Contraception methods, beyond oral contraceptives and tubal ligation, and risk of ovarian cancer.

PURPOSE: Few studies have examined methods of contraception, beyond oral contraceptives (OCs) and tubal ligation, in relation to ovarian cancer risk. METHODS: Nine hundred two cases with incident ovarian/peritoneal/tubal cancer were compared with 1800 population-based control subjects. Women self-reported all methods of contraception by using life calendars. RESULTS: Each of the contraceptive methods examined reduced the risk of ovarian cancer as compared with use of no artificial contraception. Comparing ever versus never use, after adjustment for potentially confounding factors and all other methods of contraception, the methods of contraception that emerged as protective were OCs (adjusted odds ratio [adj OR] 0.75, 95% confidence interval [CI] 0.61-0.93); tubal ligation (adj OR 0.63, 95% CI 0.51-0.77); intrauterine devices (IUDs) (adj OR 0.75, 95% CI 0.59-0.95); and vasectomy (adj OR 0.77, 95% CI 0.61-0.99). Although for OCs and tubal ligation we found that the longer the duration of use, the greater the effect, for IUDs the pattern was reversed: significant protection occurred with short duration and progressively greater risk (albeit nonsignificant) was seen with longer duration of use. CONCLUSIONS: In the largest case-control study to date, a range of effective methods of contraception reduced the risk for ovarian cancer. OCs and tubal ligation reduced ovarian cancer risk with lower odds ratios with longer duration of use, whereas IUDs reduced risk overall, having the greatest impact with short duration of use.

Bile constituents in hibernating golden-mantled ground squirrels (Spermophilus lateralis).

BACKGROUND: Golden-mantled ground squirrels (S. lateralis) are anorexic during the winter and survive by exploiting hibernation to reduce energetic demands. The liver normally plays a critical role in fueling and regulating metabolism and one might expect significant changes in hepatobiliary function with hibernation. We analyzed bile collected from animals in summer, animals in winter that were either torpid, active between bouts of torpor, or which failed to enter hibernation in order to characterize the effects of hibernation on hepatobiliary function per se. RESULTS: Surprisingly, hibernator bile did not differ from summer squirrel bile in key characteristics including [bile acids], [cholesterol], [free fatty acids], [lecithin], and osmolality. One major distinction between summer and winter squirrels was that winter squirrels experience >5 fold increases in [bilirubin]. Such an increase may have significant physiological consequences that could aid in survivorship of torpor. Animals that failed to hibernate, despite being anorexic, were very similar to summer squirrels in all measured parameters except they had lower bile acid and lecithin concentrations. CONCLUSION: The data indicate that despite extended anorexia, differences in metabolic fuel privation, and bouts of reduced body temperatures, hibernators normally do not experience broad changes in hepatobiliary function.

Use of common medications and breast cancer risk.

Prescription and over-the-counter medications are widely used in the United States and many western countries. More than two-thirds of women ages >45 years, who are at greatest risk for breast cancer, take prescription medication. In light of the ubiquitous nature of medication use and the fact that breast cancer remains the most common cancer in women, research on the role of medication use in breast cancer etiology is warranted. We summarize the epidemiologic evidence on the association between breast cancer risk and use of common medications, including antibiotics, antidepressants, statins, antihypertensives, and nonsteroidal anti-inflammatory drugs. Overall, there is little evidence that would implicate the use of antibiotics, antidepressants, statins, and antihypertensives in the etiology of breast cancer. Although several prospective studies and a randomized low-dose aspirin chemoprevention trial have not shown lower risk of breast cancer among aspirin users, most studies that have examined the potential chemoprotective effect of nonsteroidal anti-inflammatory drugs have shown significant risk reductions for regular and prolonged use of these drugs. The existing literature on the role of medication use in breast carcinogenesis is complicated. Interpretation of the evidence is hampered due to major methodologic differences across studies, including exposure assessment, exposure classification, and adjustment for potential confounding variables. These differences largely stem from the fact that the majority of articles on this topic represent secondary data analyses from studies with inadequate information on exposure or confounders. Thus, future epidemiologic studies specifically designed to study these ubiquitous and biologically plausible exposures are warranted.

