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Background: The results of several recent epidemiologic studies suggest that estrogen replacement therapy (ERT) in postmenopausal women may decrease their risk of subsequently developing colon or colorectal cancer. However, the association is not clear, as other similar studies have failed to show this inverse relationship.Purpose: The present study attempts a more definitive analysis of the relationship between fatal colon cancer and use of ERT among women in a large prospective study of adults in the United States.Methods: Women were selected for study from the 676,526 female participants in Cancer Prevention Study II (CPS-II), a prospective mortality study of about 1.2 million American men and women (from all 50 states, the District of Columbia, and Puerto Rico), begun by the American Cancer Society in 1982. The median age of the female CPS-II participants was 56 years in 1982. Vital status was determined through December 31, 1989; 630,585 participants (93.2%) were still alive and 43,862 (6.5%) had died after 7 years of follow-up. Death certificates were obtained for 96.2% of participants known to have died. At the end of follow-up, 897 colon cancer deaths were observed in a cohort of 422,373 postmenopausal women who were cancer free at study entry. Cox proportional hazards modeling was used to compute rate ratios (RRs) and to adjust for other potential risk factors. The likelihood ratio test (two-sided) was used to determine the statistical significance of the interaction terms.Results: Ever use of ERT was associated with significantly decreased risk of fatal colon cancer (RR = 0.71; 95% confidence interval [CI] = 0.61-0.83). The reduction in risk was strongest among current users (RR = 0.55; 95% CI = 0.40-0.76), and there was a significant (P = .0001) trend of decreasing risk with increasing years of use among all users: Users of 1 year or less had an RR of 0.81 (95% CI = 0.63-1.03), while users of 11 years or more had an RR of 0.54 (95% CI = 0.39-0.76). These associations were not altered in multivariate analyses controlling for other risk factors.Conclusions: In our data, estrogen therapy, particularly recent and long-term use, was associated with a substantial decrease in risk of fatal colon cancer. These results were consistent with several published studies suggesting a protective role of exogenous estrogens in the development of colorectal cancer and merit further investigation. [ABSTRACT FROM AUTHOR]

Geographic regions characterized by income inequality are associated with adverse mortality statistics, but the pathophysiologic mechanisms that mediate this ecologic relationship have not been elucidated. This study used a United States mail survey of 34158 male and 42741 female healthy-adult volunteers to test the association between residence in geographic regions with relative income inequality and the likelihood of weight gain at the waist. Respondents came from 21 states that were characterized by the household income inequality (HII) index, a measure reflecting the proportion of total income received by the more well off 50% of households in the state. The main outcome measure was self-reported weight gain mainly at the waist as opposed to weight gain at other anatomic sites. After controlling for age, other individual-level factors, and each state's median household income, men's likelihood of weight gain at the waist was positively associated (p = 0.0008) with the HII index. Men from states with a high HII (households above the median receive 81.6% to 82.6% of the income) described weight gain at the waist more often than men from states with a low HII (households above the median receive 77.0% to 78.5% of the income) (odds ratio = 1.12, 95% confidence interval 1.03 to 1.22). Women's results showed a non-significant trend in the same direction. An association between ecologically defined socio-environmental stress and abdominal obesity may help to clarify the pathophysiologic pathways leading to several major chronic diseases. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption has both adverse and beneficial effects on survival. We examined the balance of these in a large prospective study of mortality among U.S. adults.Methods: Of 490,000 men and women (mean age, 56 years; range, 30 to 104) who reported their alcohol and tobacco use in 1982, 46,000 died during nine years of follow-up. We compared cause-specific and rates of death from all causes across categories of base-line alcohol consumption, adjusting for other risk factors, and related drinking and smoking habits to the cumulative probability of dying between the ages of 35 and 69 years.Results: Causes of death associated with drinking were cirrhosis and alcoholism; cancers of the mouth, esophagus, pharynx, larynx, and liver combined; breast cancer in women; and injuries and other external causes in men. The mortality from breast cancer was 30 percent higher among women reporting at least one drink daily than among nondrinkers (relative risk, 1.3; 95 percent confidence interval, 1.1 to 1.6). The rates of death from all cardiovascular diseases were 30 to 40 percent lower among men (relative risk, 0.7; 95 percent confidence interval, 0.7 to 0.8) and women (relative risk, 0.6; 95 percent confidence interval, 0.6 to 0.7) reporting at least one drink daily than among nondrinkers, with little relation to the level of consumption. The overall death rates were lowest among men and women reporting about one drink daily. Mortality from all causes increased with heavier drinking, particularly among adults under age 60 with lower risk of cardiovascular disease. Alcohol consumption was associated with a small reduction in the overall risk of death in middle age (ages 35 to 69), whereas smoking approximately doubled this risk.Conclusions: In this middle-aged and elderly population, moderate alcohol consumption slightly reduced overall mortality. The benefit depended in part on age and background cardiovascular risk and was far smaller than the large increase in risk produced by tobacco. [ABSTRACT FROM AUTHOR]

