Combination of molecular alterations and smoking intensity predicts bladder cancer outcome: a report from the Los Angeles Cancer Surveillance Program.

BACKGROUND: 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. METHODS: Primary bladder tumors from 212 cancer registry patients (median follow-up, 13.2 years) were immunohistochemically profiled for Bax, caspase-3, apoptotic protease-activating factor 1 (Apaf-1), Bcl-2, p53, p21, cyclooxygenase-2, vascular endothelial growth factor, and E-cadherin alterations. "Smoking intensity" quantified the impact of duration and daily frequency of smoking. RESULTS: Age, pathological stage, surgical modality, and adjuvant therapy administration were significantly associated with survival. Increasing smoking intensity was independently associated with worse outcome (P < .001). Apaf-1, E-cadherin, and p53 were prognostic for outcome (P = .005, .014, and .032, respectively); E-cadherin remained prognostic following multivariable analysis (P = .040). Combined alterations in all 9 biomarkers were prognostic by univariable (P < .001) and multivariable (P = .006) analysis. A multivariable model that included all 9 biomarkers and smoking intensity had greater accuracy in predicting prognosis than models composed of standard clinicopathological covariates without or with smoking intensity (P < .001 and P = .018, respectively). CONCLUSIONS: Apaf-1, E-cadherin, and p53 alterations individually predicted survival in bladder cancer patients. Increasing number of biomarker alterations was significantly associated with worsening survival, although markers comprising the panel were not necessarily prognostic individually. Predictive value of the 9-biomarker panel with smoking intensity was significantly higher than that of routine clinicopathological parameters alone.

No association between the SRD5A2 gene A49T missense variant and prostate cancer risk: lessons learned.

The steroid 5-alpha reductase type II gene (SRD5A2) encodes the enzyme which converts testosterone (T) to the more active androgen dihydrotestosterone. A non-synonymous single-nucleotide polymorphism, A49T (rs9282858), in SRD5A2 has been implicated in prostate cancer risk; however, results have been inconsistent. In 1999, we reported a strong association between the A49T variant and prostate cancer risk among African-Americans and Latinos in the Hawaii-Los Angeles Multiethnic Cohort (MEC). We report here an updated analysis of MEC data including the five major ethnic groups of the MEC, an increased sample size, improved genotyping technology and a comprehensive meta-analysis of the published literature. We found a non-statistically significant positive association between prostate cancer risk and carrying either the AT or TT genotype [odds ratio (OR) = 1.16, 95% confidence interval (CI) 0.79-1.69] in the MEC. This finding is in contrast to our previous results of ORs of 3.28 and 2.50 for the association between prostate cancer risk and the variant in African-American and Latino men, respectively; this can be accounted for by genotyping error in our earlier study. Meta-analysis of the published literature, including the current MEC data, shows a summary OR of 1.13 (95% CI 0.95-1.34) for the A49T variant with prostate cancer risk among sporadic, unselected cases. After evaluating more than 6000 cases and 6000 controls, there is little evidence of a role for the SRD5A2 A49T variant in prostate cancer risk. Overall, this report highlights the importance of rigorous genotyping quality control measures and replication efforts in genetic association studies.

Adenomyosis and endometriosis in the California Teachers Study.

OBJECTIVE: To evaluate the reproductive and lifestyle correlates of a surgically confirmed diagnosis of endometriosis or adenomyosis in a large prospective cohort. DESIGN: Collection of surgical diagnoses of endometriosis and adenomyosis during follow-up of women with no prior history of endometriosis and no prior surgery for adenomyosis. SETTING: The California Teachers Study (CTS), an ongoing prospective study of female teachers and school administrators established from the rolls of the California State Teachers Retirement System. PATIENT(S): Women with surgical diagnoses of endometriosis and adenomyosis were identified from California statewide hospital patient discharge records for CTS cohort members with an intact uterus and no prior history of endometriosis. Women with an incident surgical diagnosis of endometriosis (n = 229) or adenomyosis (n = 961) were compared with disease-free women in the same age range (for endometriosis, n = 43,493; for adenomyosis, n = 79,495). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Multivariable logistic regression methods were used to calculate prevalence odds ratios and associated 95% confidence intervals for the associations between self-reported menstrual and reproductive characteristics and either endometriosis or adenomyosis. RESULT(S): Women surgically diagnosed with endometriosis were younger than those surgically diagnosed with adenomyosis. Factors statistically significantly associated with endometriosis were having a mother or sister with endometriosis and nulligravidity. Factors statistically significantly associated with adenomyosis were increasing parity, early menarche (

Beta-cryptoxanthin and lung cancer in Shanghai, China--an examination of potential confounding with cigarette smoking using urinary cotinine as a biomarker for true tobacco exposure.

