Prospective Cohort Study of Ginseng Consumption in Association with Cancer Risk: Shanghai Women's Health Study.

BACKGROUND: Ginseng has been commonly used in Asian countries to promote longevity and health for >2000 years. Recent in vitro and in vivo studies, coupled with limited epidemiologic studies, have suggested that regular ginseng consumption may be related to lower cancer risk. OBJECTIVES: We evaluated the association of ginseng consumption with risk of total and 15 site-specific cancers in a large cohort study conducted among Chinese women. Given the previous literature on ginseng consumption and cancer risk, we hypothesized that ginseng consumption might be associated with varying risks of cancer. METHODS: This study included 65,732 female participants (mean age: 52.2 years) of the Shanghai Women's Health Study, an ongoing prospective cohort study. Baseline enrollment occurred between 1997 and 2000, and follow-up concluded on 31 December 2016. Ginseng use and covariates were assessed via an in-person interview conducted at the baseline recruitment. The cohort was followed for cancer incidence. Cox proportional hazard models were used to estimate HRs and 95% CIs for ginseng-cancer associations after adjusting for confounders. RESULTS: During a mean 14.7 years of follow-up, 5067 incident cancer cases were identified. Overall, regular ginseng use was mostly not associated with risk of any site-specific cancer, or all cancers combined. Short-term (<3 years) ginseng use was found to be significantly associated with increased risk of liver cancer (HR = 1.71; 95% CI: 1.04, 2.79; P = 0.035), whereas long-term (≥3 years) ginseng use was found to be associated with increased risk of thyroid cancer (HR = 1.40; 95% CI: 1.02, 1.91; P = 0.036). Long-term ginseng use was found to be significantly associated with decreased risk of lymphatic and hematopoietic tissue malignancy (HR = 0.67; 95% CI: 0.46, 0.98; P = 0.039) and non-Hodgkin's lymphoma (HR = 0.57; 95% CI: 0.34, 0.97; P = 0.039). CONCLUSIONS: This study provides suggestive evidence that ginseng consumption may be associated with risk of certain cancers.

Association of Ginseng Consumption With All-cause and Cause-specific Mortality: Shanghai Women's Health Study.

BACKGROUND: Ginseng, an herbal remedy, has been commonly used in Asian countries to promote longevity and health for over 2,000 years. However, the association of ginseng consumption with all-cause and cause-specific mortality is still unclear. We analyzed the association of total and major cause-specific mortality (cardiovascular disease [CVD], cancer, and other death) with consumption of ginseng (primarily American and white ginseng). METHODS: This study included 56,183 female participants with an average follow-up of 14.7 years in the Shanghai Women's Health Study, an ongoing prospective cohort study. Data were assessed via an in-person interview conducted at baseline recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ginseng-mortality associations after adjusting for confounders. RESULTS: Compared with those who never used ginseng, regular ginseng use was associated with significantly reduced all-cause mortality (HR 0.92; 95% CI, 0.87-0.98). This inverse association was seen primarily among those who consumed ginseng for perceived general health benefit (HR 0.90; 95% CI, 0.85-0.96). A significant dose-response association was observed between duration of ginseng use and total mortality (HR 0.85, for using ≥6 years vs never use; P for trend <0.001), CVD mortality (HR 0.83; P for trend = 0.019), and other-cause mortality (HR 0.76; P for trend = 0.001). However, no dose-response association was observed between amount of ginseng consumption and mortality outcomes. CONCLUSION: Regular ginseng consumption, particularly over a long duration, was associated with decreased risk of all causes of death, death due to CVD, and death due to certain other diseases.

Phytoestrogens and lung cancer risk: a nested case-control study in never-smoking Chinese women.