Health effects following low doses of ionizing radiation are uncertain. Military veterans at the Nevada test site (NTS) during the SMOKY atmospheric nuclear weapons test in 1957 were reported to be at increased risk for leukemia in 1979, but this increase was not evaluated with respect to radiation dose. The SMOKY test was one of 30 tests in 1957 within the PLUMBBOB test series. These early studies led to public laws where atomic veterans could qualify for compensation for presumptive radiogenic diseases. A retrospective cohort study was conducted of 12219 veterans at the PLUMBBOB test series, including 3020 at the SMOKY nuclear test. Mortality follow-up was through 2010 and observed causes of death were compared with expected causes based on general population rates. Radiation dose to red bone marrow was based on individual dose reconstructions, and Cox proportional hazards models were used to evaluate dose response for all leukemias other than chronic lymphocytic leukemia (non-CLL leukemia). Vital status was determined for 95.3% of the 12 219 veterans. The dose to red bone marrow was low (mean 3.2 mGy, maximum 500 mGy). Military participants at the PLUMBBOB nuclear test series remained relatively healthy after 53 years and died at a lower rate than the general population. In contrast, and in comparison with national rates, the SMOKY participants showed significant increases in all causes of death, respiratory cancer, leukemia, nephritis and nephrosis, and accidents, possibly related in part to lifestyle factors common to enlisted men who made up 81% of the SMOKY cohort. Compared with national rates, a statistically significant excess of non-CLL leukemia was observed among SMOKY participants (Standardized Mortality Ratio  =  1.89, 95% 1.24-2.75, n  =  27) but not among PLUMBBOB participants after excluding SMOKY (SMR  =  0.87, 95% 0.64-1.51, n  =  47). Leukemia risk, initially reported to be significantly increased among SMOKY participants, remained elevated, but this risk diminished over time. Despite an intense dose reconstruction, the risk for leukemia was not found to increase with increasing levels of radiation dose to the red bone marrow. Based on a linear model, the estimated excess relative risk per mGy is  -0.05 (95% CI -0.14, 0.04). An explanation for the observed excess of leukemia remains unresolved but conceivably could be related to chance due to small numbers, subtle biases in the study design and/or high tobacco use among enlisted men. Larger studies should elucidate further the possible relationship between fallout radiation, leukemia and cancer among atomic veterans.

In this article, the authors focus on epidemic-assistance investigations that dealt with maternal and child health problems, including unintended and adolescent pregnancy and family planning; international reproductive health surveys among refugees; pregnancy outcomes, including abortion, maternal mortality, infant mortality, and birth defects; leukemia; and Reye syndrome. During 1946-2005, a total of 1,969 investigations had sufficient data to classify them as possibly related to maternal and child health and were characterized by distinctive periods. Those related to family planning, pregnancy intention, and reproductive health among refugees began in the early 1970s and continued through 2005. Abortion-related investigations occurred during 1971-1982. Investigations of non-abortion-related maternal morbidity and mortality began in 1979 and included 2 international epidemic-assistance investigations. Investigations of clusters of disease among infants began in the 1960s, with a special focus on Reye syndrome during 1964-1984. Investigations of childhood cancer and birth defects began in the late 1950s. The Centers for Disease Control and Prevention has used the epidemic-assistance investigations mechanism to respond to a wide range of health concerns of women and children. The investigations of abortion-related health problems might have had the best-documented impact on public policy and public health.

Previous studies of cancer incidence among persons living in municipalities within one mile of two nuclear materials processing and fabrication plants in Pennsylvania were extended for the years 1998-2004. It had been shown that mailing addresses for residents of rural areas often did not reflect the actual municipality of residence and, if not corrected, would bias study results. The previous studies had corrected for this bias. Accordingly for the extended study, we obtained mailing addresses from the Pennsylvania Department of Health (PDH) for 866 persons with cancer who presumably lived in one of eight minor civil divisions (MCDs) near or encompassing the former nuclear facilities, designated as Area 1 in previous studies conducted by the PDH. Street addresses were geocoded and local postmasters were asked to place rural delivery addresses, post office boxes and street addresses that could not be geocoded into the correct MCD of actual residence. Over 15% of the mailing addresses were found not to be within the boundaries of the Area 1 municipalities. After the mailing addresses of individuals with cancer were placed in their proper MCD of residence, the number of persons diagnosed with cancer (n = 708) and confirmed to have lived in Area 1 was as expected (728.4) based on cancer incidence rates in the general population of Pennsylvania (SIR 0.97; 95% CI 0.90-1.05). To further evaluate the patterns of cancer rates near these nuclear facilities and the influence of improved reporting and geocoding of addresses over time, analyses were conducted of publicly available cancer incidence data from 1990 through 2004. Based on mailing addresses, a steady decrease in the number of cancers reported in the Area 1 proximal MCDs was seen, in contrast to a steady rise in the number of cancers reported in seven adjacent but more distant MCDs from the nuclear facilities, designated as Area 2. These patterns were attributed to improvements over time in the geocoding of residential mailing addresses coupled with the gradual elimination and replacement of rural delivery addresses with street addresses. The incorrect placement of mailing addresses in residential Area 1 municipalities prior to about 2002 overestimated the number of cancers occurring among residents living in close proximity to the nuclear facilities and, correspondingly, underestimated the number among Area 2 residents. Summing Area 1 and Area 2 data showed that there was no change in cancer rates over time. These results are consistent with previous studies indicating that living in municipalities near the former Apollo-Parks nuclear facilities was not associated with an increase in cancer occurrence.

Information suggesting that infection may be an underlying cause of childhood leukemia and lymphoma includes the occasional appearance of cases in time-space clusters within communities and increased incidence after communities experience marked population influxes (population mixing). Among 50 clusters involving cases of childhood leukemia and lymphoma investigated in the United States in 1961-1977, eight showed suggestive evidence of underlying infectious causation. In seven of the eight communities, case occurrence was associated with the attendance of patients or their siblings at particular schools or with family participation in particular church groups. In five, rapid population growth had occurred. Other findings included the possible association of cases with unusual patterns of infectious disease (rheumatic illness in one community, chickenpox in another) and with other childhood diseases, including other forms of childhood cancer. In one community, two cases of Burkitt's lymphoma occurred at the same time, and a third case arose 3 years later in boys living in a newly developing neighborhood. Such community observations support the need for continued biologic research regarding the possible role of infectious agents in childhood leukemia and lymphoma.

