Food group intake and risk of subtypes of esophageal and gastric cancer.

Incidence rates for adenocarcinomas of the esophagus and gastric cardia have been increasing rapidly, while rates for non-cardia gastric adenocarcinoma and esophageal squamous cell carcinoma have declined. We examined food group intake as a risk factor for subtypes of esophageal and gastric cancers in a multicenter, population-based case-control study in Connecticut, New Jersey and western Washington state. Associations between food groups and risk were estimated using adjusted odds ratios (OR), based on increasing intake of one serving per day. Total vegetable intake was associated with decreased risk of esophageal adenocarcinoma (OR = 0.85, 95% CI = 0.75, 0.96). Conversely, total meat intake was associated with increased risk of esophageal adenocarcinoma (OR = 1.43, 95% CI = 1.11, 1.83), gastric cardia adenocarcinoma (OR = 1.37, 95% CI = 1.08, 1.73) and noncardia gastric adenocarcinoma (OR = 1.39, 95% CI = 1.12, 1.71), with red meat most strongly associated with esophageal adenocarcinoma risk (OR = 2.49, 95% CI = 1.39, 4.46). Poultry was most strongly associated with gastric cardia adenocarcinoma (OR = 1.89, 95% CI = 1.15, 3.11) and noncardia gastric adenocarcinoma (OR = 1.90, 95% CI = 1.19, 3.03). High-fat dairy was associated with increased risk of both esophageal and gastric cardia adenocarcinoma. Higher intake of meats, particularly red meats, and lower intake of vegetables were associated with an increased risk of esophageal adenocarcinoma, while higher intake of meats, particularly poultry, and high-fat dairy was associated with increased risk of gastric cardia adenocarcinoma.

A combined analysis of North American case-control studies of residential radon and lung cancer.

Cohort studies have consistently shown underground miners exposed to high levels of radon to be at excess risk of lung cancer, and extrapolations based on those results indicate that residential radon may be responsible for nearly 10-15% of all lung cancer deaths per year in the United States. However, case-control studies of residential radon and lung cancer have provided ambiguous evidence of radon lung cancer risks. Regardless, alpha-particle emissions from the short-lived radioactive radon decay products can damage cellular DNA. The possibility that a demonstrated lung carcinogen may be present in large numbers of homes raises a serious public health concern. Thus, a systematic analysis of pooled data from all North American residential radon studies was undertaken to provide a more direct characterization of the public health risk posed by prolonged radon exposure. To evaluate the risk associated with prolonged residential radon exposure, a combined analysis of the primary data from seven large scale case-control studies of residential radon and lung cancer risk was conducted. The combined data set included a total of 4081 cases and 5281 controls, representing the largest aggregation of data on residential radon and lung cancer conducted to date. Residential radon concentrations were determined primarily by a-track detectors placed in the living areas of homes of the study subjects in order to obtain an integrated 1-yr average radon concentration in indoor air. Conditional likelihood regression was used to estimate the excess risk of lung cancer due to residential radon exposure, with adjustment for attained age, sex, study, smoking factors, residential mobility, and completeness of radon measurements. Although the main analyses were based on the combined data set as a whole, we also considered subsets of the data considered to have more accurate radon dosimetry. This included a subset of the data involving 3662 cases and 4966 controls with a-track radon measurements within the exposure time window (ETW) 5-30 yr prior to the index date considered previously by Krewski et al. (2005). Additional restrictions focused on subjects for which a greater proportion of the ETW was covered by measured rather than imputed radon concentrations, and on subjects who occupied at most two residences. The estimated odds ratio (OR) of lung cancer generally increased with radon concentration. The OR trend was consistent with linearity (p = .10), and the excess OR (EOR) was 0.10 per Bq/m3 with 95% confidence limits (-0.01, 0.26). For the subset of the data considered previously by Krewski et al. (2005), the EOR was 0.11 (0.00, 0.28). Further limiting subjects based on our criteria (residential stability and completeness of radon monitoring) expected to improve radon dosimetry led to increased estimates of the EOR. For example, for subjects who had resided in only one or two houses in the 5-30 ETW and who had a-track radon measurements for at least 20 yr of this 25-yr period, the EOR was 0.18 (0.02, 0.43) per 100 Bq/m3. Both estimates are compatible with the EOR of 0.12 (0.02, 0.25) per 100 Bq/m3 predicted by downward extrapolation of the miner data. Collectively, these results provide direct evidence of an association between residential radon and lung cancer risk, a finding predicted by extrapolation of results from occupational studies of radon-exposed underground miners.