Acute myeloid leukemia and myelodysplastic syndrome following breast cancer: increased frequency of other cancers and of cancers in multiple family members.

Adjuvant chemotherapy and radiation therapy for breast cancer are associated with therapy-related acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS), but little is known about additional risk factors. Thirty-four patients with AML (n=26)/MDS (n=8) following breast cancer (cases) were compared with 2029 breast cancer patients without AML/MDS (controls). Cases were older at breast cancer diagnosis (mean 60.2 years versus 54.5 years; p=0.01) and more commonly had additional cancers (29% versus 4.9%; p<0.0001) and >or=4 first-degree relatives with any type of cancer (OR: 5.37, CI: 1.44-19.9). Thus risk factors for AML/MDS following breast cancer include older age, other cancers and multiple first-degree relatives with cancer.

Dietary intakes of selected nutrients and food groups and risk of cervical cancer.

We investigated the relationships between intakes of selected dietary nutrients and food groups and risk of cervical cancer in a hospital-based, case-control study including 239 cases diagnosed with squamous cell carcinoma of the cervix and 979 hospital patients with nonneoplastic diagnoses who completed a self-administered questionnaire between 1982 and 1998 at Roswell Park Cancer Institute. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusting for age, education, smoking status, use of oral contraceptives, barrier contraceptives and spermicides, family history of cervical cancer, year questionnaire completed, and energy intake. Significant reductions in risk of approximately 40-60% were observed for women in the highest vs. lowest tertiles of dietary fiber (OR=0.59, 95% CI=0.37-0.94), vitamin C (OR=0.52, 95% CI=0.33-0.80), vitamin E (OR=0.44, 95% CI=0.27-0.72), vitamin A (OR=0.47, 95% CI=0.30-0.73), alpha-carotene (OR=0.41, 95% CI=0.27-0.63), beta-carotene (OR=0.44, 95% CI=0.29-0.68), lutein (OR=0.51, 95% CI=0.33-0.79), folate (OR=0.55, 95% CI=0.34-0.88), and total fruit and vegetable intake (OR=0.52, 95% CI=0.34-0.77). Our findings suggest that a diet rich in plant-based nutrients may be important in reducing the risk of cervical cancer.

Regular analgesic use and risk of multiple myeloma.

Analgesic use has been implicated in the chemoprevention of a number of solid tumors, but to date no previous research has focused on the role of analgesics in the etiology of multiple myeloma (MM). We conducted a hospital-based case-control study of 117 patients with primary, incident MM and 483 age and residence matched controls without benign or malignant neoplasms. All participants received medical services at Roswell Park Cancer Institute in Buffalo, NY, and completed a comprehensive epidemiological questionnaire. Participants who reported analgesic use at least once a week for at least 6 months were classified as regular users; individuals who did not use analgesics regularly served as the reference group throughout the analyses. We used unconditional logistic regression analyses to compute crude and adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Compared to non-users, regular aspirin users were not at reduced risk of MM (adjusted OR=0.99; 95% CI 0.65-1.49), nor were participants with the highest frequency or duration of aspirin use. A significant risk elevation was found for participants who were regular acetaminophen users (adjusted OR=2.95; 95% CI 1.72-5.08). Further, marked increases in risk of MM were noted with both greater frequency (>7 tablets weekly; adjusted OR=4.36; 95% CI 1.70-11.2) and greater duration (>10 years; adjusted OR=3.26; 95% CI 1.52-7.02) of acetaminophen use. We observed no evidence of a chemoprotective effect of aspirin on MM risk, but observed significant risk elevations with various measures of acetaminophen use. Our results warrant further investigation in population-based case-control and cohort studies and should be interpreted with caution in light of the limited sample size and biases inherent in hospital-based studies.