BACKGROUND: Since several lines of evidence suggest that estrogens may be involved in lung carcinogenesis, it has been hypothesized that intake of phytoestrogens, similar in molecular structure to mammalian estrogens, may be associated with lung cancer development. OBJECTIVE: The aim was to prospectively evaluate the association between phytoestrogen exposure and lung cancer risk in never-smoking women. METHODS: We conducted a nested case-control study within a population-based prospective cohort study of women. A total of 478 incident lung cancer cases and their individually matched controls were identified among never-smoking women after a mean follow-up of 15.6 years. Habitual intake of and internal exposure to phytoestrogens were assessed by repeated dietary surveys and urinary biomarkers, respectively. ORs and 95% CIs for lung cancer were estimated in conditional logistic regression models. RESULTS: After adjustment for potential confounders, a moderate intake of dietary isoflavones was inversely associated with lung cancer risk in never-smoking women, with the OR for the second quartile vs. the lowest quartile of intake being 0.52 (95% CI: 0.35, 0.76). Further increasing intake did not convey additional benefits, with ORs (95% CI) for the third and fourth quartiles of 0.53 (0.36, 0.78) and 0.47 (0.31, 0.72), respectively (P-overall < 0.001 and P-nonlinearity = 0.006). A similar association was seen when exposure to isoflavones was assessed by urinary biomarkers. ORs (95% CI) for the second, third, and fourth quartiles compared with the lowest quartile of urinary isoflavone excretion were 0.57 (0.39, 0.83), 0.64 (0.44, 0.92), and 0.60 (0.41, 0.86), respectively. The inverse association reached a plateau beyond the second quartile, with P-overall = 0.04 and P-nonlinearity = 0.15. Urinary excretion of gut-microbiota-derived metabolites of lignans was not related to lung cancer risk. CONCLUSIONS: This study suggests that moderately increasing intake of isoflavone-rich foods is associated with lower risk of lung cancer in never-smoking women.

Food intake of folate, folic acid and other B vitamins with lung cancer risk in a low-income population in the Southeastern United States.

PURPOSE: We prospectively examined associations of lung cancer risk with food intake of B vitamins involved in one-carbon metabolism and the use of folic acid-containing supplements among a low-income population of black and white adults in the Southeastern US. METHODS: Within the Southern Community Cohort Study, we included 1064 incident lung cancer cases among 68,236 participants aged 40-79 years at study enrollment. Food intake and the use of folic acid-containing supplements were assessed using a validated food frequency questionnaire at study enrollment. Multivariate Cox regression was used to estimate hazards ratios (HRs) and the 95% confidence intervals (CIs). RESULTS: Folate and/or folic acid intake from food were not associated with lung cancer risk; HRs (95% CI) for highest compared with lowest quartile were 1.08 (0.91-1.29) for total dietary folate, 1.00 (0.84-1.19) for food folate, and 1.09 (0.91-1.30) for food folic acid, respectively. Similarly, no associations were observed after stratifying by sex, race and smoking status, except for a positive association with total dietary folate intake among black women (HR 1.46, 95% CI 1.04-2.05 for the highest quartile compared with the lowest quartile, P trend = 0.02). Neither the use of folic acid-containing supplements nor food intake of vitamin B6, vitamin B12 and riboflavin were associated with lung cancer risk. CONCLUSIONS: Our findings do not support a protective effect of folate or folic acid for lung cancer prevention in a low-income population of black and white adults in the Southeastern US. Our finding of a positive association with total dietary folate intake among black women needs to be interpreted with caution and replicated in other studies.

Transcriptome-Wide Association Study Identifies Susceptibility Loci and Genes for Age at Natural Menopause.