An overview of the North American residential radon and lung cancer case-control studies.

Lung cancer has held the distinction as the most common cancer type worldwide since 1985 (Parkin et al., 1993). Recent estimates suggest that lung cancer accounted for 1.2 million deaths worldwide in 2002, which represents 17.6% of the global cancer deaths (Parkin et al., 2005). During 2002, the highest lung cancer rates for men worldwide reportedly occurred in North America and Eastern Europe, whereas the highest rates in females occurred in North America and Northern Europe (Parkin et al., 2005). While tobacco smoking is the leading risk factor for lung cancer, because of the magnitude of lung cancer mortality, even secondary causes of lung cancer present a major public health concern (Field, 2001). Extrapolations from epidemiologic studies of radon-exposed miners project that approximately 18,600 lung cancer deaths per year (range 3000 to 41,000) in the United States alone are attributable to residential radon progeny exposure (National Research Council, 1999). Because of differences between the mines and the home environment, as well as differences (such as breathing rates) between miners and the general public, there was a need to directly evaluate effects of radon in homes. Seven major residential case-control radon studies have been conducted in North America to directly examine the association between prolonged radon progeny (radon) exposure and lung cancer. Six of the studies were performed in the United States including studies in New Jersey, Missouri (two studies), Iowa, and the combined states study (Connecticut, Utah, and southern Idaho). The seventh study was performed in Winnipeg, Manitoba, Canada. The residential case-control studies performed in the United States were previously reviewed elsewhere (Field, 2001). The goal of this review is to provide additional details regarding the methodologies and findings for the individual studies. Radon concentration units presented in this review adhere to the types (pCi/L or Bq/m3) presented in the individual studies. One picocurie per liter is equivalent to 37 Bq/m3. Because the Iowa study calculated actual measures of exposure (concentration x time), its exposures estimates are presented in the form WLM(5-19) (Field et al., 2000a). WLM(5-19) represents the working level months for exposures that occurred 5-19 yr prior to diagnosis for cases or time of interview for control. Eleven WLM(5-19) is approximately equivalent to an average residential radon exposure of 4 pCi/L for 15 yr, assuming a 70% home occupancy.

Oral contraceptive use and cyclin D1 overexpression in breast cancer among young women.

Cyclin D1, an important cell cycle regulator, is overexpressed in several human cancers including breast. Both estrogens and progestins activate the transcription of the gene; antiestrogens have been shown to reduce cyclin D1 protein levels. Cyclin D1 protein overexpression has been strongly associated with well-differentiated, estrogen receptor-positive tumors. Little is known, however, as to whether epidemiological risk factors are related to this molecularly defined subset of tumors. Using a population-based study of young women <45 years in New Jersey, we analyzed whether oral contraceptives (OCs) and other risk factors were associated with the overexpression of cyclin D1 in breast cancer tissue. We measured cyclin D1 status in paraffin-embedded, archived tissue from 78.8% of the breast cancer cases using immunohistochemistry. Cyclin D1 was overexpressed in 33.7% of the cases (123 of 365). We used unordered polytomous logistic regression to estimate the odds ratios (ORs) for two case groups--(a) breast cancer with cyclin D1 overexpression (n = 123) and (b) breast cancer without overexpression (n = 242)--compared with 462 population-based controls. The multivariate-adjusted OR for ever use of OCs was 1.6 [95% confidence interval (CI), 1.0-2.5] for cases that overexpressed cyclin D1 and 1.0 (95% CI, 0.7-1.5) for those with no overexpression. Among women who started using OCs at least 20 years before the reference date, the OR was increased 2-fold for breast cancer with cyclin D1 overexpression (OR, 2.2; 95% CI, 1.2-4.0) but not for breast cancer without cyclin D1 overexpression (OR, 1.1; 95% CI, 0.7-1.8). If replicated, these findings suggest that early OC use may be associated with the subset of mammary tumors that overexpress cyclin D1.

Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study.

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.

Occupation, pesticide exposure and risk of multiple myeloma.