Diet may be a modifier of smoking-related cancer risk, with protective effects of intake of fruits and vegetables and associated antioxidants found in many observational studies. We previously reported serum beta-cryptoxanthin levels being inversely associated with smoking-related lung cancer incidence in a cohort of Chinese men. We noted, however, that serum beta-cryptoxanthin is negatively correlated with smoking. Since self-reports of smoking intensity undoubtedly contain errors, this negative correlation indicates a potential bias in assessing the effects of beta-cryptoxanthin, due to confounding with the unmeasured (residual) portion of cigarette exposure. We evaluated cotinine levels in pre-diagnostic spot urine samples to attempt to improve smoking assessment. We noted that urinary cotinine levels correlated significantly with cigarette consumption overall and that cotinine was strongly predictive of lung cancer risk. Urinary cotinine, however, was not as strong a predictor of lung cancer risk in current smokers as were self-reports of cigarette consumption and cotinine remained only a marginally significant predictor of lung cancer risk after adjustment for self-reports. An apparent benefit of beta-cryptoxanthin remained evident when including both urinary cotinine and self-reported cigarette consumption and cotinine in the statistical model. However, we conclude that cotinine measured from a single spot urine seems to have only limited value in augmenting self-reports of cigarette consumption so that, at present, the apparent protective effects of beta-cryptoxanthin, as seen in our own study, should continue to be regarded as unproven. We believe that future epidemiological evaluation of the association between beta-cryptoxanthin (and other antioxidants) and reduced lung cancer risk must utilize improved biomarkers to augment smokers' own self-reports of smoking amount.

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.

Physical activity and colon cancer risk among women in the California Teachers Study.

BACKGROUND: Existing data suggest that physical activity reduces colon cancer risk, but the association is not consistently observed in women. One potential explanation for this inconsistency is that hormone therapy, which is associated with lower colon cancer risk, acts as a modifier of the physical activity/colon cancer relationship. METHODS: Participants in the California Teachers Study (N = 120,147), a prospective cohort of female teachers and administrators residing in California, ages 22 to 84 years at baseline and with no prior history of colon cancer were eligible for study. Between 1996 and 2002, 395 patients were diagnosed with invasive colon cancer. The relative risks (RR) associated with lifetime (high school through age 54 years or current age) and recent (past 3 years) strenuous and moderate recreational physical activity were estimated using Cox proportional hazards regression models. RESULTS: Combined lifetime moderate and strenuous recreational physical activity was only modestly associated with colon cancer risk in the cohort [>or=4 versus or=4 versus

Long-term recreational physical activity and risk of invasive and in situ breast cancer: the California teachers study.

BACKGROUND: Long-term physical activity may affect breast cancer risk. Few prospective studies have evaluated in situ or invasive breast cancer risk, or breast cancer receptor subtypes, in relation to long-term activity. METHODS: We examined the association between recreational physical activity and risk of invasive and in situ breast cancer in the California Teachers Study, a cohort of women established in 1995-1996. Of 110 599 women aged 20 to 79 years with no history of breast cancer followed up through December 31, 2002, 2649 were diagnosed as having incident invasive breast cancer and 593 were diagnosed as having in situ breast cancer. Information was collected at cohort entry on participation in strenuous and moderate recreational activities during successive periods from high school through the current age or age 54 years (if older at enrollment) and in the past 3 years. A summary measure of long-term activity up to the current age, or age 54 years if older, was constructed for each woman. RESULTS: Invasive breast cancer risk was inversely associated with long-term strenuous activity (>5 vs 5 vs

Diet and risk of ovarian cancer in the California Teachers Study cohort.