OBJECTIVE: To identify novel susceptibility genes for age at natural menopause (ANM). METHODS: Using transcription data generated in tissues from normal hypothalami (n = 73) and ovaries (n = 68) and high-density genotyping data provided by the Genotype-Tissue Expression (GTEx) database, we built 16 164 genetic models to predict gene expression across the transcriptome in these tissues. We used these models and summary statistics data from genome-wide association studies (GWAS) of ANM generated in 69 360 women of European ancestry to identify genes with their predicted expression related to ANM. RESULTS: We found the predicted expression of 34 genes to be significantly associated with ANM at a Bonferroni-corrected threshold of P < 3.09 ×10-6. These include 4 genes located more than 1 Mb away from any previously GWAS-identified ANM-associated variants, 24 genes that reside in known GWAS-identified loci but have not been previously implicated, and 6 genes previously implicated as ANM-associated genes. CONCLUSION: Results from this transcriptome-wide association study, which integrated Expression quantitative trait loci (eQTL) data with summary statistics of GWAS of ANM, improves our understanding of the genetics and biology of female reproductive aging.

Are dietary antioxidant intake indices correlated to oxidative stress and inflammatory marker levels?

Epidemiologic and experimental studies have shown that a high intake of individual dietary antioxidants is associated with a reduced risk of cancers. Few studies, however, have investigated the influences of a combination of dietary antioxidants. We evaluated the association of two dietary antioxidant indices, the Dietary Antioxidant Quality Score (DAQS) and the Composite Dietary Antioxidant Index (CDAI), with 10 oxidative stress or inflammation biomarkers (urinary F2-isoprostanes [15-F2t-IsoP]; urinary F2-isoprostane metabolites [15-F2t-IsoPM]; urinary prostaglandin E2 metabolite [PGEM]; C-reactive protein [CRP]; interleukin-1beta [IL-1ß]; interleukin-6 [IL-6]; tumor necrosis factor-alpha [TNF-α]; soluble TNF-receptor 1 [sTNF-R1]; soluble TNF-receptor 2 [sTNF-R2]; and soluble GP130 [sGP130]) in 3853 participants of the Shanghai Women's Health Study (SWHS). We found the DAQS and CDAI to be highly correlated (r=0.72), and both were inversely associated with levels of IL-1ß (ptrend=0.02 and 0.03, respectively) and TNF-α (ptrend=0.005 and 0.003, respectively). In addition, IL-6 and sTNF-R2 levels were inversely associated with the DAQS score; ß-coefficient(±SE) for average-quality and high-quality group versus low-quality group were -0.22(±0.13) and -0.30(±0.13) (ptrend=0.06) for IL-6; -0.06(±0.04) and -0.10(±0.04) (ptrend=0.01) for sTNF-R2. Neither the DAQS nor CDAI score was significantly associated with oxidative stress or other inflammatory biomarkers. Our observations lead us to hypothesize that these two indices offer a potential aggregate method of measuring dietary anti-inflammation, but not anti-oxidation properties.

Dietary polyunsaturated fatty acids and breast cancer risk in Chinese women: a prospective cohort study.

Breast cancer is the most common cancer in women. Controversy exists regarding the role of dietary fat in breast cancer etiology. We investigated the association of dietary polyunsaturated fatty acids (PUFAs) and the ratio of n-6 PUFAs to marine-derived n-3 PUFAs with breast cancer risk in the Shanghai Women's Health Study, a prospective cohort study including 72,571 cancer-free participants at baseline. Dietary fatty acid intake was determined using food frequency questionnaires. We used Cox proportional hazards analysis to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for the association of breast cancer risk with dietary fatty acids consumption. In 583,998 person-years of follow-up, we identified 712 breast cancer cases. We found no association of breast cancer risk to dietary intake of linoleic acid, arachidonic acid, α-linolenic acid or marine-derived n-3 PUFA. We found a statistically significant interaction between n-6 PUFA intake, marine-derived n-3 PUFA intake and breast cancer risk (p = 0.008). Women with lower intake (the lowest tertile) of marine-derived n-3 PUFA and higher intake (the highest tertile) of n-6 PUFA had an increase risk for breast cancer (RR = 2.06; 95% CI = 1.27-3.34) compared to women with higher intake (the highest tertile) of marine-derived n-3 PUFAs and lower intake (the lowest tertile) of n-6 PUFAs after adjusting for potential confounders. The relative amounts of n-6 PUFA to marine-derived n-3 PUFAs may be more important for breast cancer risk than individual dietary amounts of these fatty acids.

