Xuejuan Jiang

Lipid peroxidation, oxidative stress genes and dietary factors in breast cancer protection: a hypothesis

We have recently proposed that lipid peroxidation may be a common mechanistic pathway by which obesity and hypertension lead to increased renal cell cancer risk. During this exercise, we noted a risk factor swap between breast and kidney cancer (oophorectomy and increased parity, detrimental for kidney, beneficial for breast; high blood pressure, detrimental for kidney, beneficial for breast when it occurs during pregnancy; alcohol, beneficial for kidney, detrimental for breast, and so on). We have subsequently proposed the hypothesis that lipid peroxidation represents a protective mechanism in breast cancer, and reviewed the evidence of the role of lipid peroxidation on established hormonal and non-hormonal factors for breast cancer. Here, we review the evidence in support of lipid peroxidation playing a role in the relationships between dietary factors and breast cancer. Available evidence implicates increased lipid peroxidation products in the anti-carcinogenic effect of suspected protective factors for breast cancer, including soy, marine n-3 fatty acids, green tea, isothiocyanates, and vitamin D and calcium. We also review the epidemiological evidence supporting a modifying effect of oxidative stress genes in dietary factor-breast cancer relationships.

Baseline Risk Factors that Predict the Development of Open-Angle Glaucoma in a Population: The Los Angeles Latino Eye Study

OBJECTIVE To determine which baseline sociodemographic, lifestyle, anthropometric, clinical, and ocular risk factors predict the development of open-angle glaucoma (OAG) in an adult population. DESIGN A population-based, prospective cohort study. PARTICIPANTS A total of 3772 self-identified Latinos aged ≥40 years from Los Angeles, California, who were free of OAG at baseline. METHODS Participants from the Los Angeles Latino Eye Study had standardized study visits at baseline and 4-year follow-up with structured interviews and a comprehensive ophthalmologic examination. We defined OAG as the presence of an open angle and a glaucomatous visual field abnormality and/or evidence of glaucomatous optic nerve damage in ≥1 eye. Multivariate logistic regression with stepwise selection was performed to determine which potential baseline risk factors independently predict the development of OAG. MAIN OUTCOME MEASURES Odds ratios for various risk factors. RESULTS Over the 4-year follow-up, 87 participants developed OAG. The baseline risk factors that predict the development of OAG include older age (odds ratio [OR] per decade, 2.19; 95% confidence interval [CI], 1.74-2.75; P<0.001), higher intraocular pressure (IOP; OR per mmHg, 1.18; 95% CI, 1.10-1.26; P<0.001), longer axial length (OR per mm, 1.48; 95% CI, 1.22-1.80; P<0.001), thinner central cornea (OR per 40 μm thinner, 1.30; 95% CI, 1.00-1.70; P = 0.050), higher waist-to-hip ratio (OR per 0.05 higher, 1.21; 95% CI, 1.05-1.39; P = 0.007) and lack of vision insurance (OR, 2.08; 95% CI, 1.26-3.41; P = 0.004). CONCLUSIONS Despite a mean baseline IOP of 14 mmHg in Latinos, higher IOP is an important risk factor for developing OAG. Biometric measures suggestive of less structural support such as longer axial length and thin central corneal thickness were identified as important risk factors. Lack of health insurance reduces access to eye care and increases the burden of OAG by reducing the likelihood of early detection and treatment of OAG. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Environmental Tobacco Smoke and Bladder Cancer Risk in Never Smokers of Los Angeles County

Cigarette smoking is a major risk factor for bladder cancer and a prominent point source of 4-aminobiphenyl (4-ABP), a recognized human bladder carcinogen. 4-ABP-hemoglobin (Hb) adducts are established biomarkers of 4-ABP exposure in humans. The role of environmental tobacco smoke (ETS) in the etiology of bladder cancer is largely unknown. As part of a large population-based bladder cancer study in Los Angeles County, California, lifetime exposure to ETS was ascertained for 148 cases and 292 control subjects who had never used any tobacco products over their lifetime. 4-ABP-Hb adducts were quantitatively measured on 230 control subjects. Female lifelong nonsmokers living with two or more smokers during childhood were significantly related to risk of bladder cancer [odds ratio (OR), 3.08; 95% confidence interval (95% CI), 1.16-8.22]. During adulthood, approximately 2-fold risks were seen among women living with a spouse/domestic partner who smoked for > or =10 years or having a coworker who smoked in an indoor environment for > or =10 years. When all sources of ETS exposure were combined, a statistically significant, dose-dependent association (P for trend = 0.03) was noted in women, with the OR for the highest category of ETS exposure being 5.48 (95% CI, 1.06-28.36). Levels of 4-ABP-Hb adducts varied by ETS exposure status among female control subjects. Mean level was lowest in women never exposed to ETS (16.4 pg/g Hb) and highest in those with current ETS exposure (23.6 pg/g Hb). ETS exposure was associated with neither bladder cancer risk nor 4-ABP-Hb adduct levels in male lifelong nonsmokers. In conclusion, ETS is a risk factor for bladder cancer in women who were lifelong nonusers of any tobacco products.

Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study.

Genome-wide association studies have associated common variations at chromosomes 5p15 and 15q25 with lung cancer risk. The 5p15 locus has also been associated with increased bladder cancer risk in a recent report. The 15q25 locus has been associated with nicotine dependence and self-reported number of cigarettes smoked per day in some studies and it was proposed that its association with lung cancer may be mediated through differences in smoking behavior. Here, we investigated the roles of variations at 5p15 (rs401681, rs402710, rs2736098 and rs2736100) and 15q25 (rs1051730 and rs8034191) in bladder cancer etiology in two case-control studies conducted separately in Los Angeles County, CA, USA (498 cases and 588 controls) and in Shanghai, China (506 cases and 530 controls). We replicated the association between the 5p15 locus and bladder cancer among non-Hispanic whites (NHW) in Los Angeles [for rs2736100, per C allele odds ratio (OR) = 1.23; 95% confidence interval (CI), 1.02-1.48; P = 0.029] and among Chinese in Shanghai (OR = 1.22; 95% CI, 1.02-1.47; P = 0.033). Both rs1051730 and rs8034191 at 15q25 were rare among Chinese. Among NHW, a significant association was found between rs8034191 and bladder cancer which persisted after adjustment for cigarette smoking status, number of cigarettes smoked per day and number of years of smoking (per C allele OR = 1.26; 95% CI, 1.04-1.54; P = 0.017). Our results support 5p15 and 15q25 as susceptibility regions for bladder cancer risk.

Cigarette smoking and subtypes of bladder cancer

There is little information regarding associations between suspected bladder cancer risk factors and tumor subtypes at diagnosis. Some, but not all, studies have found that bladder cancer among smokers is often more invasive than it is among nonsmokers. This population‐based case‐control study was conducted in Los Angeles, California, involving 1,586 bladder cancer patients and their individually matched controls. Logistic regression was used to conduct separate analyses according to tumor subtypes defined by stage and grade. Cigarette smoking increased risk of both superficial and invasive bladder cancer, but the more advanced the stage, the stronger the effect. The odds ratios associated with regular smokers were 2.2 (95% confidence intervals, 1.8–2.8), 2.7 (2.1–3.6) and 3.7 (2.5–5.5) for low‐grade superficial, high‐grade superficial and invasive tumors respectively. This pattern was consistently observed regardless of the smoking exposure index under examination. Women had higher risk of invasive bladder cancer than men even they smoked comparable amount of cigarettes as men. There was no gender difference in the association between smoking and risk of low‐grade superficial bladder cancer. The heterogeneous effect of cigarette smoking was attenuated among heavy users of NSAIDs. Our results indicate that cigarette smoking was more strongly associated with increased risk of invasive bladder cancer than with low‐grade superficial bladder cancer.

Water intake and bladder cancer risk in Los Angeles County

The overall evidence of an association between fluid intake and bladder cancer is not entirely consistent. We examined the fluid intake‐bladder cancer relationship in the Los Angeles bladder cancer case‐control study. A total of 1,586 cases and their age‐, sex‐, and race‐matched neighborhood controls were interviewed in‐person from 1987 to 1999. Information on total fluid intake was derived from the consumption of specific fluids including water, coffee, tea, alcohol, milk, juice, hot chocolate and soda. Total fluid intake was not associated with bladder cancer. Daily water intake was associated with a slight decrease in bladder cancer risk, with the protection more pronounced among women (p for trend = 0.039) than among men (p for trend = 0.62). Compared to drinking <1 glass of water per day, drinking ≥6 glasses/day was associated with 0.91 (95% confidence interval, 0.67–1.22) times the risk of bladder cancer among all subjects, 0.94 (0.67–1.32) times the risk among men, and 0.69 (0.36–1.33) times the risk among women. The water intake‐bladder cancer association also seemed to be modified by daytime urination frequency with significant inverse association among subjects who urinated ≥6 times/day (p for trend = 0.015), but not among those who urinated less frequently. Similarly, the protection from water intake was confined to women who did not experience nocturia and to men who did. Results from our study suggest that water intake may be associated with a slight reduction in bladder cancer risk.