An unusual county-wide excess of childhood cancers of brain and other nervous tissue in the late 1990s in St Lucie County, Florida, prompted the Florida Department of Health to conduct a case-control study within the county assessing residential chemical exposures. No clear associations were found, but claims were then made that the release of radioactive substances such as strontium 90 from the St Lucie nuclear power station, which began operating in 1976, might have played a role. To test the plausibility of this hypothesis, we extended by 17 years a previous study of county mortality conducted by the National Cancer Institute. Rates of total cancer, leukaemia and cancer of brain and other nervous tissue in children and across all ages in St Lucie County were evaluated with respect to the years before and after the nuclear power station began operation and contrasted with rates in two similar counties in Florida (Polk and Volusia). Over the prolonged period 1950-2000, no unusual patterns of childhood cancer mortality were found for St Lucie County as a whole. In particular, no unusual patterns of childhood cancer mortality were seen in relation to the start-up of the St Lucie nuclear power station in 1976. Further, there were no significant differences in mortality between the study and comparison counties for any cancer in the time period after the power station was in operation. Relative rates for all childhood cancers and for childhood leukaemia were higher before the nuclear facility began operating than after, while rates of brain and other nervous tissue cancer were slightly lower in St Lucie County than in the two comparison counties for both time periods. Although definitive conclusions cannot be drawn from descriptive studies, these data provide no support for the hypothesis that the operation of the St Lucie nuclear power station has adversely affected the cancer mortality experience of county residents.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

Background: Several studies have reported positive associations between environmental tobacco smoke (ETS) and increased risk of breast cancer. However, studies of active smoking and risk of breast cancer are equivocal and in general do not support a positive association. To try to resolve this paradox, we examined the association between breast cancer mortality and potential ETS exposure from spousal smoking in an American Cancer Society prospective study of U.S. adult women., Methods: We assessed breast cancer death rates in a cohort of 146 488 never-smoking, single-marriage women who were cancer free at enrollment in 1982. Breast cancer death rates among women whose husbands smoked were compared with those among women married to men who had never smoked. Cox proportional hazards modeling was used to control for potential risk factors other than ETS exposure., Results: After 12 years of follow-up, 669 cases of fatal breast cancer were observed in the cohort. Overall, we saw no association between exposure to ETS and death from breast cancer (rate ratio [RR] = 1.0; 95% confidence interval [CI] = 0.8-1.2). We did, however, find a small, not statistically significant increased risk of breast cancer mortality among women who were married before age 20 years to smokers (RR = 1. 2; 95% CI = 0.8-1.8)., Conclusions: In contrast to the results of previous studies, this study found no association between exposure to ETS and female breast cancer mortality. The results of our study are particularly compelling because of its prospective design as compared with most earlier studies, the relatively large number of exposed women with breast cancer deaths, and the reporting of exposure by the spouse rather than by proxy.

To determine the relation between multivitamin use and death from heart disease, cerebrovascular disease, and cancer, the authors examined a prospective cohort of 1,063,023 adult Americans in 1982-1989 and compared the mortality of users of multivitamins alone; vitamin A, C, or E alone; and multivitamin and vitamin A, C, or E in combination with that of vitamin nonusers by using multivariate Cox proportional hazard models. Multivitamin users had heart disease and cerebrovascular disease mortality risks similar to those of nonusers, whereas combination users had mortality risks that were 15% lower than those of nonusers. Multivitamin and combination use had minimal effect on cancer mortality overall, although mortality from all cancers combined was increased among male current smokers who used multivitamins alone (relative risk (RR) = 1.13, 95% confidence interval (CI): 1.05, 1.23) or in combination with vitamin A, C, or E (RR = 1.16, 95% CI: 1.06, 1.26), but decreased in male combination users who had never (RR = 0.86, 95% CI: 0.74, 0.99) or had formerly (RR = 0.90, 95% CI: 0.82, 0.98) smoked. No such associations were seen in women. These observational data provide limited support for the hypothesis that multivitamin use in combination with vitamin A, C, or E may reduce heart disease and cardiovascular disease mortality, but add to concerns raised by randomized studies that some vitamin supplements may adversely affect male smokers.

We assessed the impact of smoking cessation on subsequent death rates among a cohort of 51,343 men and 66,751 women in California enrolled in late 1959 in the original American Cancer Society (ACS) Cancer Prevention Study (CPS I) and followed for 38 years. We compared the age-adjusted death rate, expressed as deaths per 1,000 person-years, among all subjects who smoked cigarettes in 1959 but who had largely quit as of 1997 with the death rate among never smokers over a 38-year period. The all causes death rate for males decreased from 20.67 during 1960-1969 to 18.68 during 1960-1997 for smokers and decreased from 10.51 to 9.46 for never smokers. The lung cancer death rate for males increased from 1.558 to 1.728 for smokers and increased from 0.127 to 0.133 for never smokers. The all causes death rate for females increased from 9.54 to 10.14 for smokers and decreased from 6.95 to 6.44 for never smokers. The lung cancer death rate for females increased greatly from 0.208 to 0.806 for smokers and increased from 0.094 to 0.116 for never smokers. These results indicate there has been no important decline in either the absolute or relative death rates from all causes and lung cancer for cigarette smokers as a whole compared with never smokers in this large cohort, in spite of a substantial degree of smoking cessation. While cessation clearly reduces the mortality risk among long-term former smokers, the population impact of cessation appears to be less than currently believed.

Background: Age-adjusted rates of lung cancer among whites, but not blacks, in Duval County Jacksonville), Florida, have been among the highest of any metropolitan area of the United States for three decades., Methods: We conducted a case-control study, interviewing 507 patients with lung cancer diagnosed from 1993 to 1996 and 1,007 control subjects, randomly selected from the county population., Results: Cigarette smoking was the dominant cause of lung cancer (odds ratios, 59 among male current smokers; 30 among female current smokers). Both prevalence and intensity of smoking were excessive for whites but less for blacks when compared with national norms. Little association was found with residential patterns, indices of air quality, or occupation. Risk doubled with increased intake of dietary fat and with a family history of lung cancer., Conclusions: Life-style factors, especially smoking, but not environmental factors, appear responsible for the high rates of lung cancer in northeast Florida.