Dietary phytochemical compounds, including isoflavones and isothiocyanates, may inhibit cancer development but have not yet been examined in prospective epidemiologic studies of ovarian cancer. The authors have investigated the association between consumption of these and other nutrients and ovarian cancer risk in a prospective cohort study. Among 97,275 eligible women in the California Teachers Study cohort who completed the baseline dietary assessment in 1995-1996, 280 women developed invasive or borderline ovarian cancer by December 31, 2003. Multivariable Cox proportional hazards regression, with age as the timescale, was used to estimate relative risks and 95% confidence intervals; all statistical tests were two sided. Intake of isoflavones was associated with lower risk of ovarian cancer. Compared with the risk for women who consumed less than 1 mg of total isoflavones per day, the relative risk of ovarian cancer associated with consumption of more than 3 mg/day was 0.56 (95% confidence interval: 0.33, 0.96). Intake of isothiocyanates or foods high in isothiocyanates was not associated with ovarian cancer risk, nor was intake of macronutrients, antioxidant vitamins, or other micronutrients. Although dietary consumption of isoflavones may be associated with decreased ovarian cancer risk, most dietary factors are unlikely to play a major role in ovarian cancer development.

Wine and other alcohol consumption and risk of ovarian cancer in the California Teachers Study cohort.

OBJECTIVE: Whether alcohol consumption influences ovarian cancer risk is unclear. Therefore, we investigated the association between alcohol intake at various ages and risk of ovarian cancer. METHODS: Among 90,371 eligible members of the California Teachers Study cohort who completed a baseline alcohol assessment in 1995-1996, 253 women were diagnosed with epithelial ovarian cancer by the end of 2003. Multivariate Cox proportional hazards regression analysis was performed to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Consumption of total alcohol, beer, or liquor in the year prior to baseline, at ages 30-35 years, or at ages 18-22 years was not associated with risk of ovarian cancer. Consumption of at least one glass per day of wine, compared to no wine, in the year before baseline was associated with increased risk of developing ovarian cancer: RR = 1.57 (95% CI 1.11-2.22), P (trend) = 0.01. The association with wine intake at baseline was particularly strong among peri-/post-menopausal women who used estrogen-only hormone therapy and women of high socioeconomic status. CONCLUSIONS: Alcohol intake does not appear to affect ovarian cancer risk. Constituents of wine other than alcohol or, more likely, unmeasured determinants of wine drinking were associated with increased risk of ovarian cancer.

Hormone-related risk factors for breast cancer in women under age 50 years by estrogen and progesterone receptor status: results from a case-control and a case-case comparison.

INTRODUCTION: It has been suggested that hormonal risk factors act predominantly on estrogen receptor and progesterone receptor (ER/PR)-positive breast cancers. However, the data have been inconsistent, especially in younger women. METHODS: We evaluated the impact of age at menarche, pregnancy history, duration of breastfeeding, body mass index, combined oral contraceptive use, and alcohol consumption on breast cancer risk by ER/PR status in 1,725 population-based case patients and 440 control subjects aged 20 to 49 years identified within neighborhoods of case patients. We used multivariable unconditional logistic regression methods to conduct case-control comparisons overall as well as by ER/PR status of the cases, and to compare ER+PR+ with ER-PR- case patients. RESULTS: The number of full-term pregnancies was inversely associated with the risk of ER+PR+ breast cancer (ptrend = 0.005), whereas recent average alcohol consumption was associated with an increased risk of ER+PR+ breast cancer (ptrend = 0.03). Neither of these two factors was associated with the risk of ER- PR- breast cancer. Late age at menarche and a longer duration of breastfeeding were both associated with decreased breast cancer risk, irrespective of receptor status (all ptrend< or = 0.03). CONCLUSION: Our results suggest that the number of full-term pregnancies and recent alcohol consumption affect breast cancer risk in younger women predominantly through estrogen and progesterone mediated by their respective receptors. Late age at menarche and breastfeeding may act through different hormonal mechanisms.

Prediagnostic level of serum retinol in relation to reduced risk of hepatocellular carcinoma.