Urinary tract infections and reduced risk of bladder cancer in Los Angeles

We investigated the association between urinary tract infections (UTIs) and transitional cell carcinoma of the bladder in a population-based case–control study in Los Angeles covering 1586 cases and age-, gender-, and race-matched neighbourhood controls. A history of bladder infection was associated with a reduced risk of bladder cancer among women (odds ratio (OR), 0.66; 95% confidence interval (CI), 0.46–0.96). No effect was found in men, perhaps due to power limitations. A greater reduction in bladder cancer risk was observed among women with multiple infections (OR, 0.37; 95% CI, 0.18–0.78). Exclusion of subjects with a history of diabetes, kidney or bladder stones did not change the inverse association. A history of kidney infections was not associated with bladder cancer risk, but there was a weak association between a history of other UTIs and slightly increased risk among men. Our results suggest that a history of bladder infection is associated with a reduced risk of bladder cancer among women. Cytotoxicity from antibiotics commonly used to treat bladder infections is proposed as one possible explanation.

Combination of Molecular Alterations and Smoking Intensity Predicts Bladder Cancer Outcome: A Report from the Los Angeles Cancer Surveillance Program

Traditional single‐marker and multimarker molecular profiling approaches in bladder cancer do not account for major risk factors and their influence on clinical outcome. This study examined the prognostic value of molecular alterations across all disease stages after accounting for clinicopathological factors and smoking, the most common risk factor for bladder cancer in the developed world, in a population‐based cohort.

Alcohol consumption and risk of bladder cancer in Los Angeles County

The role of alcoholic beverages in bladder carcinogenesis is still unclear, with conflicting evidence from different studies. We investigated the relationship between alcohol consumption and bladder cancer, and the potential interaction between alcohol consumption and other exposures. In a population‐based case–control study conducted in Los Angeles County, 1,586 pairs of cases and their matched neighborhood controls were interviewed. Data were analyzed to determine whether bladder cancer risk differs by alcohol consumption, and whether different alcoholic beverages have different effects. The risk of bladder cancer decreased with increasing frequency (p for trend = 0.003) and duration of alcohol consumption (p for trend = 0.017). Subjects who drank more than 4 drinks per day had a 32% lower (odds ratio, 0.68; 95% confidence interval, 0.52–0.90) risk of bladder cancer than those who never drank any alcoholic beverage. Beer (p for trend = 0.002) and wine (p for trend = 0.054) consumption were associated with reduced risk of bladder cancer, while hard liquor was not. The reduction in risk was mostly seen among shorter‐term smokers who urinated frequently. Alcohol consumption was strongly associated with a reduced risk of bladder cancer. The effect was modified by the type of alcoholic beverage, cigarette smoking and frequency of urination.

Breast Feeding, Parity and Breast Cancer Subtypes in a Spanish Cohort

Background Differences in the incidence and outcome of breast cancer among Hispanic women compared with white women are well documented and are likely explained by ethnic differences in genetic composition, lifestyle, or environmental exposures. Methodolgy/Principal Findings A population-based study was conducted in Galicia, Spain. A total of 510 women diagnosed with operable invasive breast cancer between 1997 and 2010 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics were collected. The different breast cancer tumor subtypes were compared on their clinico-pathological characteristics and risk factor profiles, particularly reproductive variables and breastfeeding. Among the 501 breast cancer patients (with known ER and PR receptors), 85% were ER+/PR+ and 15% were ER-&PR-. Among the 405 breast cancer with known ER, PR and HER2 status, 71% were ER+/PR+/HER2- (luminal A), 14% were ER+/PR+/HER2+ (luminal B), 10% were ER−/PR−/HER2- (triple negative breast cancer, TNBC), and 5% were ER−/PR−/HER2+ (non-luminal). A lifetime breastfeeding period equal to or longer than 7 months was less frequent in case patients with TNBC (OR = 0.25, 95% CI = 0.08–0.68) compared to luminal A breast cancers. Both a low (2 or fewer pregnancies) and a high (3–4 pregnancies) number of pregnancies combined with a long breastfeeding period were associated with reduced odds of TNBC compared with luminal A breast cancer, although the association seemed to be slightly more pronounced among women with a low number of pregnancies (OR = 0.09, 95% CI = 0.005–0.54). Conclusions/Significance In case-case analyses with the luminal A cases as the reference group, we observed a lower proportion of TNBC among women who breastfed 7 or more months. The combination of longer breastfeeding duration and lower parity seemed to further reduce the odds of having a TNBC compared to a luminal A breast cancer.