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Background: Obesity and the metabolic syndrome (MetS) have both been linked to increased risk of postmenopausal breast cancer; however, their relative contributions are poorly understood. Methods: We examined the association of metabolic phenotypes of obesity defined by presence of the MetS (yes and no) and body mass index (BMI; normal, overweight, obese) with risk of postmenopausal breast cancer in a prospective analysis of a cohort of postmenopausal women ( n ∼ 21,000) with baseline measurements of blood glucose, triglycerides, HDL-cholesterol, blood pressure, waist circumference, and BMI. Women were classified into 6 metabolic obesity phenotypes according to their BMI (18.5-<25.0, 25.0-<30.0, ≥30.0 kg/m 2 ) and presence of the MetS (≥3 of the following: waist circumference ≥88 cm, triglycerides ≥150 mg/dL, HDL-C <50 mg/dL, glucose ≥100 mg/dL, and systolic/diastolic blood pressure ≥130/85 mmHg or treatment for hypertension). HRs for incident breast cancer and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models. Results: Over 15 years of follow-up, 1,176 cases of invasive breast cancer were diagnosed. Obesity, regardless of metabolic health, was associated with increased risk of breast cancer. Being obese and metabolically unhealthy was associated with the highest risk: HR, 1.62; 95% CI, 1.33-1.96. These associations were stronger in women who had never used hormone therapy. Conclusions: Our findings suggest that both obesity and metabolic dysregulation are associated with breast cancer risk. Impact: Beyond BMI, metabolic health should be considered a clinically relevant and modifiable risk factor for breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1730-5. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Adiposity is an established risk factor for postmenopausal breast cancer. Recent data suggest that high insulin levels in overweight women may play a major role in this relationship, due to insulin's mitogenic/antiapoptotic activity. However, whether overweight women who are metabolically healthy (i.e., normal insulin sensitivity) have elevated risk of breast cancer is unknown. We investigated whether overweight women with normal insulin sensitivity [i.e., homeostasis model assessment of insulin resistance (HOMA-IR) index, or fasting insulin level, within the lowest quartile (q1)] have increased breast cancer risk. Subjects were incident breast cancer cases (N = 497) and a subcohort (N = 2,830) of Women's Health Initiative (WHI) participants with available fasting insulin and glucose levels. In multivariate Cox models, metabolically healthy overweight women, defined using HOMA-IR, were not at elevated risk of breast cancer compared with metabolically healthy normal weight women [HRHOMA-IR, 0.96; 95% confidence interval (CI), 0.64-1.42]. In contrast, the risk among women with high (q3-4) HOMA-IRs was elevated whether they were overweight (HRHOMA-IR, 1.76; 95% CI, 1.19-2.60) or normal weight (HRHOMA-IR, 1.80; 95% CI, 0.88-3.70). Similarly, using fasting insulin to define metabolic health, metabolically unhealthy women (insulin q3-4) were at higher risk of breast cancer regardless of whether they were normal weight (HRinsulin, 2.06; 95% CI, 1.01-4.22) or overweight (HRinsulin, 2.01; 95% CI, 1.35-2.99), whereas metabolically healthy overweight women did not have significantly increased risk of breast cancer (HRinsulin, 0.96; 95% CI, 0.64-1.42) relative to metabolically healthy normal weight women. Metabolic health (e.g., HOMA-IR or fasting insulin) may be more biologically relevant and more useful for breast cancer risk stratification than adiposity per se., (©2014 American Association for Cancer Research.)