BACKGROUND: Retinol and its derivatives (retinoids), which have antioxidant activity and promote cell differentiation, may protect against the development of hepatocellular carcinoma (HCC) by controlling hepatocellular differentiation and reducing inflammatory responses. METHODS: We examined prospectively the relationship between prediagnostic serum concentrations of retinol, alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; and selenium and the risk of developing HCC among 213 patients with HCC and 1087 matched control subjects from a cohort of 18,244 men in Shanghai, China, who were monitored from 1986 through 2001. Odds ratios (ORs) and 95% confidence intervals (CIs) for men by quartile of serum concentrations of micronutrients were estimated by using logistic regression with adjustment for cigarette smoking status, alcohol intake, self-reported history of physician-diagnosed hepatitis or liver cirrhosis at recruitment, and seropositivity for hepatitis B surface antigen (HBsAg). All statistical tests were two-sided. RESULTS: Men with high prediagnostic serum retinol levels had a lower risk of HCC than men in the lowest quartile (Q2 versus Q1, OR = 0.37, 95% CI = 0.22 to 0.61; Q3 versus Q1, OR = 0.30, 95% CI = 0.17 to 0.50; and Q4 versus Q1, OR = 0.13, 95% CI = 0.06 to 0.26; Ptrend < .001). A statistically significant interaction was observed between retinol and HBsAg seropositivity on HCC risk; HBsAg-positive men in the lowest tertile of retinol had a greater than 70-fold higher risk (OR = 72.7, 95% CI = 31.6 to 167.4) of HCC than HBsAg-negative men in the highest tertile of retinol (Pinteraction = .018). No independent effect of serum levels of alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; or selenium on HCC risk were observed. CONCLUSION: High prediagnostic serum level of retinol is associated with a decreased risk of HCC in this population.

Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status.

BACKGROUND: Epidemiologic studies of the association between nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, and breast cancer risk have yielded inconsistent results. We investigated the association of NSAID use with risk of breast cancer in the California Teachers Study cohort, with special attention to risk of specific breast cancer subtypes and to type of NSAID used. METHODS: We analyzed data on 114 460 women in the California Teachers Study cohort who were aged 22 to 85 years and free of breast cancer at baseline in 1995 to 1996. Information on frequency and duration of NSAID use was collected through a self-administered questionnaire. A total of 2391 women were diagnosed with breast cancer during the follow-up period from 1995 to 2001. We used Cox proportional hazards regression to estimate relative risks (RR) and 95% confidence intervals (CI) of breast cancer subtypes with NSAID use. RESULTS: Neither regular use (more than once a week) of any NSAID (aspirin and ibuprofen combined) nor regular use of aspirin was associated with breast cancer risk (RR = 1.09, 95% CI = 0.97 to 1.21 for daily versus no regular use of NSAIDs and RR = 0.98, 95% CI = 0.86 to 1.13 for daily versus no regular use of aspirin). However, long-term (> or = 5 years) daily aspirin users had a non-statistically significant decreased risk of estrogen receptor and progesterone receptor (ER/PR)-positive breast cancer (RR = 0.80, 95% CI = 0.62 to 1.03). In contrast, we observed a statistically significantly increased risk of ER/PR-negative breast cancer with long-term daily use of aspirin (RR = 1.81, 95% CI = 1.12 to 2.92). In this population, 11 fewer ER/PR-positive breast cancer cases and seven excess ER/PR-negative breast cancer cases may be due to daily long-term aspirin use among 2391 breast cancer cases observed over 6 years if the association were proven to be causal. Long-term daily use of ibuprofen was also associated with an increased risk of breast cancer (RR = 1.51, 95% CI = 1.17 to 1.95), particularly of nonlocalized tumors (RR = 1.92, 95% CI = 1.24 to 2.97). If causality were subsequently proven, 16 of the observed 2391 breast cancer cases and 8 of the 713 non-localized breast cancer cases would be attributable to long-term daily use of ibuprofen. CONCLUSIONS: Long-term daily use of NSAIDs was not associated with breast cancer risk overall. Ibuprofen use was associated with an increased risk of breast cancer, and long-term daily aspirin use was associated with an increased risk of ER/PR-negative breast cancer. However, it is not clear if the observed association is causal.

Residential mobility in the California Teachers Study: implications for geographic differences in disease rates.