Risk of ovarian cancer associated with BMI varies by menopausal status.

Obesity has been linked to increased risk of several malignancies, but the role of obesity in the etiology of ovarian cancer remains unclear. Therefore, a hospital-based case-control study was conducted to investigate the association between body size and risk of ovarian cancer. Participants included 427 women with primary, incident ovarian cancer and 854 cancer-free controls. All participants received medical services at Roswell Park Cancer Institute in Buffalo, NY between 1982 and 1998 and completed a comprehensive epidemiological questionnaire. The instrument included questions regarding height and usual wt prior to survey. Participants were classified as underweight/normal (BMI < or = 24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), or obese (BMI > or = 30.0 kg/m2). Compared with underweight/normal participants, being overweight (adjusted odds ratio [OR] = 1.02; 95% CI 0.77-1.36) or obese (adjusted OR = 1.17; 95% CI 0.84-1.65) was not significantly associated with an elevated risk of ovarian cancer. After stratification by menopausal status, BMI showed no significant association to ovarian cancer risk among postmenopausal women (> or = 50 y old). However, among premenopausal women (<50 y old), those classified as obese had a significantly increased risk (adjusted OR = 2.19; 95% CI 1.19-4.04) compared with women classified as normal/underweight. These findings suggest a potential influence of menopausal status on the total endogenous hormonal environment, including estrogens, androgens, and insulin-like growth factors, when considering the association between body size and ovarian cancer risk. In light of the fact that obesity is a modifiable risk factor, further investigation on this topic is warranted.

Regular aspirin use and esophageal cancer risk.

Given the high mortality rate and the rapidly increasing incidence rate of esophageal carcinoma, chemopreventive agents are highly desirable. Aspirin has been shown to be associated with reduced risk of developing colorectal carcinoma and other cancers. Even though previous studies have shown reduced risk of esophageal cancer associated with aspirin use, results were inconsistent with respect to frequency and duration of use. In this hospital-based case-control study, 163 esophageal cancer cases were compared to 482 age- and sex-matched hospital controls with nonneoplastic conditions. Participants were classified as regular aspirin users if they had taken the drug at least once a week for 6 months. Results suggest that esophageal cancer risk is significantly lower for regular aspirin users compared to nonusers [adjusted odds ratio (aOR) 0.54; 95% confidence interval (CI) 0.36-0.86]. Individuals who used an equivalent of at least 1 aspirin a day (> or =7 tablets/week) were half as likely to have been diagnosed with esophageal carcinoma (aOR 0.47; 95% CI 0.26-0.85), and a linear trend was noted with increasing frequency of use (p(trend) 0.007). Similar protective effects were noted with < or =20 years of use, whereas no risk reduction was noted with >20 years of use. Consistent reduction in risk associated with aspirin use was noted among both the major histological subtypes, but the protective effect appears to be more pronounced in adenocarcinoma compared to squamous cell carcinoma. Overall, results from the current study suggest that regular aspirin use may be associated with reduced risk of esophageal cancer.

Consumption of coffee, but not black tea, is associated with decreased risk of premenopausal breast cancer.

Caffeine has been suggested as a possible risk factor for breast cancer, potentially through its effect of facilitating the development of benign breast disease. However, coffee and tea also contain polyphenols, which exhibit anticarcinogenic properties. A hospital-based, case-control study was conducted to evaluate the role of coffee, decaffeinated coffee, and black tea in breast cancer etiology. Study participants included 1932 cases with primary, incident breast cancer and 1895 hospital controls with nonneoplastic conditions. All participants completed a comprehensive epidemiological questionnaire. Among premenopausal women, consumption of regular coffee was associated with linear declines in breast cancer risk (P for trend = 0.03); consumers of >or=4 cups/d experienced a 40% risk reduction (odds ratio = 0.62, 95% CI 0.39-0.98). No clear associations between intake of black tea or decaffeinated coffee and breast cancer risk were noted among premenopausal women, although black tea was associated with a protective effect unique to a subsample of cases with lobular histology. Among postmenopausal women, breast cancer risk was not associated with consumption of coffee, tea, or decaffeinated coffee. Results among postmenopausal women did not differ by histologic subtype. Our findings support a protective effect of coffee intake on premenopausal, but not postmenopausal breast cancer risk. Further studies are warranted to confirm these findings.