OBJECTIVES: This population-based case-control study examined the relationship between occupation, living or working on a farm, pesticide exposure, and the risk of multiple myeloma. METHODS: The study included 573 persons newly diagnosed with myeloma and 2131 controls. Information was obtained on sociodemographic factors, occupational history, and history of living and working on a farm. Occupational and industrial titles were coded by standardized classification systems. A job-exposure matrix was developed for occupational pesticide exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. RESULTS: Farmers and farm workers had odds ratios of 1.9 (95% CI 0.8-4.6) and 1.4 (95% CI 0.8-2.3), respectively. An odds ratio of 1.7 (95% CI 1.0-2.7) was observed for sheep farm residents or workers, whereas no increased risks were found for cattle, beef, pig, or chicken farm residents or workers. A modestly increased risk was observed for pesticides (OR 1.3, 95% CI 0.9-1.8). Significantly increased risks were found for pharmacists, dieticians and therapists (OR 6.1, 95% CI 1.7-22.5), service occupations (OR 1.3, 95% CI 1.02-1.7), roofers (OR 3.3, 95% CI 1.1-9.8), precision printing occupations (OR 10.1, 95% CI 1.03-99.8), heating equipment operators (OR 4.7, 95% CI 1.4-15.8), and hand molders and casters (OR 3.0, 95% CI 1.0-8.4). CONCLUSIONS: A modest increased risk of multiple myeloma is suggested for occupational pesticide exposure. The increased risk for sheep farm residents or workers indicates that certain animal viruses may be involved in myeloma risk.

Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas.

OBJECTIVES: Alcohol increases esophageal squamous carcinoma risk but has been less consistently associated with esophageal adenocarcinoma. Alcohol dehydrogenase catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a carcinogen. The alcohol dehydrogenase gene has several polymorphisms which may lead to faster conversion of ethanol to acetaldehyde, which may increase cancer risk. METHODS: We undertook a study to examine whether a common polymorphism in the alcohol dehydrogenase 3 gene was associated with a higher risk of esophageal adenocarcinoma using data and biological samples collected for the Esophageal and Gastric Cancer Study (n = 114 esophageal and gastric cardia adenocarcinoma, n = 60 non-cardia gastric carcinoma, n = 23 cases of esophageal squamous cell carcinoma and 160 controls). RESULTS: Individuals homozygous for ADH ( 3 ) (1-1) had a higher risk of each tumor type compared to individuals who had ADH ( 3 ) (2-2) or ADH ( 3 ) (1-2) genotype (OR = 1.7, 95% CI = 1.0-2.9 for esophageal and gastric cardia adenocarcinomas; OR = 1.7, 95% CI = 0.7-4.3 for esophageal squamous cell carcinoma; and OR = 2.8, 95% CI = 1.5-5.1 for non-cardia gastric cancer). The elevation in risk from homozygosity of the ADH ( 3 ) (1) allele was seen in drinkers and nondrinkers, although the risk estimate was only significant for drinkers, particularly of liquor. CONCLUSION: These data suggest ADH3 genotype may be associated with risk of esophageal and gastric cardia adenocarcinomas.

A functional polymorphism of toll-like receptor 4 gene increases risk of gastric carcinoma and its precursors.

BACKGROUND AND AIMS: TLR4 is a cell-surface signaling receptor involved in the recognition and host response to Helicobacter pylori. The TLR4+896A>G polymorphism linked with impaired reactivity to bacterial lipopolysaccharide may play a role in gastric carcinogenesis. METHODS: We assessed associations with premalignant gastric changes in 149 relatives of gastric cancer patients, including 45 with hypochlorhydria and gastric atrophy. We also genotyped 2 independent Caucasian population-based case-control studies of upper gastrointestinal tract cancer, initially in 312 noncardia gastric carcinoma cases and 419 controls and then in 184 noncardia gastric carcinomas, 123 cardia carcinomas, 159 esophageal cancers, and 211 frequency-matched controls. Odds ratios were computed from logistic models and adjusted for potential confounding factors. RESULTS: TLR4+896G carriers had an 11-fold (95% confidence interval [CI], 2.5-48) increased odds ratio (OR) for hypochlorhydria; the polymorphism was unassociated with gastric acid output in the absence of H pylori infection. Carriers also had significantly more severe gastric atrophy and inflammation. Seventeen percent of gastric carcinoma patients in the initial study and 15% of the noncardia gastric carcinoma patients in the replication study had 1 or 2 TLR4 variant alleles vs 8% of both control populations (combined OR = 2.3; 95% CI = 1.6-3.4). In contrast, prevalence of TLR4+896G was not significantly increased in esophageal squamous cell (2%, OR = 0.2) or adenocarcinoma (9%, OR = 1.4) or gastric cardia carcinoma (11%, OR = 1.4). CONCLUSIONS: Our data suggest that the TLR4+896A>G polymorphism is a risk factor for noncardia gastric carcinoma and its precursors. The findings underscore the role of the host innate immune response in outcome of H pylori infection.