BACKGROUND: Especially for cancers with long latency periods, such as breast cancer, the issue of residential mobility hinders ecologic analyses seeking to examine the role of environmental contaminants in chronic disease etiology. This study describes and evaluates characteristics associated with residential mobility in a sub-sample of the California Teachers Study (CTS) cohort. METHODS: In 2000, lifetime residential histories were collected for a sub-sample of 328 women enrolled in the CTS; women's degree of residential mobility and associated factors were analyzed. RESULTS: While most women moved many times during their lives (average = 8.9), the average number of years at their residence when they enrolled in the study was reasonably long (15.1 years). Age strongly predicted duration at current residence but was not related to the number of lifetime residences. After adjusting for age, California-born women and women living in high socioeconomic status (SES) neighborhoods were significantly more residentially stable. Agreement between self-reported urbanization of recent residences and that based on census data of the geocoded residences was very good (80% concordant). Among women currently living in urban areas, an average of 43.3 years, or 77%, of their lifetimes were spent in urban residences; among women currently living in a rural area, an average of 37.3 years, or 67% of their lifetimes were spent in rural residences. CONCLUSIONS: This suggests that analyses of incidence rates based on current residence, while not capturing a woman's full exposure history, may reasonably reflect some aspect of longer term chronic exposures, especially those related to urbanization, at least in professional women.

Prescription drug use and risk of acute myeloid leukemia by French-American-British subtype: results from a Los Angeles County case-control study.

Chemotherapy is a well-established risk factor for acute myeloid leukemia (AML) but little is known about other prescription drugs and AML risk. We report data from a population-based Los Angeles County study in which 299 matched case-control pairs had complete data on prescription drug use and 88% of cases were subtyped according to the French-American-British (FAB) criteria. Cases were diagnosed between 1987 and 1994. Prescription nonsteroidal anti-inflammatory drug (NSAID) use for at least 4 weeks in the 2 to 10 years before diagnosis was associated with decreased risk (odds ratio = 0.5, 95% confidence interval=0.3, 1.0; p=0.04) with dose-response most evident for FAB subtype M2 (OR = 0.6, CI: 0.1, 2.9 for duration < or =6 months; OR = 0.2, CI: 0.0, 1.6 for >6 months). For subtype M4, ORs increased with increasing duration of benzodiazepine use in the 2 to 10 years before diagnosis (OR = 1.5, CI: 0.3, 9.0 for < or =6 months vs. OR = 5.0, CI: 0.6, 42.8 for >6 months). These results suggest that prescription drugs other than chemotherapy may have FAB subtype-specific effects on AML risk.

Prediagnostic levels of serum micronutrients in relation to risk of gastric cancer in Shanghai, China.

Data on blood levels of specific carotenoids and vitamins in relation to gastric cancer are scarce. Little is known about the relationship between prediagnostic serum levels of carotenoids other than beta-carotene and risk of gastric cancer especially in non-Western populations. Prediagnostic serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, retinol, alpha-tocopherol, gamma-tocopherol, and vitamin C were determined on 191 cases and 570 matched controls within a cohort of 18,244 middle-aged or older men in Shanghai, China, with a follow-up of 12 years. High serum levels of alpha-carotene, beta-carotene, and lycopene were significantly associated with reduced risk of developing gastric cancer (all Ps for trend /=3 drinks of alcohol per day; the odds ratios (95% confidence intervals) for the second, third, and fourth quartile categories were 0.69 (0.28-1.70), 0.36 (0.14-0.94), and 0.39 (0.15-0.98), respectively, compared with the lowest quartile of vitamin C (P for trend = 0.02). There were no statistically significant relationships of serum levels of beta-cryptoxanthin, lutein/zeaxanthin, retinol, alpha-tocopherol, and gamma-tocopherol with gastric cancer risk. The present study implicates that dietary carotenes, lycopene, and vitamin C are potential chemopreventive agents for gastric cancer in humans.

Alkylaniline-hemoglobin adducts and risk of non-smoking-related bladder cancer.