Opposing effects of aspirin and acetaminophen use on risk of adult acute leukemia.

Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of hematologic cancer, although previous results have been inconsistent. The current study investigated the effects of aspirin or acetaminophen use on adult acute leukemia risk among 169 individuals with leukemia and 676 age and sex matched hospital controls with non-neoplastic conditions who completed a comprehensive epidemiologic questionnaire. Results indicate that regular aspirin use may be associated with a modest decrease in leukemia risk [adjusted odds ratio (aOR), 0.84; 95% confidence interval (CI), 0.59-1.21]. In contrast, ever using acetaminophen was associated with elevated leukemia risk (aOR, 1.53; 95% CI, 1.03-2.26). Results did not differ between men and women. Other studies have demonstrated that acetaminophen is associated with transient decreases in DNA repair, and lymphocytes may be particularly susceptible to DNA damage, suggesting a mechanism for the elevated acute leukemia risk observed among acetaminophen users.

Regular analgesic use and risk of endometrial cancer.

BACKGROUND: Analgesic use has been implicated in the chemoprevention of a number of solid tumors, but thus far, no previous research has focused on the role of aspirin in endometrial cancer etiology. METHODS: We conducted a hospital-based case-control study of 427 women with primary, incident endometrial cancer, and 427 age- and residence-matched controls without benign or malignant neoplasms. All participants received medical services at Roswell Park Cancer Institute in Buffalo, NY, and completed a comprehensive epidemiologic questionnaire. Women who reported analgesic use at least once a week for at least 6 months were classified as regular users and served as the reference group throughout the analyses. We used unconditional logistic regression analyses to compute crude and adjusted odds ratios (OR) with corresponding 95% confidence intervals (CI). RESULTS: Compared with nonusers, regular aspirin users were not at reduced risk of endometrial cancer (adjusted OR, 0.91; 95% CI, 0.66-1.26), nor were women with the highest frequency, duration, or cumulative lifetime aspirin use. When the sample was divided by body mass index status, regular aspirin use was not associated with risk among women classified as normal weight or overweight, but a significant risk reduction was seen for obese women (adjusted OR, 0.50; 95% CI, 0.27-0.92). Significant decreases in risk were also observed for obese women with the greatest frequency, duration, and cumulative aspirin use. No significant associations in the overall sample or among obese women were noted for acetaminophen use. CONCLUSION: We observed no evidence of an overall chemoprotective effect of aspirin on endometrial cancer risk, but the significant risk reductions among obese women warrant further investigation.

Associations between black tea and coffee consumption and risk of lung cancer among current and former smokers.

Although cigarette smoking is a clear risk factor for lung cancer, the other determinants of lung cancer risk among smokers are less clear. Tea and coffee contain catechins and flavonoids, which have been shown to exhibit anticarcinogenic properties. Conversely, caffeine may elevate cancer risk through a variety of mechanisms. The current study investigated the effects of regular consumption of black tea and coffee on lung cancer risk among 993 current and former smokers with primary incident lung cancer and 986 age-, sex-, and smoking-matched hospital controls with non-neoplastic conditions. Results indicated that lung cancer risk was not different for those with the highest black tea consumption (>or=2 cups/day) compared with nondrinkers of tea [adjusted odds ratio (aOR)=0.90; 95% confidence interval (CI)=0.66-1.24]. However, elevated lung cancer risk was observed for participants who consumed 2-3 cups of regular coffee daily (aOR=1.34; 95% CI=0.99-1.82) or >or=4 cups of regular coffee daily (aOR=1.51, 95% CI=1.11-2.05). In contrast, decaffeinated coffee drinking was associated with decreased lung cancer risk for both participants who consumed or=2 cups/day (aOR=0.64; 95% CI=0.51-0.80). These results suggest that any chemoprotective effects of phytochemicals in coffee and tea may be overshadowed by the elevated risk associated with caffeine in these beverages.