Background: Cigarette smoking is among the few unequivocal risk factors for the development of pancreatic ductal adenocarcinoma (PDAC). Activating mutations in codon 12 of the K-ras protooncogene is a frequent and early molecular event in the pathogenesis of PDAC and a variety of nonmalignant ductal pancreatic lesions. The molecular epidemiologic relation between heavy cigarette smoking and mutational activation of K-ras in PDAC has been examined to a limited extent. The authors have examined the mutational status of K-ras in nonneoplastic pancreata in relation to cigarette smoking status., Methods: Archival formalin fixed paraffin embedded specimens of nonneoplastic pancreata (n = 39) were obtained from the American Cancer Society and evaluated histopathologically. Specimens from age- and gender-matched individuals were stratified into three groups: 1) those who never smoked cigarettes (n = 16), 2) those who smoked 1-2 packs/day for more than 20 years (n = 10 cases), and 3) those who smoked more than 2 packs/day for 20 or more years (n = 13). Cases were preselected from 77 specimens based on the quality, suitability, and cellularity of the archival tissues for analyses. Furthermore, none of the patients died of primary PDAC or had evidence of pancreatic metastases from an extrapancreatic primary tumor. Tissue sections were microdissected and deparaffinized, and genomic DNA was purified by standard proteinase K-phenol-chloroform extraction techniques. Genomic DNA was analyzed for mutations in codon 12 of the K-ras protooncogene by two mutant-allele-enriched polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assays and by multiplex PCR-based ligase chain reaction (LCR) analyses., Results: Analyses of multiple microdissected pancreata specimens from 39 cases revealed wild-type K-ras codon 12 sequences in both nonsmoking individuals and those who smoked 1-2 packs/day for 20 or more years. K-ras codon 12 mutations were confirmed by PCR-RFLP and PCR-LCR assays in 5 of 13 pancreata cases (39%) obtained from individuals who smoked more than 2 packs of cigarettes/day for 20 years or more (P < 0.005). The K-ras mutation spectra revealed two G-->T transversions, one G-->C transversion and two G-->A transitions. There was no clear relation between the incidence or spectra of mutations and pancreatic histopathology, as overtly normal pancreata as well as pancreata with squamous metaplasia, periductal fibrosis, and ductal atypia revealed reproducible K-ras alterations. Similarly, among those 34 cases in which a wild-type K-ras sequence was revealed by both approaches, a similar histopathologic profile was evident., Conclusions: Mutational activation of codon 12 of the K-ras protooncogene was confirmed reproducibly by mutant allele-enriched PCR-RFLP and multiplex PCR-LCR analyses in 39% (5 of 13) of archival nonneoplastic pancreata from age- and gender-matched individuals who smoked more than 2 packs of cigarettes/day for 20 or more years. The presence of a mutated or wild-type or K-ras was independent of the histopathologic profile of the 39 cases examined. The data provide further suggestive molecular epidemiologic evidence of an association between a major and unequivocal risk factor for PDAC (heavy cigarette smoking) and mutations in a molecular target (K-ras), the activation of which is an important and early event both in the pathogenesis of PDAC and in the development of a variety of nonneoplastic ductal pancreatic lesions.

Objectives: It is difficult to separate the possible role of fertility drugs from underlying infertility as risk factors for ovarian cancer. The present study examined the relationship between self-reported infertility and death from ovarian cancer among married women unlikely to have been exposured to fertility drugs., Methods: Women were selected for study from the 676,526 female participants in Cancer Prevention Study II (CPS-II). After twelve years of follow-up, 797 deaths from ovarian cancer were observed among women with no prior history of cancer or hysterectomy and 40 years of age or older in 1967 when ovulatory stimulants were approved in the United States. Cox proportional hazards modeling was used to compute rate ratios (RRs) and to adjust for other potential risk factors., Results: Overall, self-reported infertility was not significantly associated with ovarian cancer mortality (adjusted rate ratio (RR) = 1.1, 95 percent confidence interval (CI) = 0.9-1.3). Ovarian cancer death rates among nulligravid women with self-reported infertility, however, were 40 percent higher than for nulligravid women who never tried to become pregnant (RR = 1.4, 95 percent CI = 0.9-2.4). Multigravid women who reported infertility problems were not at increased risk., Conclusions: These results suggest that infertility itself, without concomitant exposure to fertility drugs, may increase risk of fatal ovarian cancer among nulligravid women.

Context: Cancer registries have reported an increased incidence of melanoma and certain noncutaneous cancers following nonmelanoma skin cancer (NMSC). Whether these findings were attributable to intensified surveillance, shared risk factors, or increased cancer susceptibility remains unclear., Objective: To determine whether a history of NMSC predicts cancer mortality., Design: Prospective cohort with 12-year mortality follow-up adjusted for multiple risk factors., Setting: Cancer Prevention Study II, United States and Puerto Rico., Participants: Nearly 1.1 million adult volunteers who completed a baseline questionnaire in 1982., Main Outcome Measure: Deaths due to all cancers and common cancers., Results: After adjusting for age, race, education, smoking, obesity, alcohol use, and other conventional risk factors, a baseline history of NMSC was associated with increased total cancer mortality (men's relative risk [RR], 1.30; 95% confidence interval [CI], 1.23-1.36; women's RR, 1.26; 95% CI, 1.17-1.35). Exclusion of deaths due to melanoma reduced these RRs only slightly. Mortality was increased for the following cancers: melanoma (RR, 3.36 in men, 3.52 in women); pharynx (RR, 2.77 in men, 2.81 in women); lung (RR, 1.37 in men, 1.46 in women); non-Hodgkin lymphoma (RR, 1.32 in men, 1.50 in women); in men only, salivary glands (RR, 2.96), prostate (RR, 1.28), testis (RR, 12.7), urinary bladder (RR, 1.41), and leukemia (RR, 1.37); and in women only, breast (RR, 1.34). All-cause mortality was slightly increased (adjusted men's RR, 1.03 [95% CI, 1.00-1.06]; women's RR, 1.04 [95% CI, 1.00-1.09])., Conclusions: Persons with a history of NMSC are at increased risk of cancer mortality. Although the biological mechanisms are unknown, a history of NMSC should increase the clinician's alertness for certain noncutaneous cancers as well as melanoma.