Women with benign proliferative breast disease (BPBD) are at increased risk for developing breast cancer. Evidence suggests that accumulation of adipose tissue can influence breast cancer development via hyperinsulinemia, increased estrogen, and/or inflammation. However, there are limited data investigating these pathways with respect to risk of BPBD. We evaluated serologic markers from these pathways in a case-control study of postmenopausal women nested within the Women's Health Initiative Clinical Trial. Cases were the 667 women who developed BPBD during follow-up, and they were matched to 1,321 controls. Levels of insulin, estradiol, C-reactive protein (CRP), and adiponectin were measured in fasting serum collected at baseline. Conditional logistic regression models were used to estimate ORs for the association of each factor with BPBD risk. Among nonusers of hormone therapy, fasting serum insulin was associated with a statistically significant increase in risk of BPBD (OR for highest vs. lowest quartile = 1.80; 95% confidence interval, CI, 1.16-2.79; Ptrend = 0.003) as were levels of estradiol (OR for highest vs. lowest tertile = 1.89; 95% CI, 1.26-2.83; Ptrend = 0.02) and CRP (OR for highest vs. lowest quartile = 2.46; 95% CI, 1.59-3.80; Ptrend < 0.001). Baseline adiponectin level was inversely associated with BPBD risk (OR for highest vs. lowest quartile = 0.47; 95% CI, 0.31-0.71; Ptrend < 0.001). These associations persisted after mutual adjustment, but were not observed among users of either estrogen alone or of estrogen plus progestin hormone therapy. Our results indicate that serum levels of estrogen, insulin, CRP, and adiponectin are independent risk factors for BPBD and suggest that the estrogen, insulin, and inflammation pathways are associated with the early stages of breast cancer development., (©2014 American Association for Cancer Research.)

Background: Prospective studies in Western and Asian populations suggest that height is a risk factor for various cancers. However, few studies have explored potential confounding or effect modification of the association by other factors., Methods: We examined the association between height measured at enrollment in 144,701 women participating in the Women's Health Initiative and risk of all cancers combined and cancer at 19 specific sites. Over a median follow-up of 12.0 years, 20,928 incident cancers were identified. We used Cox proportional hazards models to estimate HR and 95% confidence intervals (CI) per 10 cm increase in height, with adjustment for established risk factors. We also examined potential effect modification of the association with all cancer and specific cancers., Results: Height was significantly positively associated with risk of all cancers (HR = 1.13; 95% CI, 1.11-1.16), as well as with cancers of the thyroid, rectum, kidney, endometrium, colorectum, colon, ovary, and breast, and with multiple myeloma and melanoma (range of HRs: 1.13 for breast cancer to 1.29 for multiple myeloma and thyroid cancer). These associations were generally insensitive to adjustment for confounders, and there was little evidence of effect modification., Conclusions: This study confirms the positive association of height with risk of all cancers and a substantial number of cancer sites., Impact: Identification of single-nucleotide polymorphisms associated both with height and with increased cancer risk may help elucidate the association., (©2013 AACR)

Background: Aside from exposure to ionizing radiation and benzene, little is known about lifestyle risk factors for chronic myeloid leukemia (CML) in the general population., Methods: We examined the relation between lifestyle and dietary risk factors for CML in 493,188 participants (294,271 males and 198,917 females) aged 50 to 71 years who completed a baseline questionnaire in the National Institutes of Health-AARP Diet and Health Study in 1995 to 1996. Over a median of 10.5 years of follow-up, 178 incident cases of CML (139 males and 39 females) were ascertained from state registries. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for exposures of interest, adjusting for potential confounding variables., Results: In multivariable analysis of all participants combined, female sex, years of education, and vigorous physical activity (HR for ≥3 times/week vs. <1 time/week 0.70; 95% CI, 0.49-0.99) were inversely associated with risk of CML, whereas smoking intensity (HR for smokers of ≥20 cigarettes per day vs. never smokers: 1.53; 95% CI, 1.03-2.27) and body mass (HR for BMI ≥ 30 vs. <25 kg/m(2) 1.46; 95% CI, 0.95-2.23) were associated with increased risk. A range of dietary factors was not associated with disease., Conclusions: This study adds to the sparse information about lifestyle factors, which affect the risk of CML in the general population., Impact: If these findings are confirmed, it would suggest that CML may be amenable to preventive strategies.

