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Epidemiologic studies investigating the relation between individual carotenoids and risk of prostate cancer have produced inconsistent results. To further explore these associations and to search for reasons prostate cancer incidence is over 50% higher in US Blacks than Whites, the authors analyzed the serum levels of individual carotenoids in 209 cases and 228 controls in a US multicenter, population-based case-control study (1986–1989) that included comparable numbers of Black men and White men aged 40–79 years. Lycopene was inversely associated with prostate cancer risk (comparing highest with lowest quartiles, odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.36, 1.15; test for trend, p = 0.09), particularly for aggressive disease (comparing extreme quartiles, OR = 0.37, 95% CI: 0.15, 0.94; test for trend, p = 0.04). Other carotenoids were positively associated with risk. For all carotenoids, patterns were similar for Blacks and Whites. However, in both the controls and the Third National Health and Nutrition Examination Survey, serum lycopene concentrations were significantly lower in Blacks than in Whites, raising the possibility that differences in lycopene exposure may contribute to the racial disparity in incidence. In conclusion, the results, though not statistically significant, suggest that serum lycopene is inversely related to prostate cancer risk in US Blacks and Whites. [ABSTRACT FROM PUBLISHER]

Objectives: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES.Methods: A cohort comprising 3,899 DES-exposed and 1,374 unexposed daughters was followed for 13 years (1982 1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates.Results: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis.Conclusions: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out. [ABSTRACT FROM AUTHOR]

Squamous cell skin cancer, though common, remains largely unreported and unstudied, with little known about its incidence and time trends. We have used a unique resource--a continuous population-based registry of cases of squamous cell skin cancer within a single prepaid health plan-to describe basic epidemiologic features of this malignancy and compare it with the more widely studied melanoma. Both malignancies are considerably more common in this population than we expected based on previous reports from the general population. From the 1960s to the 1980s, the incidence of squamous cell skin cancer increased 2.6 times in men and 3.1 times in women, while incidence of melanoma rose 3.5-fold and 4.6-fold in men and women, respectively. Skin cancers of both types involving the head and neck or the extremities increased essentially in parallel over these 27 years. Melanomas of the trunk, however, appeared to increase at a faster rate in both sexes. These observations are consistent with the impression that the rising incidence of both malignancies may be attributable to increased voluntary exposure to the sun over an extended period. [ABSTRACT FROM AUTHOR]

Objectives: Endogenous sex hormones are thought to be involved in breast and endometrial cancers, but few studies have evaluated the relationships between hormones and risk factors for these diseases.Methods: We related serum hormone and sex-hormone binding globulin (SHBG) levels to reproductive and lifestyle risk factors in a cross-sectional study of 125 postmenopausal women in five geographic regions of the United States.Results: The estrogens were associated positively, while SHBG was associated negatively with body mass index (wt/ht2). Estrone, (E1), estrone sulfate, and bioavailable estradiol (BioE2) were inversely associated with height. Androstenedione was positively associated with age at menopause, while androstenedione, E1, estradiol, and BioE2 were inversely associated with age at menarche. Weekly alcohol drinkers had higher hormone levels, and lower SHBG levels than those who abstained. Androstenedione and E1 decreased with increasing levels of nonrecreational activity.Conclusions: Several of these findings support the hypothesis that breast and endometrial cancer risk factors are mediated, in part, through increased endogenous hormone levels. The androstenedione findings are of interest in light of studies relating androstenedione to endometrial and possibly breast cancer. An association of age at menarche with E2, independent of androstenedione, may reflect increased aromatase activity in women with earlier menarche. [ABSTRACT FROM AUTHOR]

Recent discussions on research priorities in the United States have revealed a widespread assumption that known risk factors entirely explain the historic international differences in rates of breast cancer. In fact, formal investigations of this question, both by modelling between-country differences and studies of migrants, indicate that an appreciable amount of the international differences in this disease remains unexplained. If this is not recognised, opportunities for research on breast cancer aetiology may be lost. [ABSTRACT FROM AUTHOR]

Public health policy decisions in the United States have resulted in 62.4% of the population having access to fluoridated water. The purpose of this study was to examine the association between community water fluoridation and osteosarcoma. A secondary data analysis was performed with data collected from 2 separate but linked studies. Patients for phase 1 and phase 2 were selected from US hospitals via a matched case-control study design. For both phases, cases included patients diagnosed with osteosarcoma, and controls were patients diagnosed with other bone tumors or nonneoplastic conditions. In phase 1, cases ( n = 209) and controls ( n = 440) were patients of record in the participating orthopedic departments from 1989 to 1993. In phase 2, cases ( n = 108) and controls ( n = 296) were incident patients who were identified and treated by orthopedic physicians from 1994 to 2000. This analysis included all patients who met eligibility criteria on whom we had complete data on covariates, exposures, and outcome. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the association of community water fluoridation with osteosarcoma. A modestly significant interaction existed between fluoridation living status and bottled water use ( P = 0.047). The adjusted OR for osteosarcoma and ever having lived in a fluoridated area for nonbottled water drinkers was 0.51 (95% CI, 0.31 to 0.84; P = 0.008). In the same comparison, the adjusted OR for bottled water drinkers was 1.86 (95% CI, 0.54 to 6.41; P = 0.326). Findings from this study demonstrated that community water fluoridation is not associated with an increased risk for osteosarcoma.