Is green tea drinking associated with a later onset of breast cancer?

BACKGROUND: Studies have found that tea polyphenols inhibit aromatase. Because of the substantial difference in levels of estrogens between premenopausal and postmenopausal women, the relationship between tea consumption and breast cancer risk may depend on menopausal status. METHODS: We examined this hypothesis in the Shanghai Women's Health Study, a population-based cohort study of 74,942 Chinese women. RESULTS: We found a time-dependent interaction between green tea consumption and age of breast cancer onset (p for interaction, 0.03). In comparison with non-tea drinkers, women who started tea-drinking at 25 years of age or younger had a hazard ratio (HR) of 0.69 (95% confidence interval [CI]: 0.41-1.17) to develop premenopausal breast cancer. On the other hand, compared with non-tea drinkers, women who started tea drinking at 25 years of age or younger had an increased risk of postmenopausal breast cancer with an HR of 1.61 (95% CI: 1.18-2.20). Additional analyses suggest regularly drinking green tea may delay the onset of breast cancer. CONCLUSIONS: Further studies are needed to confirm our findings.

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 Women's 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.

Spousal correlations for lifestyle factors and selected diseases in Chinese couples.

PURPOSE: Spouses usually are genetically unrelated and share a common living environment. Thus, concordance of diseases in spouses reflects mainly environmental etiologic contributors. The purpose of this study is to investigate spousal associations for selected lifestyle characteristics and common medical conditions. METHODS: Baseline information from 66,130 married couples participating in the Shanghai Women's Health Study was used in this analysis. Husband-wife associations were evaluated by means of logistic regression, using women's lifestyle and medical conditions as dependent variables. Adjustments were made for women's age, education, occupation, and family income in all models. RESULTS: Women were more than twice as likely to be current or former smokers; be regular consumers of alcohol, tea, and ginseng; and exercise regularly if their husbands had the same habit. A statistically significant husband-wife disease association was found for tuberculosis, chronic bronchitis, asthma, chronic gastritis, chronic hepatitis, ulcerative colitis, cholelithiasis, high blood pressure, coronary heart disease, and stroke. CONCLUSIONS: Spouses share common lifestyle habits and health risks. This study supports the hypothesis that the shared marital environment may contribute to similarities in lifestyle and morbidity in spouses and provides a basis for health promotion and prevention strategies that target the spouses of patients.

Genetic polymorphism in the manganese superoxide dismutase gene, antioxidant intake, and breast cancer risk: results from the Shanghai Breast Cancer Study.

INTRODUCTION: It has been suggested that oxidative stress and mitochondrial DNA damage play important roles in breast cancer carcinogenesis. Manganese superoxide dismutase (MnSOD) is a major enzyme that is responsible for the detoxification of reactive oxygen species in the mitochondria. A T --> C substitution in the MnSOD gene results in a Val --> Ala change at the -9 position of the mitochondrial targeting sequence (Val-9Ala), which alters the protein secondary structure and thus affects transport of MnSOD into the mitochondria. METHODS: We evaluated this genetic polymorphism in association with breast cancer risk using data from the Shanghai Breast Cancer Study, a population-based case-control study conducted in urban Shanghai from 1996 to 1998. The MnSOD Val-9Ala polymorphism was examined in 1125 breast cancer cases and 1197 age-frequency-matched control individual. RESULTS: Breast cancer risk was slightly elevated in women with Ala/Ala genotype (odds ratio [OR] 1.3, 95% confidence interval [CI] 0.7-2.3), particularly among premenopausal women (OR 1.8, 95% CI 0.9-3.7), as compared with those with Val/Val genotype. The increased risk with the Ala/Ala genotype was stronger among premenopausal women with a higher body mass index (OR 2.5, 95% CI 0.9-7.0) and more years of menstruation (OR 2.6, 95% CI 0.8-8.0). The risk among premenopausal women was further increased twofold to threefold among those with a low intake of fruits, vegetables, vitamin supplements, selenium, or antioxidant vitamins, including carotenes and vitamins A, C, and E. However, the frequency of the Ala allele was low (14%) in the study population, and most of the ORs provided above were not statistically significant. CONCLUSION: The present study provides some evidence that genetic polymorphism in the MnSOD gene may be associated with increased risk of breast cancer among Chinese women with high levels of oxidative stress or low intake of antioxidants. Studies with a larger sample size are needed to confirm the findings.