Background: Triple-negative breast cancer, characterized by a lack of hormone receptor and HER2 expression, is associated with a particularly poor prognosis. Focusing on potentially modifiable breast cancer risk factors, we examined the relationship between body size, physical activity, and triple-negative disease risk., Methods: Using data from 155,723 women enrolled in the Women's Health Initiative (median follow-up, 7.9 years), we assessed associations between baseline body mass index (BMI), BMI in earlier adulthood, waist and hip circumference, waist-hip ratio, recreational physical activity, and risk of triple-negative (n=307) and estrogen receptor-positive (ER+, n=2,610) breast cancers., Results: Women in the highest versus lowest BMI quartile had 1.35-fold (95% CI, 0.92-1.99) and 1.39-fold (95% CI, 1.22-1.58) increased risks of triple-negative and ER+ breast cancers, respectively. Waist and hip circumferences were positively associated with risk of ER+ breast cancer (Ptrend=0.01 for both measures) but were not associated with triple-negative breast cancer. Compared with women who reported no recreational physical activity, women in the highest activity tertile had similarly lower risks of triple-negative and ER+ breast cancers (HR=0.77; 95% CI, 0.51-1.13; and HR=0.85; 95% CI, 0.74-0.98, respectively)., Conclusions: Despite biological and clinical differences, triple-negative and ER+ breast cancers are similarly associated with BMI and recreational physical activity in postmenopausal women. The biological mechanisms underlying these similarities are uncertain and these modest associations require further investigation., Impact: If confirmed, these results suggest potential ways postmenopausal women might modify their risk of both ER+ and triple-negative breast cancers., (©2011 AACR.)

Gliomas are the most common type of primary malignant brain tumor and have a very poor prognosis. Little is known, however, about the etiology of these tumors. Evidence from a number of sources suggests that endogenous steroid hormones may play a role in the development of gliomas. First, the descriptive epidemiology of glioma suggests a relative protection of females compared with males, particularly during the premenopausal years. Second, some gliomas and glioblastomas express estrogen receptors (ER), especially ERβ, as well as aromatase, the enzyme responsible for the conversion of testosterone to estradiol, and possibly other steroid hormone receptors. Third, experimental studies indicate that glioblastomas transplanted into animals grow at a slower rate in females compared with males. Finally, experimental studies show that estradiol, 2-methoxyestradiol, and a number of selective estrogen receptor modulators inhibit proliferation of gliomas and induce cell death. These hormonal agonists and antagonists may act either through classical steroid hormone receptors or independently of such receptors. In view of these findings, further clinical, experimental, and epidemiologic studies are needed to elucidate the role of steroid hormone agonists and antagonists in the development and proliferation of glioma. If hormonal pathways are involved in gliomagenesis, this could eventually lead to the design of preventive strategies., (©2010 AACR.)

Background: Observational studies have commonly linked higher alcohol consumption with a modest increase in invasive breast cancer risk, but cohort studies have not examined alcohol intake in relation to ductal carcinoma in situ (DCIS)., Methods: The association between adulthood alcohol consumption assessed at baseline and subsequent DCIS risk was examined in a cohort of postmenopausal women participating in the Women's Health Initiative clinical trials, in which mammography was protocol-mandated. Alcohol intake was assessed by a semiquantitative food-frequency questionnaire. Reported DCIS cases were verified by central pathology report review. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals., Results: The cohort consisted of 63,822 women with information on alcohol intake, among whom 489 cases of DCIS were ascertained after a median follow-up of 8.0 years. For the primary analysis, invasive breast cancer was treated as a competing risk, and follow-up time was censored at the date of diagnosis of invasive breast cancer. After adjustment for covariates, the hazard ratio for DCIS among women who consumed 14 or more servings of alcohol per week, relative to nondrinkers, was 0.87 (95% confidence interval, 0.50-1.51). In addition, alcohol intake was not associated with risk of either high-grade or low-/moderate-grade DCIS., Conclusions: In this large cohort study of postmenopausal women, alcohol consumption was not associated with risk of DCIS., Impact: If other studies confirm our findings, this would suggest that alcohol may have an effect later in the carcinogenic process., ((c)2010 AACR.)

The metabolic syndrome, characterized by abdominal obesity, high blood glucose levels, impaired glucose tolerance, dyslipidemia, and hypertension, is associated with increased risk of type 2 diabetes and coronary heart disease. Several studies have examined the association of the individual components of the metabolic syndrome with breast cancer; to date, however, no study has assessed the metabolic syndrome per se in relation to breast cancer risk. Furthermore, previous studies have relied only on baseline assessment of components of the syndrome. Therefore, we assessed the association of the metabolic syndrome with the risk of postmenopausal breast cancer among women in the 6% sample of subjects in the Women's Health Initiative clinical trial and the 1% sample of women in the observational study who had repeated measurements of the components of the syndrome during follow-up. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association of breast cancer risk with the presence of the metabolic syndrome, as well as its components, at baseline and in time-dependent analyses. After exclusion of women with diabetes, among 4,888 women with baseline measurements, 165 incident cases of breast cancer were ascertained over a median of 8 years of follow-up. The presence of the metabolic syndrome at baseline was not associated with altered risk. Of the individual components measured at baseline, diastolic blood pressure showed a borderline positive association with breast cancer. In time-dependent covariate analyses, however, certain scenarios indicated a positive association between the metabolic syndrome and breast cancer, due primarily to positive associations with serum glucose, serum triglycerides, and diastolic blood pressure.