To examine the relation between family history of breast cancer in a mother or sister and a man's risk of fatal prostate cancer, we analyzed data from a prospective mortality study of adult men in the United States. During 12 years of follow-up, there were 3,141 deaths from prostate cancer in a cohort of 480,802 men who were cancer-free at study entry in 1982. Results from Cox proportional hazards models, adjusted for other risk factors, showed a modest increased risk of fatal prostate cancer associated with a family history of breast cancer (in the absence of a family history of prostate cancer) [rate ratio (RR) = 1.16; 95% confidence interval (CI) = 1.01-1.33]. The association was stronger among men younger than 65 years of age whose relatives were diagnosed with breast cancer before age 50 years (RR = 1.65; 95% CI = 0.88-3.10) and among Jewish men (RR = 1.73; 95% CI = 1.00-2.97). The increased risks observed in these subgroups may reflect genetic alterations underlying familial clustering of prostate and breast cancer.

Objectives: Diabetes mellitus and pancreatic cancer are known to be associated, but it is not known whether diabetes is a true risk factor, preceding development of the cancer, or if it is an early manifestation of the cancer. To address this uncertainty, we examined the association of pancreatic cancer mortality and reported diabetes of at least one year's duration in a large, prospective study of United States adults. The vast majority of diabetes in this cohort is likely to be non-insulin-dependent diabetes., Methods: After 12 years of follow-up, 2,953 deaths from pancreatic cancer were observed in a cohort of 1,089,586 men and women who were cancer-free at study entry in 1982. Cox proportional hazards models, adjusted for age, race, smoking, family history of pancreatic cancer, body mass index (wt/ht2), and education, were used to assess associations., Results: A history of diabetes was significantly related to pancreatic cancer mortality in both men (rate ratio [RR] = 1.49, 95 percent confidence interval [CI] = 1.25-1.77) and women (RR = 1.51, CI = 1.24-1.85). However, the strength of the association varied over the follow-up period. The death rate from pancreatic cancer was twice as high in diabetics as in non-diabetics during the second and third years of follow-up (adjusted RR = 2.05, CI = 1.56-2.69) but only about 40 percent higher in years nine to 12 (adjusted RR = 1.38, CI = 1.08-1.77)., Conclusions: The small but persistent increased risk of death from pancreatic cancer, seen even when the diagnosis of diabetes preceded death by many years, supports the hypothesis that diabetes may be a true, albeit modest, risk factor for pancreatic cancer.

The authors examined the association between main lifetime occupation and subsequent breast cancer mortality in a large prospective study of US adults. After 9 years of follow-up, 1,780 cases of fatal breast cancer were observed among 563,395 women who were cancer-free at interview in 1982. Main lifetime occupation was derived based on self-reports of current and former occupational titles and was classified into 14 broad occupational groups and 16 more narrowly defined occupational titles. Results from Cox proportional hazards models, adjusted for breast cancer risk factors, revealed little variability in breast cancer mortality by occupation. Two significant associations were observed: In comparison with housewives, women in "administrative support, including clerical" occupations were at a small increased risk (rate ratio (RR) = 1.14, 95% confidence interval (CI) 1.01-1.31), and an increased risk was seen for "executives" (RR = 1.93, 95% CI 1.03-3.62), based on 10 breast cancer deaths. No significant increases in risk were observed for teachers and librarians (RR = 0.89), nurses (RR = 0.84), managers (RR = 0.89), or women employed in sales (RR = 0.88) or service (RR = 0.84) occupations. When analyses were limited to women who had worked in their occupation for 10 or more years, the results for each occupational title were virtually unchanged. These results offer little support for an association between occupation and breast cancer mortality in general or for particular occupational titles, including teachers and nurses.

Objective: Investigate risk factors for colon polyp using multivariate analyses., Design: In a group responding to a 1992 mail survey, we assessed the association between physician-diagnosed colon polyp and possible risk factors reported primarily 10 years earlier., Setting: Survey respondents within the Cancer Prevention Study II., Participants: Respondents, 72,868 men and 81,356 women, who reported no polyp diagnosis when questioned in 1982 at ages 40 to 64 years., Measurements and Main Results: The characteristics of 7,504 men (10.3%) and 5,111 women (6.3%) reporting a first colon polyp were compared with those of participants who did not report a polyp. After adjustments for age, family history of colorectal cancer, and other potential risk factors, polyp occurrence was associated with 1982 histories of smoking, former smoking, alcohol use of at least two drinks per day (odds ratios [ORs] from 1.5 to 1.1; all p < .005), and a body mass index > or = 28 kg/m2 (men's OR 1.06; 95% confidence interval [CI] 1.00, 1.13; women's OR 1.08; 95% CI 0.99, 1.17). Polyps were also associated with a diagnosis of gallbladder disease or gallstone at any time and with gallbladder surgery up to 1982 (OR from 2.7 to 1.3; all p < .001). Polyp occurrence was inversely associated with 1982 histories of high exercise level (men's OR 0.83; 95% CI 0.76, 0.91; women's OR 0.90; 95% CI 0.78, 1.03), frequent aspirin use in women (OR 0.85; 95% CI 0.77, 0.95), and high parity in women (OR 0.84; 95% CI 0.75, 0.94). Among participants lacking a clinically normal gallbladder, the polyp risks associated with smoking and high body mass index were reduced (p < .04 for interactions)., Conclusions: Despite the limitations and potential biases in these self-reported data, the risk factors described here may be useful for identifying persons at modestly increased risk of having a colon polyp. The effect-modifying role of gallbladder status deserves further investigation.