BACKGROUND: Some members of the arylamine family of compounds, specifically 4-aminobiphenyl (ABP), 2-naphthylamine, and benzidine, are established human bladder carcinogens. Cigarette smoking and use of permanent hair dye contribute substantially to current arylamine exposure. Low levels of 4-ABP exposure have been associated with non-smoking-related bladder cancer. Other arylamine compounds coming from as yet unidentified environmental sources may also be human bladder carcinogens. METHODS: We conducted a population-based case-control study in Los Angeles County, California, involving 298 case subjects with bladder cancer and 308 control subjects, who were matched on age, sex, race/ethnicity, and neighborhood of residence. In-person interviews provided information on tobacco smoking and other potential risk factors for bladder cancer. To assess arylamine exposure, levels of arylamine-hemoglobin adducts of nine selected alkylanilines (2,3-dimethylaniline [2,3-DMA], 2,4-DMA, 2,5-DMA, 2,6-DMA, 3,4-DMA, 3,5-DMA, 2-ethylaniline [2-EA], 3-EA, 4-EA) were measured in peripheral blood collected from study subjects. Analysis of covariance and conditional logistic regression methods were used to analyze the relationship between arylamine-hemoglobin adducts and bladder cancer risk. All statistical tests were two-sided. RESULTS: Levels of all arylamine-hemoglobin adducts, with the exception of 2,6-DMA, were higher in smokers than in nonsmokers, and levels of all arylamine-hemoglobin adducts were higher in case subjects than in control subjects. Arylamine-hemoglobin adducts of 2,6-DMA, 3,5-DMA, and 3-EA were all independently, statistically significantly (all P<.001) associated with bladder cancer risk after adjusting for cigarette smoking at the time of blood collection, lifetime smoking history, and other potential risk factors. These adducts were also independently associated with bladder cancer risk when only nonsmokers at time of blood draw were considered (highest quartile versus lowest quartile: 2,6-DMA, relative risk [RR] of bladder cancer = 8.1, 95% confidence interval [CI] = 3.6 to 18.0; 3,5-DMA, RR = 2.7, 95% CI = 1.2 to 6.0; 3-EA, RR = 4.3, 95% CI = 1.6 to 11.6). CONCLUSIONS: Diverse arylamine exposures are strongly associated with bladder cancer risk among nonsmokers. Because arylamines may account for a substantial proportion of bladder cancers among the general population, identification of environmental sources of these compounds is needed.

Regional variations in breast cancer among california teachers.

BACKGROUND: Observed regional differences in breast cancer incidence could provide valuable clues to the etiology of this disease. The pattern of historically higher breast cancer rates among residents of California's San Francisco Bay and Southern Coastal areas is evident in the disease experience among members of the California Teachers Study. This large cohort study has followed female professional school employees for cancer incidence since 1995 and has collected extensive information on breast cancer risk factors. METHODS: Between 1996 and 1999, invasive breast cancer was diagnosed in 1562 of the 115,611 cohort members who could be geocoded to a California address in 1995 and who had no previous breast cancer diagnosis. Adjusted hazard rate ratios (HRs) were estimated through multivariate Cox proportional hazards modeling. RESULTS: Rates were higher for cohort members in the San Francisco Bay area (HR = 1.22; 95% confidence interval = 1.06-1.40) and Southern Coastal area (1.16; 1.04-1.30) compared with those in the rest of California. The distributions of variables representing socioeconomic status, urbanization, and personal risk factors were consistent with higher risks for cohort members residing in the San Francisco Bay and Southern Coastal areas. Adjustment for these factors, however, did not explain regional differences in incidence, resulting in HRs that remained elevated for these 2 areas. CONCLUSION: Regional differences in breast cancer incidence in this large, well-defined cohort are not easily explained by known risk factors.

Dietary soy and increased risk of bladder cancer: a prospective cohort study of men in Shanghai, China.

To verify our previous finding of a positive association between dietary soy and bladder cancer risk, we examined the association in a second, geographically distinct prospective cohort of Chinese subjects, the Shanghai Cohort Study. Briefly, 18,244 men aged 45-64 years were recruited between January 1986 and September 1989. As of December 31, 2002, 61 incident bladder cancer cases were identified. Information on soy consumption was obtained through in-person interviews at baseline using a food frequency questionnaire. Cox proportional hazard regression methods were used to estimate relative risks (RR) and their corresponding 95% confidence intervals (CI), with adjustment for age (years) at baseline interview, level of education and other potential confounders. Compared to men consuming soy less than once a week, the RR (95% CI) for those who consumed soy 1-<3 times per week, 3-<7 times a week and daily were 2.05 (0.80-5.29), 2.45 (0.89-6.76) and 4.61 (1.57-13.51), respectively (p for trend = 0.004), after adjustment for age, cigarette smoking and level of education. The soy-bladder cancer risk associations in smokers and non-smokers were comparable. The soy-bladder cancer relationship became stronger when the analysis was restricted to subjects with 2 or more years of follow-up.

Correlates of active and passive smoking in the California Teachers Study cohort.