Background: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival., Methods: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n=1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n=173 deaths) and breast cancer-specific mortality (n=113 deaths) were determined through the National Death Index., Results: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only., Conclusion: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings.

Recent studies suggest that elevated body iron levels may contribute to breast carcinogenesis; however, epidemiologic evidence is lacking. We used data from a large cohort study of Canadian women to assess breast cancer in association with total iron and heme iron intake. Among 49,654 women ages 40 to 59 followed for an average of 16.4 years, we identified 2,545 incident breast cancer cases. Data from a food frequency questionnaire administered at baseline were used to calculate total dietary iron and heme iron intake. Using Cox proportional hazards models, we found no association of iron or heme iron intake with risk of breast cancer overall, in women consuming 30+ g of alcohol per day, or in women who had ever used hormone replacement therapy. The present study offers no support for an association of iron or heme iron intake with breast cancer risk or for a modification by iron of the effect of alcohol or estrogen. However, further cohort studies with repeated measurement of iron intake are warranted.

Accumulating evidence from epidemiologic studies suggests that risk of breast cancer is reduced in relation to increased consumption of folate and related B vitamins. We investigated independent and joint effects of B vitamin intake as well as two polymorphisms of a key one-carbon metabolizing gene [i.e., methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C] on breast cancer risk. The study uses the resources of a population-based case-control study, which includes 1,481 cases and 1,518 controls. Significant inverse associations between B vitamin intake and breast cancer risk were observed among non-supplement users. The greatest reduction in breast cancer risk was observed among non-supplement users in the highest quintile of dietary folate intake [odds ratio (OR), 0.61; 95% confidence interval (95% CI), 0.41-0.93] as compared with non-supplement users in the lowest quintile of dietary folate intake (high-risk individuals). The MTHFR 677T variant allele was associated with increased risk of breast cancer (P, trend = 0.03) with a multivariate-adjusted OR of 1.37 (95% CI, 1.06-1.78) for the 677TT genotype. The 1298C variant allele was inversely associated with breast cancer risk (P, trend = 0.03), and was likely due to the linkage of this allele to the low-risk allele of 677C. The MTHFR-breast cancer associations were more prominent among women who did not use multivitamin supplements. Compared with 677CC individuals with high folate intake, elevation of breast cancer risk was most pronounced among 677TT women who consumed the lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate intake (OR, 1.71; 95% CI, 1.08-2.71). From a public heath perspective, it is important to identify risk factors, such as low B vitamin consumption, that may guide an effective prevention strategy against the disease.

Whether fruit, vegetable, and antioxidant micronutrient consumption is associated with a reduction in breast cancer incidence remains unresolved. To address this issue, we analyzed data from a large population-based case-control study, with consideration given to whether the associations varied with menopausal status or with clinical characteristics of the cases' disease. Study participants completed a modified Block food frequency questionnaire, which included assessment of the frequency and portion sizes of 13 fruits and fruit juices and 16 vegetables and the use of multiple and single vitamin supplements. Statistical analyses were done on 1,463 cases and 1,500 controls. Among postmenopausal women, reduced odds ratios [OR; 95% confidence intervals (95% CI)] were noted for the highest fifth, as compared with the lowest fifth, of intake of any vegetables [0.63 (0.46-0.86); P for trend < 0.01] and leafy vegetables [0.66 (0.50-0.86); P for trend = 0.03] after controlling for age and energy intake. Adjusted ORs (95% CIs) were also decreased for postmenopausal breast cancer in relation to high intake of carotenoids, alpha-carotene, beta-carotene, lutein, and particularly lycopene [0.66 (0.48-0.90); P for trend = 0.03]. Inverse associations for fruits and vegetables were stronger for postmenopausal women with estrogen receptor (ER)+ tumors (OR, 0.65; 95% CI, 0.51-0.82) than ER- tumors (OR, 0.92; 95% CI, 0.64-1.32), but results were less consistent for micronutrients. No similarly reduced associations were observed among premenopausal women. ORs did not appreciably differ by in situ or invasive breast cancer or by whether cases had begun chemotherapy. Our results support an inverse association for fruit and vegetable intake among postmenopausal but not premenopausal breast cancer, which may be more pronounced among women with ER+ tumors.