Cigarette smoking and cancer risk: modeling total exposure and intensity.

A recent analysis showed that the excess odds ratio (EOR) for lung cancer due to smoking can be modeled by a function which is linear in total pack-years and exponential in the logarithm of smoking intensity and its square. Below 15-20 cigarettes per day, the EOR/pack-year increased with intensity (direct exposure rate or enhanced potency effect), suggesting greater risk for a total exposure delivered at higher intensity (for a shorter duration) than for an equivalent exposure delivered at lower intensity. Above 20 cigarettes per day, the EOR/pack-year decreased with increasing intensity (inverse exposure rate or reduced potency effect), suggesting greater risk for a total exposure delivered at lower intensity (for a longer duration) than for an equivalent exposure delivered at higher intensity. The authors applied this model to data from 10 case-control studies of cancer, including cancers of the lung, bladder, oral cavity, pancreas, and esophagus. At lower intensities, there was enhanced potency for several cancer sites, but narrow ranges for pack-years increased uncertainty, precluding definitive conclusions. At higher intensities, there was a consistent reduced potency effect across studies. The intensity effects were statistically homogeneous, indicating that after accounting for risk from total pack-years, intensity patterns were comparable across the diverse cancer sites.

Carbonated soft drink consumption and risk of esophageal adenocarcinoma.

Carbonated soft drinks (CSDs) have been associated with gastroesophageal reflux, an established risk factor for esophageal adenocarcinoma. As both CSD consumption and esophageal adenocarcinoma incidence have sharply increased in recent decades, we examined CSD as a risk factor for esophageal and gastric cancers in a U.S. multicenter, population-based case-control study. Associations between CSD intake and risk were estimated by adjusted odds ratios (ORs), comparing the highest versus lowest quartiles of intake. All statistical tests were two-sided. Contrary to the proposed hypothesis, CSD consumption was inversely associated with esophageal adenocarcinoma risk (highest versus lowest quartiles, OR = 0.47, 95% confidence interval = 0.29 to 0.76; Ptrend = .005), due primarily to intake of diet CSD. High CSD consumption did not increase risk of any esophageal or gastric cancer subtype in men or women or when analyses were restricted to nonproxy interviews. These findings indicate that CSD consumption (especially diet CSD) is inversely associated with risk of esophageal adenocarcinoma, and thus it is not likely to have contributed to the rising incidence rates.

Residential radon and risk of lung cancer: a combined analysis of 7 North American case-control studies.

BACKGROUND: Underground miners exposed to high levels of radon have an excess risk of lung cancer. Residential exposure to radon is at much lower levels, and the risk of lung cancer with residential exposure is less clear. We conducted a systematic analysis of pooled data from all North American residential radon studies. METHODS: The pooling project included original data from 7 North American case-control studies, all of which used long-term alpha-track detectors to assess residential radon concentrations. A total of 3662 cases and 4966 controls were retained for the analysis. We used conditional likelihood regression to estimate the excess risk of lung cancer. RESULTS: Odds ratios (ORs) for lung cancer increased with residential radon concentration. The estimated OR after exposure to radon at a concentration of 100 Bq/m3 in the exposure time window 5 to 30 years before the index date was 1.11 (95% confidence interval = 1.00-1.28). This estimate is compatible with the estimate of 1.12 (1.02-1.25) predicted by downward extrapolation of the miner data. There was no evidence of heterogeneity of radon effects across studies. There was no apparent heterogeneity in the association by sex, educational level, type of respondent (proxy or self), or cigarette smoking, although there was some evidence of a decreasing radon-associated lung cancer risk with age. Analyses restricted to subsets of the data with presumed more accurate radon dosimetry resulted in increased estimates of risk. CONCLUSIONS: These results provide direct evidence of an association between residential radon and lung cancer risk, a finding predicted using miner data and consistent with results from animal and in vitro studies.