Prenatal exposure to diethylstilbestrol (DES) is associated with adverse health outcomes, including anatomic anomalies of the reproductive tract in women and of the genitourinary tract in men. The mouse model, which replicates many DES-related effects seen in humans, suggests that prenatal DES exposure causes alterations that may affect the next generation of offspring. We asked women participating in a large, multi-centre study of prenatal DES exposure to report birth defects occurring among 4029 sons and 3808 daughters (i.e., the third generation). A subcohort of 793 third generation daughters was also queried for birth defects. We used logistic regression models to generate odds ratio and 95% confidence intervals for the association between prenatal DES exposure in the mother and birth defects in the offspring. Based on the mothers' reports, overall birth defects were elevated in the sons (OR = 1.53; 95% CI = 1.04, 2.23) and in the daughters (OR = 2.35; 95% CI = 1.44, 3.82). Most estimates of association were imprecise, but daughters appeared to have an excess of heart conditions (OR = 4.56; 95% CI = 1.27, 16.34). Our data suggest a possible association between the mother's prenatal DES exposure and birth defects in their offspring, particularly in daughters. We cannot, however, rule-out the possible influence of reporting bias. In particular, the exposed daughters' elevated risk of cardiac defects may be as a result of the underreporting of these conditions by unexposed mothers.

We used Cox regression analyses to assess mortality outcomes in a combined cohort of 7675 women who received diethylstilbestrol (DES) through clinical trial participation or prenatal care. In the combined cohort, the RR for DES in relation to all-cause mortality was 1.06 (95% CI = 0.98-1.16), and 1.11 (95% CI = 1.02-1.21) after adjusting for covariates and omitting breast cancer deaths. The RR was 1.07 (95% CI = 0.94-1.23) for overall cancer mortality, and remained similar after adjusting for covariates and omitting breast cancer deaths. The RR was 1.27 (95% CI = 0.96-1.69) for DES and breast cancer, and 1.38 (95% CI=1.03-1.85) after covariate adjustment. The RR was 1.82 in trial participants and 1.12 in the prenatal care cohort, but the DES-cohort interaction was not significant (P = 0.15). Diethylstilbestrol did not increase mortality from gynaecologic cancers. In summary, diethylstilbestrol was associated with a slight but significant increase in all-cause mortality, but was not significantly associated with overall cancer or gynaecological cancer mortality. The association with breast cancer mortality was more evident in trial participants, who received high DES doses.

In 1983-87, we conducted a population-based case-control study of breast cancer in Asian women living in California and Hawaii, in which migration history (a composite of the subject's place of birth, usual residence in Asia (urban/rural), length of time living in the West, and grandparents' place of birth) was associated with a six-fold risk gradient that paralleled the historical differences in incidence rates between the US and Asian countries. This provided the opportunity to determine whether endogenous hormones vary with migration history in Asian-American women. Plasma obtained from 316 premenopausal and 177 naturally premenopausal study controls was measured for levels of estrone (E1), estradiol (E2), estrone sulphate (E1S), androstenedione (A), testosterone (T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), progesterone (PROG) and sex hormone-binding globulin (SHBG). Levels of the oestrogens and sex hormone-binding globulin did not differ significantly between Asian- and Western-born women, although among premenopausal women, those least westernised had the lowest levels of E1, E2, and E1S. Androgen levels, particularly DHEA, were lower in women born in the West. Among premenopausal women, age-adjusted geometric mean levels of DHEA were 16.5 and 13.8 nmol l(-1) in Asian- and Western-born women respectively; in postmenopausal women these values were 11.8 and 9.2 nmol l(-1), (P<0.001) respectively. Among postmenopausal women, androgens tended to be highest among the least westernised women and declined as the degree of westernisation increased. Our findings suggest that aspects of hormone metabolism play a role in population differences in breast cancer incidence., (Copyright 2002 Cancer Research UK)