Polycyclic aromatic hydrocarbons (PAH) are potent mammary carcinogens in rodents, but their effect on breast cancer development in women is not clear. To examine whether currently measurable PAH damage to DNA increases breast cancer risk, a population-based case-control study was undertaken on Long Island, NY. Cases were women newly diagnosed with in situ and invasive breast cancer; controls were randomly selected women frequency matched to the age distribution of cases. Blood samples were donated by 1102 (73.0%) and 1141 (73.3%) of case and control respondents, respectively. Samples from 576 cases and 427 controls were assayed for PAH-DNA adducts using an ELISA. The geometric mean (and geometric SD) of the log-transformed levels of PAH-DNA adducts on a natural scale was slightly, but nonsignificantly, higher among cases [7.36 (7.29)] than among controls [6.21 (4.17); P = 0.51]. The age-adjusted odds ratio (OR) for breast cancer in relation to the highest quintile of adduct levels compared with the lowest was 1.51 [95% confidence interval (CI), 1.04-2.20], with little or no evidence of substantial confounding (corresponding multivariate-adjusted OR, 1.49; 95% CI, 1.00-2.21). There was no consistent elevation in risk with increasing adduct levels, nor was there a consistent association between adduct levels and two of the main sources of PAH, active or passive cigarette smoking or consumption of grilled and smoked foods. These data indicate that PAH-DNA adduct formation may influence breast cancer development, although the association does not appear to be dose dependent and may have a threshold effect.

Whether environmental contaminants increase breast cancer risk among women on Long Island, NY, is unknown. The study objective is to determine whether breast cancer risk is increased in relation to organochlorines, compounds with known estrogenic characteristics that were extensively used on Long Island and other areas of the United States. Recent reports do not support a strong association, although there are concerns with high risks observed in subgroups of women. Blood samples from 646 case and 429 control women from a population-based case-control study conducted on Long Island were analyzed. No substantial elevation in breast cancer risk was observed in relation to the highest quintile of lipid-adjusted serum levels of p,p'-bis(4-chlorophenyl)-1,1-dichloroethene (DDE) [odds ratio (OR), 1.20 versus lowest quintile; 95% confidence interval (CI), 0.76-1.90], chlordane (OR, 0.98; 95% CI, 0.62-1.55), dieldrin (OR, 1.37; 95% CI, 0.69-2.72), the sum of the four most frequently occurring PCB congeners (nos. 118, 153, 138, and 180; OR, 0.83; 95% CI, 0.54-1.29), and other PCB congener groupings. No dose-response relations were apparent. Nor was risk increased in relation to organochlorines among women who had not breastfed or were overweight, postmenopausal, or long-term residents of Long Island; or with whether the case was diagnosed with invasive rather than in situ disease, or with a hormone receptor-positive tumor. These findings, based on the largest number of samples analyzed to date among primarily white women, do not support the hypothesis that organochlorines increase breast cancer risk among Long Island women.

Preliminary studies suggest that the estrogen metabolite 16 alpha-hydroxyestrone is associated with breast cancer, whereas 2-hydroxyestrone is not. However, epidemiological studies evaluating this relationship and taking established risk factors for breast cancer into account are lacking. The purpose of this study was to examine the association of the ratio of the urinary estrogen metabolites (2-hydroxyestrone and 16 alpha-hydroxyestrone) and of the individual metabolites with breast cancer. A spot urine sample, a brief history, and clinical data were collected from breast cancer cases (n = 42) and from women coming to the hospital for a routine mammogram or attending a free breast cancer screening (n = 64). 2-Hydroxyestrone and 16 alpha-hydroxyestrone were measured by enzyme immunoassay, and the estrogen metabolite ratio (EMR; 2-hydroxyestrone:16 alpha-hydroxyestrone) was computed. Cases and controls were similar in terms of age (mean age of cases, 53.8 +/- 15.1 years, versus 54.2 +/- 10.4 years for controls; P = 0.9) and demographics. Mean EMR was not associated with breast cancer overall (1.67 +/- 0.80 versus 1.72 +/- 0.66; P = 0.7). However, in postmenopausal women, the mean EMR was significantly lower in cases compared to controls (1.41 +/- 0.73 versus 1.81 +/- 0.71; P = 0.05). The multivariate adjusted odds ratios for the intermediate and lowest tertiles of the EMR relative to the highest among postmenopausal women were 9.73 (95% confidence interval, 1.27-74.84) and 32.74 (95% confidence interval, 3.36-319.09), respectively. The test for trend was highly significant (P = 0.003). Analyses of the individual metabolites indicated that 16 alpha-hydroxyestrone was a strong risk factor. The EMR did not show any consistent associations with age, race/ethnicity, age at first birth, parity, body mass index, family history of breast cancer, smoking, or alcohol intake. These data suggest a strong, inverse association of the EMR and a strong positive association of 16 alpha-hydroxyestrone with breast cancer in postmenopausal women. Larger studies are needed to confirm these results and to assess the relationship of the EMR and of the individual metabolites with breast cancer, with attention to menopausal status and clinical factors and with adjustment for known breast cancer risk factors.