Demographic and lifestyle predictors of survival in patients with esophageal or gastric cancers.

BACKGROUND AND AIMS: Risk factors for subtypes of esophageal and gastric cancer recently have been identified, but their effect on survival is unknown. METHODS: Incident cases (n = 1142) from a population-based case-control study were followed-up from diagnosis (1993-1995) until 2000. Cox regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for esophageal and gastric cancer in relation to prediagnostic factors. RESULTS: Relative to distant stage, esophageal adenocarcinoma (EA) patients with localized disease had a decreased risk for death (HR, .22; 95% CI, .15-.31), followed by those with regional spread (HR, .32; 95% CI, .23-.45). Similar patterns were seen for the other tumor types. Except for other (non-cardia) gastric adenocarcinomas (OGA), higher household income (> or =15,000 US dollars/y vs. <15,000 US dollars/y) was associated with a 33%-38% decrease in risk for death. Prediagnosis body mass index (BMI) between 25 and 29.9 kg/m 2 was associated with longer survival for EA and OGA patients (EA: HR, .67; 95% CI, .51-.88) vs. BMI <25 kg/m(2). Women with esophageal squamous cell carcinoma (ES) and OGA experienced longer survival compared with men. Age, education, cigarette smoking, alcohol intake, gastroesophageal reflux disease, and nonsteroidal anti-inflammatory drug use did not consistently predict survival. CONCLUSIONS: Predictors of lengthened esophageal and gastric cancer survival included higher income (except in OGA), overweight (among EA and OGA patients), and female sex (among ES and OGA patients).

Breast cancers among very young premenopausal women (United States).

OBJECTIVE: To assess risk factors for breast cancer among very young compared to older premenopausal women. METHODS: Between 1990 and 1992 a population-based case-control study conducted in Atlanta, GA, Seattle/Puget Sound, WA, and central NJ interviewed 3307 premenopausal women aged 20-54 years. Logistic regression models estimated adjusted relative risks (RR) and 95% confidence intervals (CI) for each of three 10-year age groups. RESULTS: Among the youngest age group (<35 years, n = 545), significant predictors of risk included African-American race (RR = 2.66: 95% CI 1.4-4.9) and recent use of oral contraceptives (RR = 2.26; 95% CI 1.4-3.6). Although these relationships were strongest for estrogen receptor-negative (ER-) tumors (RRs of 3.30 for race and 3.56 for recent oral contraceptive use), these associations were also apparent for young women with ER+ tumors. Delayed childbearing was a risk factor for ER+ tumors among the older premenopausal women (Ptrend < 0.01), but not for women <35 years in whom early childbearing was associated with an increased risk, reflecting a short-term increase in risk immediately following a birth. Family history of early-onset breast cancer was more strongly associated with risk among women <35 years (RR = 3.22) than those 45-54 years (RR = 1.51). Risk factors for premenopausal breast cancer not significantly modified by age at diagnosis included early age at menarche, low body mass index, and heavy alcohol consumption. CONCLUSION: These findings suggest the possibility that women who develop breast cancers at very young ages may be etiologically as well as clinically distinct.

Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms.

BACKGROUND & AIMS: Genetic variations in proinflammatory and anti-inflammatory cytokine genes influence individual response to carcinogenic exposures. Polymorphisms in interleukin (IL)-1 beta and its endogenous receptor antagonist are associated with risk of Helicobacter pylori-related gastric cancer. The aim of this study was to evaluate the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers defined by anatomic subsite. METHODS: We assessed polymorphisms of the IL-1 gene cluster and 4 other cytokine genes in a population-based case-control study of upper gastrointestinal cancers, including gastric cardia (n = 126) and noncardia adenocarcinoma (n = 188), esophageal squamous cell carcinoma (n = 53), and adenocarcinoma (n = 108), and frequency-matched controls (n = 212). ORs for the different cancers were computed from logistic regression models adjusted for potential confounding factors. RESULTS: Proinflammatory genotypes of tumor necrosis factor alpha and IL-10 were each associated with more than doubling of the risk of noncardia gastric cancer. Carriage of multiple proinflammatory polymorphisms of IL-1B(o) IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6-5.1) for one, 5.4 (2.7-10.6) for 2, and 27.3 (7.4-99.8) for 3 or 4 high-risk genotypes. In contrast, these polymorphisms were not consistently related to the risks of esophageal or gastric cardia cancers. Polymorphisms in IL-4 and IL-6 were not associated with any of the cancers studied. CONCLUSIONS: A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.