OBJECTIVES: These analyses were designed to describe characteristics associated with active and passive smoking in a large cohort of women in order to identify possible confounders of the relationship between smoking exposures and breast cancer risk. METHODS: Analyses were based on 1995 data collected from the California Teachers Study (CTS) and were restricted to those with complete and usable tobacco data (n = 128,174). Age-adjusted and race-adjusted odds ratios (OR) were generated by unconditional logistic regression. RESULTS: Compared with never smokers, both current and former smokers experienced menarche at an earlier age. Current and former smokers also were more likely than their never smoking counterparts to be nulliparous. Among parous women, current, but not former smokers were less likely than never smokers to have had their first child at an older age. Similarly, among never smokers, those exposed to household passive smoking experienced menarche at an earlier age, were more likely to be nulliparous, and among parous women, were less likely to have had their first child at an older age than never smokers not exposed to passive smoking. Greater alcohol consumption was strongly associated with both active and passive smoking exposures. Compared with never smokers, current smokers were less likely to take antioxidant supplements, whereas former smokers were more likely to take antioxidant supplements. Among never smokers, antioxidant use did not differ depending on passive smoking exposure. A number of other dietary correlates of active and passive smoking were identified. CONCLUSIONS: We identified a number of reproductive and dietary correlates to smoking exposures that underscore the need to adjust for such factors in an analysis of smoking and breast cancer and potentially other disease entities. Furthermore, these findings may suggest potential mechanisms underlying an association between breast cancer and smoking.

Carotenoids/vitamin C and smoking-related bladder cancer.

Previous epidemiological studies of fruit and vegetable intake and bladder cancer risk have yielded inconsistent results, especially with respect to the role of cigarette smoking as a possible modifier of the diet-bladder cancer association. A population-based case-control study was conducted in nonAsians of Los Angeles, California, which included 1,592 bladder cancer patients and an equal number of neighborhood controls matched to the index cases by sex, date of birth (within 5 years) and race between January 1, 1987 and April 30, 1996. Information on smoking, medical and medication history, and intake frequencies of food groups rich in preformed nitrosamines, vitamins A and C and various carotenoids, were collected through in-person, structured interviews. Beginning in January 1992, all case patients and their matched control subjects were asked for a blood sample donation at the end of the in-person interviews for measurements of 3- and 4-aminobiphenyl (ABP) hemoglobin adducts, and glutathione S-transferases M1/T1/P1 (GSTM1/T1/P1) and N-acetyltransferase-1 (NAT1) genotypes. Seven hundred seventy-one (74%) case patients and 775 (79%) control subjects consented to the blood donation requests. In addition, all case patients and matched control subjects were asked to donate an overnight urine specimen following caffeine consumption for measurements of cytochrome P4501A2 (CYP1A2) and N-acetyltransferase-2 (NAT2) phenotypes. Urine specimens were collected from 724 (69%) case patients and 689 (70%) control subjects. After adjustment for nondietary risk factors including cigarette smoking, there were strong inverse associations between bladder cancer risk and intake of dark-green vegetables [p value for linear trend (p) = 0.01], yellow-orange vegetables (p = 0.01), citrus fruits/juices (p = 0.002) and tomato products (p = 0.03). In terms of nutrients, bladder cancer risk was inversely associated with intake of both total carotenoids (p = 0.004) and vitamin C (p = 0.02). There was a close correlation (r = 0.58, p = 0.0001) between intakes of total carotenoids and vitamin C in study subjects. When both nutrients were included in a multivariate logistic regression model, only total carotenoids exhibited a residual effect that was of borderline statistical significance (p = 0.07 and p = 0.40 for total carotenoids and vitamin C, respectively). Cigarette smoking was a strong modifier of the observed dietary effects; these protective effects were confined largely to ever smokers and were stronger in current than ex-smokers. Smokers showed a statistically significant or borderline statistically significant decrease in 3- and 4-aminobiphenyl (ABP)-hemoglobin adduct level with increasing intake of carotenoids (p = 0.04 and 0.05, respectively). The protective effect of carotenoids on bladder cancer seemed to be influenced by NAT1 genotype, NAT2 phenotype and CYP1A2 phenotype; the association was mainly confined to subjects possessing the putative NAT1-rapid, NAT2-rapid and CYP1A2-rapid genotype/phenotype. The carotenoid-bladder cancer association was not affected by the GSTM1, GSTT1 and GSTP1 genotypes.