Black males have higher age-adjusted lung cancer incidence rates compared to white males, and blacks of both sexes have higher rates of increase in lung cancer incidence over past decades. The majority of black smokers smoke mentholated cigarettes. These observations prompted us to assess the effect of smoking mentholated cigarettes on lung cancer risk, using data from a hospital-based case-control study of tobacco-related cancers. Analysis was restricted to current cigarette smokers and was carried out on 588 male lung cancer cases and 914 male control patients and on 456 female lung cancer cases and 410 female controls interviewed between 1985 and 1990. The prevalence of menthol usage did not differ between cases and controls of either sex. No significant association was observed between either short-term (1-14 years) or long-term (15+ years) menthol use and lung cancer in logistic regression analyses adjusting for covariates. For specific histological types of lung cancer there was no indication of an association with menthol usage.

The importance of smoking-related variables in the development of bladder cancer was examined in data from a hospital-based case-control study of 1316 male and 505 female cases, and 3940 male and 1504 female age-matched controls interviewed in 20 hospitals from 9 United States cities between 1969 and 1984. For male current smokers, odds ratios for number of cigarettes smoked per day (cpd) increased to approximately 2.5 for smokers of more than 20 cpd, after adjustment for duration and nonsmoking-related covariates. Above 20 cpd, no further increase in odds ratio was observed. In females, the adjusted odds ratios showed no significant effect of increasing cpd level. In males, the odds ratios for duration increased from 1.18 (0.52-2.72) in those who smoke for less than 20 years to 2.31 (1.65-3.24) in those who smoked for greater than 40 years. In females, the corresponding odds ratios were 0.97 (0.27-3.44) and 1.62 (1.00-2.62). The results did not suggest an increased risk with early age at start of smoking in either sex. Ex-cigarette smokers, as a whole, had reduced odds ratios for bladder cancer, but the extent of the reduction was similar in short-term and longer-term quitters. The findings of this investigations support an association between smoking and bladder cancer. The pattern of risk associated with cpd and duration among current smokers and the early decline in risk associated with quitting are discussed in relation to possible mechanisms of bladder carcinogenesis.

Interviews were obtained from 125 women with oral cavity cancer and 107 female controls to assess the role of mouthwash use as a risk factor for oral cancer in women. In addition to detailed information on mouthwash use throughout adult life, information was obtained regarding smoking, alcohol consumption, general oral hygiene practices, and occurrence of nonmalignant conditions of the oral cavity. Mouthwash use was not associated with increased oral cancer risk in terms of frequency, duration of use, dilution, or rinsing practices. Among mouthwash users, cases reported taking more mouthfuls of mouthwash at each use compared with controls. Again among mouthwash users, cases were significantly more likely than controls to give as a reason for using mouthwash "to disguise the smell of tobacco" and "to disguise the smell of alcohol," whereas similar proportions of cases and controls reported using mouthwash to "disguise the smell of onions, garlic, etc." and "to disguise breath odors due to mouth infections or dental problems." These first two reasons for using mouthwash were strongly associated with smoking and drinking, respectively, and appear to be proxies for these exposures. Smoking, drinking, having 10 or more missing teeth, and religious background (non-Jewish versus Jewish) were significantly associated with oral cancer.