Although survival rates are useful for monitoring progress in the early detection and treatment of cancer and are of particular interest to patients with new diagnoses, there are limited population-based estimates of long-term survival rates. We used data collected by the Surveillance, Epidemiology, and End Results Program for cases diagnosed during 1974-1991 and followed through 1992 to estimate relative survival at 5, 10, and 15 years after diagnosis of cancer of the breast, prostate, colon and rectum, and lung. Relative survival after diagnosis of breast and prostate cancer continued to decline up through 15 years after diagnosis, whereas survival after diagnosis of lung and colon or rectal cancer remained approximately constant after 5 and 10 years, respectively. Age-specific patterns of survival varied by site, stage, and demographics. Among patients with localized breast and prostate cancer, women who were younger than age 45 at breast cancer diagnosis and men who were 75 years and older at prostate cancer diagnosis had the poorest relative survival. Relative survival among lung cancer patients decreased with age at diagnosis, regardless of stage or demographics, and age-specific patterns of relative survival for patients with cancer of the colon and rectum differed according to race. Among white patients diagnosed with cancers of the colon and rectum, relative survival did not vary by age at diagnosis; among black patients older than 45 at diagnosis, relative survival decreased with age. This study provides population-based estimates of long-term survival and confirms black/white, male/female, and stage- and age-specific differences for the major cancers.

The accuracy of self-reported cancer diagnoses in a prospective study was compared with population-based cancer registry data in four states. The study cohort included 65,582 men and women aged 39-96 years who were participants in the Cancer Prevention Study II Nutrition Survey, begun by the American Cancer Society in 1992. Estimates of sensitivity (the proportion of study participants with a registry-documented cancer who self-reported the cancer) ranged from 0.79 for an exact match of cancer site and year of diagnosis (+/- 1 year) to 0.93 for a match of any reported cancer. The sensitivity of exact matches varied considerably by cancer site and was highest for breast, prostate, and lung cancers (0.91, 0.90, and 0.90, respectively) and lowest for rectal cancer and melanoma (0.16 and 0.53, respectively). Sensitivity also varied slightly by the age, education, and smoking status of study participants. Estimates of sensitivity were virtually identical for each of the four states. The positive predictive value (the proportion of self-reported cancers that were confirmed by the registries) was 0.75 overall and also varied by cancer site. Unlike sensitivity, however, this proportion varied considerably by state. All self-reports of cancer that were not confirmed by the registries were further investigated by repeat questionnaires and acquisition of medical records. Low positive predictive values were due to underascertainment of true cancer cases by the registries, inaccurate reporting on the part of study participants, and problems with the algorithm used by the state to link the study population to the registry data. In conclusion, the ability of members of this cohort to report a past diagnosis of cancer accurately is quite high, especially for cancers of the breast, prostate, lung, and colon, or for the occurrence of any cancer.

Key findings on cancer incidence and mortality are presented for five racial and ethnic groups in the United States--African Americans, American Indians, Asians and Pacific Islanders, Hispanics, and whites. Information on the prevalence of cancer risk factors and screening examinations among these racial and ethnic groups is also included.

Background: Adenocarcinoma of the lung, once considered minimally related to cigarette smoking, has become the most common type of lung cancer in the United States. The increased incidence of this cancer might be explained by advances in diagnostic technology (i.e., increased ability to perform biopsies on tumors in smaller, more distal airways), changes in cigarette design (e.g., the adoption of filtertips), or changes in smoking practices. We examined data from the Connecticut Tumor Registry and two American Cancer Society studies to explore these possibilities., Methods: Connecticut Tumor Registry data from 1959 through 1991 were analyzed to determine whether the increase in lung adenocarcinoma observed during that period could be best described by birth cohort effects (i.e., generational changes in cigarette smoking) or calendar period effects (i.e., diagnostic advances). Associations between cigarette smoking and death from specific types of lung cancer during the first 2 years of follow-up in Cancer Prevention Study I (CPS-I), initiated in 1959) and Cancer Prevention Study II (CPS-II, initiated in 1982) were also examined., Results: Adenocarcinoma incidence in Connecticut increased nearly 17-fold in women and nearly 10-fold in men from 1959 through 1991. The increases followed a clear birth cohort pattern, paralleling gender and generational changes in smoking more than diagnostic advances. Cigarette smoking became more strongly associated with death from lung adenocarcinoma in CPS-II compared with CPS-I, with relative risks of 19.0 (95% confidence interval [CI] = 8.3-47.7) for men and 8.1 (95% CI = 4.5-14.6) for women in CPS-II and 4.6 (95% CI = 1.7-12.6) for men and 1.5 (0.3-7.7) for women in CPS-I., Conclusions: The increase in lung adenocarcinoma since the 1950s is more consistent with changes in smoking behavior and cigarette design than with diagnostic advances.

