 0.01). This was due to a shift in the GSTT1 genotype distribution across age groups among stomach cancer patients only. These results suggest that the GSTT1 null genotype may be associated with increased risk of stomach cancer.

Dietary carbohydrates, fiber, and breast cancer risk in Chinese women

BACKGROUND Few studies have investigated the association of dietary carbohydrate and fiber intake with breast cancer risk in women in China, where carbohydrate intake is traditionally high. OBJECTIVE The objective was to prospectively evaluate the association of dietary carbohydrates, glycemic index, glycemic load, and dietary fiber with breast cancer risk and to determine whether the effect of these dietary intakes is modified by age and selected insulin- or estrogen-related risk factors. DESIGN A total of 74,942 women aged 40-70 y were recruited into the Shanghai Womens Health Study, a population-based cohort study. Dietary intake was assessed by in-person interviews. A Cox proportional hazards regression model was used to evaluate associations. RESULTS During an average of 7.35 y of follow-up, 616 incident breast cancer cases were documented. A higher carbohydrate intake was associated with a higher risk of premenopausal breast cancer (P for trend = 0.002). Compared with the lowest quintile, the hazard ratios (and 95% CIs) were 1.47 (1.00, 2.32) and 2.01 (1.26, 3.19) for the fourth and fifth quintiles, respectively. A similar pattern was found for glycemic load. The association between carbohydrate intake and breast cancer was significantly modified by age; the increased breast cancer risk associated with carbohydrate intake was restricted to women who were younger than 50 y. No significant association of breast cancer risk with glycemic index or dietary fiber intake was found. CONCLUSION Our data suggest that a high carbohydrate intake and a diet with a high glycemic load may be associated with breast cancer risk in premenopausal women or women <50 y.

Body fat distribution and risk of diabetes among Chinese women

OBJECTIVE: To assess the relationship between measures of central and overall obesity and risk of diabetes.DESIGN: Nested case–control study.SETTING: Shanghai, China.PARTICIPANTS: A total of 57 130 women were screened for diabetes at enrollment for the Shanghai Womens Health Study (SWHS), a population-based cohort study of Chinese women aged 40–70 y. In this study, 345 women diagnosed with diabetes and 2760 age-matched controls (eight controls per case), randomly selected from women who tested negative for urine glucose, were included.RESULTS: Risk of diabetes increased significantly with increasing levels of obesity, particularly with measures of central obesity. Compared to those in the lowest quartile, women in the highest quartile of body mass index (BMI) (≥26.57) and waist to hip ratio (WHR) (≥0.855) had a 2.57-fold (95% CI 1.75–3.77) and a 6.05-fold (95% CI 4.05–9.04) increased risk of diabetes, respectively. The risk of diabetes was elevated with increasing WHR at all levels of BMI, while the positive association between BMI and diabetes was observed primarily among women with a low WHR. However, test for multiplicative interaction was not statistically significant.CONCLUSIONS: Our data indicated that central obesity is a stronger risk factor for diabetes than overall obesity, suggesting that WHR may be a better indicator of risk of diabetes than BMI among Chinese women.