Occupation and breast cancer in women 20-44 years of age (United States).

OBJECTIVE: To examine the relation between breast cancer risk and job history among women 20-44 years of age who participated in a multi-center, population-based, case-control study. METHODS: Participants consisted of women newly diagnosed with breast cancer (1642) and controls identified by random-digit dialing (1494). Details about the three longest jobs were collected and coded by an industrial hygienist. Odds ratios and 95% confidence intervals were calculated and adjusted for age, study site, and other breast cancer risk factors. RESULTS: Several occupational and industrial categories were found to influence breast cancer risk. Stratification of the study population by parity revealed differences in breast cancer risk between the two groups for several occupational categories, including teachers, librarians or counselors (increased risk only among parous women) and natural scientists and mathematicians (decreased risk only among nulliparous women). CONCLUSIONS: This is among the first population-based case-control studies to examine occupational history and breast cancer risk in young women, with the ability to consider a wide array of potential confounders, including reproductive characteristics. This study provides further evidence of an increased breast cancer risk for several occupations and industries. Other findings were not as strongly supported by previous investigations.

Risk of breast cancer classified by joint estrogen receptor and progesterone receptor status among women 20-44 years of age.

To gain insight into whether breast cancer tumors jointly classified by estrogen receptor (ER) and progesterone receptor (PR) status represent diseases with differing etiologies, data from a population-based case-control study of US women 20-44 years of age were analyzed. Cases included 1,556 women diagnosed between 1990 and 1992. Age- and geographic-frequency-matched controls included 1,397 women identified by random digit dialing. Heterogeneity between ER+PR+ and ER-PR- tumors was most pronounced in relation to age, race, and recreational exercise at 12-13 years of age. Multivariate-adjusted odds ratios for ER+PR+ tumors were 0.64 (95% confidence interval (CI): 0.47, 0.89) for 30-34 versus 40-44 years of age, 0.89 (95% CI: 0.63, 1.25) for Black versus White race, and 0.84 (95% CI: 0.68, 1.03) for exercise at 12-13 years of age above versus at or below the median. Corresponding odds ratios for ER-PR- tumors were 1.24 (95% CI: 0.86, 1.77), 1.51 (95% CI: 1.07, 2.14), and 1.15 (95% CI: 0.90, 1.48). Risk of ER-PR- cancer in relation to menstrual and reproductive (parity and lactation) characteristics, alcohol consumption, and family history of breast cancer was similar to that observed for ER+PR+ tumors. These findings only modestly support the hypothesis that hormonally related risk factors have differing relations with ER+PR+ versus ER-PR- tumors among younger women.

Serum selenium and risk of prostate cancer in U.S. blacks and whites.

Prostate cancer is the fourth most common cancer in men worldwide and the most common cancer in men in the United States, with reported incidence rates for U.S. blacks being the highest in the world. The etiology of prostate cancer and an explanation for the racial disparity in incidence in the United States remain elusive. Epidemiologic studies suggest that selenium, an essential trace element, may protect against the disease. To further explore this hypothesis, we measured serum selenium in 212 cases and 233 controls participating in a multicenter, population-based case-control study that included comparable numbers of U.S. black and white men aged 40-79 years. Serum selenium was inversely associated with risk of prostate cancer (comparing highest to lowest quartiles, OR = 0.71, 95% CI 0.39-1.28; p for trend = 0.11), with similar patterns seen in both blacks and whites. Cubic regression spline analysis of continuous serum selenium indicated a reduced risk of prostate cancer above concentrations of 0.135 microg/ml (median among controls) compared to a reference value set at the median of the lowest selenium quartile. Because both the selenoenzyme GPX and vitamin E can function as antioxidants, we also explored their joint effect. Consistent with other studies, the inverse association with selenium was strongest among men with low serum alpha-tocopherol concentrations. In conclusion, our results suggest a moderately reduced risk of prostate cancer at higher serum selenium concentrations, a finding that can now be extended to include U.S. blacks. Since selenium exposure varies widely throughout the world, further research on optimal concentrations for cancer prevention is justified.

Population attributable risks of esophageal and gastric cancers.