To examine the relation between fatal prostate cancer and family history of prostate cancer in a first-degree relative, we analyzed data from a prospective mortality study of 481,011 men with no history of cancer at enrollment in 1982. During 9 years of follow-up, 1,922 deaths from prostate cancer occurred. Results from Cox proportional hazard models showed that family history of prostate cancer was related to fatal prostate cancer [rate ratio (RR) = 1.60; 95% confidence interval (CI) = 1.31-1.97]; men with two or more affected relatives had a greater than threefold increase in risk (RR = 3.19; 95% CI = 1.51-6.71). Men whose relatives were diagnosed with prostate cancer before age 65 years (RR = 2.03; 95% CI = 1.33-3.09) had a greater effect of family history than men whose relatives were diagnosed at older ages (RR = 1.50; 95% CI = 1.17-1.91). Rate ratios did not increase with decreasing age of the study participants. The 60% increase in risk for men with at least one affected relative is lower than that reported in previous studies.

Objective: To identify contrasts between the risk factors associated with abdominal weight gain and those associated with peripheral weight gain., Design: Prospective mail survey., Subjects: 44080 white, non-Hispanic, healthy women who were questioned in 1982 (baseline age 40-54 y) and 1992 about weight, diet, alcohol use, smoking, 10 physical activities and other variables., Measurements: Self reports in 1992 identified 4261 women who gained weight in the abdomen and 7440 women who gained in the periphery (sites other than the abdomen). Using identical logistic models adjusted for age, baseline body mass index (BMI) and numerous covariates, the abdominal-gain group and the peripheral-gain group were separately compared with 10,888 women who did not gain weight., Results: The likelihood of abdominal gain exceeded that of peripheral gain (by comparison of estimated odds ratios, abdominal vs peripheral) for high meat eaters (1.50 vs 1.15), frequent users of liquor (1.09 vs 0.54), moderate cigarette smokers (0.86 vs 0.59), heavy cigarette smokers (0.96 vs 0.36), cigarette quitters (2.13 vs 1.63), women with high parity (1.52 vs 1.15) and those who reported major weight gain since age 18 y (1.22 vs 0.65). Abdominal gain was less likely than peripheral gain for high vegetable eaters (0.71 vs 0.91), women who exercised > or = 4 h/wk [(especially aerobics/ calisthenics (0.28 vs 0.91) or walking (0.84 vs 1.06)], women who completed menopause (0.74 vs 0.98) and consistent users of estrogen replacement therapy (0.93 vs 1.22)., Conclusion: A behavior or characteristic may be associated differently with the risks of abdominal and peripheral weight gain. This insight could strengthen recommendations for preventing major chronic diseases.

Objectives: The purpose of this study was to identify behaviors associated with change in body mass index or with weight gain at the waist., Methods: A cohort of 79236 White, non-Hispanic, healthy adults was questioned in 1982 and 1992 about diet and 10 physical activities. Estimates were made of the mean effects of stable behaviors on 10-year change in body mass index and on odds ratios for gain at the waist., Results: Ten-year changes in body mass index was associated positively with meat consumption and smoking cessation and inversely with vegetable consumption, vitamin E supplementation, continued smoking, and some vigorous activities (e.g., jogging/running). Women's body mass index decreased with walking 4 or more hours per week and with regular alcohol intake, but these behaviors had a smaller effect on men's body mass index. weight gain was inversely associated with high vegetable consumption, walking 4 or more hours per week, and jogging/running 1 to 3 hours per week but not with less demanding physical activities., Conclusions: Simple derivation of behaviors associated with weight loss or reduced abdominal obesity may enhance programs designed to prevent obesity and chronic diseases.

The authors examined the relation of hypertension, use of diuretics, and use of antihypertensive medications to the risk of fatal renal cell cancer in a prospective cohort study of 998,904 adult Americans followed for 7 years (1982-1989). Analysis included 335 renal cell cancer deaths (123 in women and 212 in men). Cox proportional hazards modeling was used to calculate rate ratios. Increased rate ratios were present for cigarette smoking in men and for elevated body mass index in both sexes. Significantly increased age-matched rate ratios, independent of smoking and body mass index, were present for hypertension, use of diuretics, and use of hypertension medications, but only for women. Multivariate testing confined these risks to hypertensive women who were using hypertension medications alone (rate ratio = 2.2, 95% confidence interval 1.4-3.5) or with diuretics (rate ratio 2.5, 95% confidence interval 1.5-4.3). Risk was not significantly increased for either men or women who had untreated hypertension or who used diuretics alone with or without hypertension. These findings partly support those of earlier studies suggesting that medications related to treatment of hypertension, or the severity of hypertension itself, may contribute to the etiology of renal cell cancer.

The authors examined the relation between smoking and the risk of fatal prostate cancer in a large prospective mortality study of 450,279 men who were cancer free at enrollment in 1982. During 9 years of follow-up, 1,748 deaths occurred from prostate cancer. Cox proportional hazards modeling was used to adjust for other risk factors. Current cigarette smoking was associated with fatal prostate cancer (rate ratio = 1.34, 95% confidence interval (CI) 1.16-1.56). The rate ratio was greater at younger ages, decreasing from 1.83 (95% CI 1.04-3.24) among men below the age of 60 years to 1.11 (95% CI 0.79-1.58) among men aged 80 years and above (p for trend = 0.16). No trend in risk was observed with the number of cigarettes per day or with the duration of smoking among current smokers at baseline, and no increased risk was found among former smokers. Race did not significantly modify the association between cigarette smoking and fatal prostate cancer. These data, together with those of three other large prospective studies that find higher death rates from prostate cancer in current cigarette smokers, and inconsistent findings in incidence studies suggest that smoking may adversely affect survival in prostate cancer patients.