Fertility patterns prior to testicular cancer diagnosis.

Although prenatal factors are associated with testicular cancer etiology, few studies have examined the reproductive profiles of men prior to diagnosis. This case--control study investigated fertility patterns prior to testicular cancer diagnosis by comparing pregnancies fathered by 201 men with testicular cancer and those fathered by 204 age- and neighborhood-matched controls. Regardless of histology, men with testicular cancer were less likely to have ever fathered a live-born infant (OR 0.67, 95% CI 0.42--1.06) and had fewer offspring than control men (means 1.8 and 2.1, respectively). Cases were more likely than controls to report having an infertility diagnosis (OR 9.47, 95% CI 1.19--75.2) or a low sperm count (OR 5.85, 95% CI 1.28--26.7) prior to cancer diagnosis. No differences were observed for pregnancy loss. These results indicate that men with testicular cancer may have impaired fecundity and fertility as evidenced by an infertility diagnosis or low sperm count and fewer live births. Further research is needed to determine the extent to which reproductive factors are involved in the etiology of testicular cancer.

Regular use of aspirin or acetaminophen and risk of non-Hodgkin lymphoma.

Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of non-Hodgkin lymphoma (NHL), although previous results have been inconsistent. The current study investigated the effects of regular aspirin or acetaminophen use on non-Hodgkin lymphoma risk among 625 individuals with primary, incident NHL and 2512 age and sex matched hospital controls with non-neoplastic conditions who completed a comprehensive epidemiologic questionnaire. Results indicate that regular aspirin use may be associated with decreased NHL risk among men [adjusted odds ratio (aOR) 0.82, 95% confidence interval (CI), 0.65--1.04], but not among women (aOR 0.93, 95% CI, 0.71--1.23). In contrast, regular acetaminophen use was associated with elevated NHL risk among women (aOR 1.71, 95% CI, 1.18--2.50) but not among men (aOR 0.75, 95% CI, 0.48--1.17). Other studies have demonstrated that acetaminophen is associated with transient decreases in DNA repair, and lymphocytes may be particularly susceptible to DNA damage, suggesting a mechanism for the elevated NHL risk observed.

Environmental exposure to polychlorinated biphenyls and breast cancer risk.

Breast cancer is a major public health problem in the United States and in most industrialized countries. Although epidemiologic studies have identified a number of established risk factors for this disease, these factors explain only a small proportion of breast cancer incidence. Environmental exposure has been implicated in breast cancer etiology because of the vast geographic variation in breast cancer incidence rates across countries and regions within countries. Further, the steady increase in breast cancer rates over the past decades points to a potential role of environmental exposure in its development. One suspected environmental factor is the polychlorinated biphenyls (PCBs), which were manufactured commercially for a variety of industrial applications from the 1930s until the 1970s. PCBs have been associated with estrogenic, tumor promoting, and immunosuppressive activities, all of which are relevant in the development of breast cancer. The purpose of this review is to summarize the growing body of epidemiological evidence on the association between environmental PCB exposure and breast cancer risk. Three major types of study design have been used to investigate such a relation: clinic-based case-control studies, retrospective case-control studies, and nested case-control studies. Although findings from clinic-based case-control studies tend to point to an adverse effect of high PCB body burden on risk, the results from the more methodologically sound retrospective and nested studies do not provide strong support for a role of PCBs in breast cancer development. The association between PCB exposure and risk among racially and genetically susceptible subgroups may warrant further investigation. Methodological challenges in the design and analysis of epidemiologic studies on PCBs and breast cancer risk are discussed.