BACKGROUND: Several risk factors have been identified for esophageal adenocarcinoma, gastric cardia adenocarcinoma, esophageal squamous cell carcinoma, and noncardia gastric adenocarcinoma, but no study has comprehensively examined their contributions to the cancer burden in the general population. Herein, we estimate the population attributable risks (PARs) for various risk factors observed in a multicenter population-based case-control study. METHODS: We calculated PARs by using 293 patients with esophageal adenocarcinoma, 261 with gastric cardia adenocarcinoma, 221 with esophageal squamous cell carcinoma, 368 with noncardia gastric adenocarcinoma, and 695 control subjects. We included smoking for all four tumor types and Helicobacter pylori infection for noncardia gastric adenocarcinoma as established causal risk factors as well as several other factors for which causality is under evaluation. RESULTS: Ever smoking, body mass index above the lowest quartile, history of gastroesophageal reflux, and low fruit and vegetable consumption accounted for 39.7% (95% confidence interval [CI] = 25.6% to 55.8%), 41.1% (95% CI = 23.8% to 60.9%), 29.7% (95% CI = 19.5% to 42.3%), and 15.3% (95% CI = 5.8% to 34.6%) of esophageal adenocarcinomas, respectively, with a combined PAR of 78.7% (95% CI = 66.5% to 87.3%). Ever smoking and body mass index above the lowest quartile were responsible for 45.2% (95% CI = 31.3% to 59.9%) and 19.2% (95% CI = 4.9% to 52.0%) of gastric cardia adenocarcinomas, respectively, with a combined PAR of 56.2% (95% CI = 38.1% to 72.8%). Ever smoking, alcohol consumption, and low fruit and vegetable consumption accounted for 56.9% (95% CI = 36.6% to 75.1%), 72.4% (95% CI = 53.3% to 85.8%), and 28.7% (95% CI = 11.1% to 56.5%) of esophageal squamous cell carcinomas, respectively, with a combined PAR of 89.4% (95% CI = 79.1% to 95.0%). Ever smoking, history of gastric ulcers, nitrite intake above the lowest quartile, and H. pylori infection were responsible for 18.3% (95% CI = 6.5% to 41.8%), 9.7% (95% CI = 5.4% to 16.8%), 40.7% (95% CI = 23.4% to 60.7%), and 10.4% (95% CI = 0.3% to 79.6%) of noncardia gastric adenocarcinomas, respectively, with a combined PAR of 59.0% (95% CI = 16.2% to 91.4%). CONCLUSION: In this population, a few known risk factors account for a majority of esophageal and gastric cancers. These results suggest that the incidence of these cancers may be decreased by reducing the prevalence of smoking, gastroesophageal reflux, and being overweight and by increasing the consumption of fruits and vegetables.

Occupation and risk of esophageal and gastric cardia adenocarcinoma.

BACKGROUND: Adenocarcinomas of the esophagus and gastric cardia have risen dramatically in incidence over the past few decades, however, little research has been conducted on the occupational risk factors for these cancers. METHODS: In this population-based case-control study, lifetime job histories were compared between cases of esophageal adenocarcinoma (n = 283), gastric cardia adenocarcinoma (n = 259), and population controls (n = 689). Odds ratios (OR) and 95% confidence intervals (CI) for ever employment and by duration in various occupational and industrial categories were calculated using unconditional logistic regression. RESULTS: The risk of esophageal adenocarcinoma was elevated for persons ever employed in administrative support (OR = 1.5; 95%CI = 1.0-2.1); financial, insurance, and real estate (OR = 1.6; 95%CI = 1.0-2.4); and health services (OR = 2.2; 95%CI = 1.2-3.9). The risk of gastric cardia adenocarcinoma was increased among transportation workers (OR = 1.7; 95%CI = 1.1-2.6), as well as among carpenters (OR = 1.8; 95%CI = 0.9-3.9) and workers in the furniture manufacturing industry (OR = 2.4; 95%CI = 0.9-6.3). However, we observed few duration-response relations between length of employment in any category and cancer risk. CONCLUSIONS: This study revealed associations of esophageal adenocarcinoma with employment in administrative support, health services, and a category of financial, insurance, and real estate industries, and of gastric cardia adenocarcinoma with transportation and certain woodworking occupations. Some of these findings may be due to the play of chance associated with the multiple comparisons made in this study. Our results suggest that, overall, workplace exposures play a minor role in the etiology and upward trend of esophageal and gastric cardia adenocarcinomas.