Several studies suggest that tubal sterilization may decrease the risk of ovarian cancer. Data from the Cancer Prevention Study II were analyzed to examine the relation between tubal ligation and ovarian cancer mortality in a large prospective study. A total of 396,114 women who had not had hysterectomies and who had no prior history of cancer (except nonmelanoma skin cancer) were followed prospectively for approximately 9 years from 1982 to 1991. During this time, 799 ovarian cancer deaths were observed. Tubal ligation was significantly associated with a decreased risk of ovarian cancer mortality in an age- and race-adjusted Cox proportional hazards model (hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.42-0.96), and the results were essentially unchanged when controlling for potential ovarian cancer risk factors (HR = 0.68, 95% CI 0.45-1.03). The protective effect appeared to be greater in the first 20 years after the procedure (HR = 0.49, 95% CI 0.24-0.99) than later (HR = 0.80, 95% CI 0.48-1.34). No interactions between ever having had a tubal ligation and other covariates were observed. These data suggest that tubal ligation reduces the risk of fatal ovarian cancer.

Background: The molecular pathology underlying the development and progression of ductal pancreatic adenocarcinoma is poorly understood relative to that of other major cancers in industrialized societies. The frequency, nature, and distribution of p53 abnormalities, their temporal relationship to the metastatic and clinicopathologic phenotypes of sporadic and familial pancreatic cancer, and their consequent effects on the genetics and expression of critical wild-type p53-regulated genes (mdm-2 and p21/WAF-1) warrant examination in pancreatic adenocarcinoma. This molecular and immunochemical study of the p53, mdm-2, and p21/ WAF-1 genes and gene products examined the largest series of nonneoplastic, neoplastic, and metastatic ductal pancreatic lesions reported to date in relation to clinicopathologic profile., Methods: Histologically confirmed specimens of primary (n = 136) and metastatic (n = 23) sporadic and familial ductal pancreatic adenocarcinoma lesions were subjected to immunochemical analyses of p53 expression in which a panel of 3 antibodies was utilized. A panel of nonneoplastic but histologically abnormal pancreatic lesions (n = 77) from individuals with varied histories of cigarette smoking were subjected to similar immunohistochemical examinations. In addition, 3 specimens from patients with chronic pancreatitis, 2 specimens of normal fetal pancreata, and 16 specimens of normal adult pancreata were examined as control tissues. Suitable frozen and archival microdissected tumor lesions were evaluated for mutations in exons 4-9 of the p53 gene by single strand conformation polymorphism (SSCP) and dideoxy sequencing analyses in which two distinct sets of outer and nested intron-based amplification primers were used for each exon. A subset of 25 tumor specimens and 18 tumor-derived cell lines for which the p53 mutation status was known were examined for amplification and/or overexpression of the mdm-2 gene; amplification was determined by Southern hybridization and overexpression by immunohistochemical and Western blot analyses. Similarly, mutations in the coding region of p21/WAF-1 gene were examined by SSCP and DNA sequence analyses, and steady-state expression of the p21/WAF-1 protein was assessed by Western blot analysis in these subsets of tumors and tumor-derived cell lines., Results: Positive ductal nuclear p53 immunostaining was demonstrated in 56% of primary tumors and 54% of metastatic lesions. The frequency did not differ significantly between sporadic and familial lesions, and immunostaining was not observed in ductal, acinar, or islet cell elements of normal pancreata or histologically abnormal benign pancreatic lesions from cigarette smokers. A total of 70% of tumor samples revealed reproducible SSCP abnormalities for p53; 42% of these were found in exons 7 and 8. DNA sequence analysis of cases with greater than 35% epithelial cellularity (n = 25) revealed 17 missense mutations, 12 of which were transitions. Seventy-five percent of these transitions were of G:C-->A:T type. A total of 22% of the p53 mutations identified were microdeletions, along with one insertional mutation at exon 8. None of the normal pancreata from sporadic or familial lesions revealed germ-line p53 alterations. Moreover, the frequency and spectra of p53 alterations exhibited no clear, statistically significant association with tumor grade, TNM stage, or patients' cigarette-smoking histories. The mdm-2 gene was neither amplified nor overexpressed immunochemically in a subset of ductal adenocarcinomas, and there was no clear relationship between the p53 mutation status and the status of the mdm-2 gene or protein. Similarly, SSCP and DNA sequence analysis of the p21/WAF-1 gene revealed only 2 genetic abnormalities in a series of 25 primary tumors and 15 tumor-derived cell lines; 1 of the cell lines also revealed the absence of immunoreactive p21/WAF-1 protein...

Environmental tobacco smoke (ETS) has been classified as a human lung carcinogen by the United States Environmental Protection Agency (EPA), based both on the chemical similarity of sidestream and mainstream smoke and on slightly higher lung cancer risk in never-smokers whose spouses smoke compared with those married to nonsmokers. We evaluated the relation between ETS and lung cancer prospectively in the US, among 114,286 female and 19,549 male never-smokers, married to smokers, compared with about 77,000 female and 77,000 male never-smokers whose spouses did not smoke. Multivariate analyses, based on 247 lung cancer deaths, controlled for age, race, diet, and occupation. Dose-response analyses were restricted to 92,222 women whose husbands provided complete information on cigarette smoking and date of marriage. Lung cancer death rates, adjusted for other factors, were 20 percent higher among women whose husbands ever smoked during the current marriage than among those married to never-smokers (relative risk [RR] = 1.2, 95 percent confidence interval [CI] = 0.8-1.6). For never-smoking men whose wives smoked, the RR was 1.1 (CI = 0.6-1.8). Risk among women was similar or higher when the husband continued to smoke (RR = 1.2, CI = 0.8-1.8), or smoked 40 or more cigarettes per day (RR = 1.9, CI = 1.0-3.6), but did not increase with years of marriage to a smoker. Most CIs included the null. Although generally not statistically significant, these results agree with the EPA summary estimate that spousal smoking increases lung cancer risk by about 20 percent in never-smoking women. Even large prospective studies have limited statistical power to measure precisely the risk from ETS.