Use of complementary and alternative medicine by chinese women with breast cancer.

The use of complementary and alternative medicine (CAM) has been rapidly increasing among cancer patients. The aim of this study is to evaluate the prevalence and patterns of CAM use, particularly patients' intentions and their perceived effectiveness of using Chinese herbal medicine (CHM), as well as the relations between the herbal medicine use and demographic and clinical factors among Chinese women with breast cancer. We analyzed the data from a population-based sample of 1065 breast cancer women in urban Shanghai. Patients' average age at diagnosis was 48.1 years and the median time from the initial diagnosis to the follow-up survey was 4.3 years. Overall, 98% of patients had used at least one form of CAM therapy after diagnosis of breast cancer. The most popular CAM modality was traditional Chinese medicine (86.7%), followed by the use of supplements (84.8%), physical exercises (65.5%), and support group attendance (16.6%). CHM was used by 86.4% of patients, while acupuncture was used only by 4.9% of patients. Treating cancer (81.5%) was the most common intentions of using CHM. Other cited intentions included enhancing the immune system (12%), preventing metastasis of cancer or managing other discomforts (7.9%), and lessening menopausal symptoms (4.7%). The majority of patients reported that they had benefited from the use of CHM. Patients who were younger, married, had higher education or income, received chemotherapy or radiotherapy, or had recurrence/metastasis of cancer tended to use CHM more frequently than other patients. The relations between patient characteristics and use of CHMs varied with users' intentions. Given the high prevalence of CAM use among breast cancer patients, research is urgently needed to systematically evaluate the efficacy and safety of CAM use, particularly use of herbal medicines.

Parental medication use and risk of childhood acute lymphoblastic leukemia.

BACKGROUND: Few studies have examined the risk of childhood acute lymphoblastic leukemia (ALL) associated with parental medication use. As part of a large case-control study conducted by the Children's Cancer Group, we evaluated the association between maternal and paternal medication use and the risk of ALL in offspring. METHODS: Information on selected medication use in the year before and during the index pregnancy was obtained by telephone interview. Participants included 1842 children of 14 years or younger with newly diagnosed and immunophenotypically defined ALL and 1986 individually matched controls. Data were analyzed using logistic regression models and stratified by immunophenotypes of ALL and age at diagnosis of cases. RESULTS: After adjusting for potential confounders and other medication use, we found that maternal use of vitamins (odds ratio [OR] = 0.7, 99% confidence interval [CI]: 0.5-1.0) and iron supplements (OR = 0.8, 99% CI: 0.7-1.0) only during the index pregnancy was associated with a decreased risk of ALL. Parental use of amphetamines or diet pills and mind-altering drugs before and during the index pregnancy was related to an increased risk of childhood ALL, particularly among children where both parents reported using these drugs (OR = 2.8, 99% CI: 0.5-15.6 for amphetamines or diet pills, OR = 1.8, 99% CI: 1.1-3.0 for mind-altering drugs). Stratified analyses showed that maternal use of antihistamines or allergic remedies and parental use of mind-altering drugs were strongly associated with infant ALL, whereas patterns of association between childhood ALL and parental medication use did not influence markedly the immunophenotypic subgroup of ALL. CONCLUSIONS: The findings of this study suggest that certain parental medication use immediately before and during the index pregnancy may influence risk of ALL in offspring.