Although it is well established that women exposed to diethylstilbestrol in utero have an increased risk of spontaneous abortion, ectopic pregnancy, and preterm delivery, it is not known whether they also have an increased risk of infertility. The authors assessed this question in data from a collaborative follow-up study of the offspring of women who took diethylstilbestrol during pregnancy. In 1994, 1,753 diethylstilbestrol-exposed and 1,050 unexposed women from an ongoing cohort study (National Cooperative Diethylstilbestrol Adenosis Study and Dieckmann cohorts) provided data on difficulties in conceiving and reasons for the difficulty. Age-adjusted relative risks were computed for the association of diethylstilbestrol exposure with specific types of infertility. A greater proportion of exposed than unexposed women were nulligravid (relative risk (RR) = 1.3, 95% confidence interval (CI): 1.1, 1.5), and a greater proportion had tried to become pregnant for at least 12 months without success (RR = 1.8, 95% CI: 1.6, 2.1). Diethylstilbestrol exposure was significantly associated with infertility due to uterine and tubal problems, with relative risks of 7.7 (95% CI: 2.3, 25) and 2.4 (95% CI: 1.2, 4.6), respectively. The present findings indicate that diethylstilbestrol-exposed women have a higher risk of infertility than do unexposed women and that the increased risk of infertility is primarily due to uterine or tubal problems.

Background: An association between prenatal diethylstilbestrol (DES) exposure and cancer in men, especially testicular cancer, has been suspected, but findings from case-control studies have been inconsistent. This study was conducted to investigate the association between prenatal DES exposure and cancer risk in men via prospective follow-up., Methods: A total of 3613 men whose prenatal DES exposure status was known were followed from 1978 through 1994. The overall and site-specific cancer incidence rates among the DES-exposed men were compared with those of the unexposed men in the study and with population-based rates. The relative rate (RR) was used to assess the strength of the association between prenatal DES exposure and cancer development. All statistical tests were two-sided., Results: Overall cancer rates among DES-exposed men were similar to those among unexposed men (RR = 1.07; 95% confidence interval [CI] = 0.58 to 1.96) and to national rates (RR = 0.99; 95% CI = 0.65 to 1.44). Testicular cancer may be elevated among DES-exposed men, since the RRs for testicular cancer were 3.05 (95% CI = 0.65 to 22.0) times those of unexposed men in the study and 2.04 (95% CI = 0.82 to 4.20) times those of males in the population-based rates. The higher rate of testicular cancer in the DES-exposed men is, however, also compatible with a chance observation., Conclusions: To date, men exposed to DES in utero do not appear to have an increased risk of most cancers. It remains uncertain, however, whether prenatal DES exposure is associated with testicular cancer.

Objective: Although clinical reports have raised concern that breast implants may either increase the risk of breast cancer or delay its diagnosis, epidemiologic studies have generally shown implant recipients to be at a reduced risk of subsequent breast cancer. A large retrospective cohort study was undertaken to clarify effects of cosmetic breast implantation., Methods: Medical records of 13,488 women receiving cosmetic implants at 18 plastic surgery practices and a group of 3936 patients who received other types of plastic surgery at the same practices were reviewed and information abstracted. Questionnaires were sent to all subjects located as alive, with 71% being completed. Attempts were made to obtain medical verification for all reported cancers and to obtain death certificates for deceased subjects., Results: A total of 136 breast cancers were observed among the breast implant patients. External analyses, using general population rates from the Surveillance, Epidemiology and End Results (SEER) program, resulted in 152.2 cases expected and a standardized incidence ratio (SIR) of 0.9 (95% CI 0.8-1.1). A comparable SIR was found for the other plastic surgery patients (SIR =1.0, 95% CI 0.7-1.2). Internal analyses, directly comparing the implant patients with the other plastic surgery patients, showed a RR of 0.8 (95% CI 0.6-1.1). In neither the external nor internal analyses was there any systematic variation in risk by age or calendar year of initial implant. Risk also did not vary by years of follow-up or by type of implant. Risk was not affected by exclusion of patients who received their implants following surgery for benign breast disease. Although breast tumors tended to be detected at a somewhat later stage among the breast implant than the comparison patients, the difference was not statistically significant, nor was there any significant difference in breast cancer mortality between the two groups., Conclusions: Breast implants do not appear to alter the risk of subsequent breast cancer.

Objectives: This study examined the relation between socioeconomic status (SES) and risk of multiple myeloma among Blacks and Whites in the United States., Methods: This population-based case-control study included 573 cases (206 Blacks and 367 Whites) with new diagnoses of multiple myeloma identified between August 1, 1986, and April 30, 1989, and 2131 controls (967 Blacks and 1164 Whites) from 3 US geographic areas. Information on occupation, income, and education was obtained by personal interview., Results: Inverse gradients in risk were associated with occupation-based SES, income, and education. Risks were significantly elevated for subjects in the lowest categories of occupation-based SES (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.16, 2.53), education (OR = 1.36, 95% CI = 1.06, 1.75), and income (OR = 1.43, 95% CI = 1.05, 1.93). Occupation-based low SES accounted for 37% of multiple myeloma in Blacks and 17% in Whites, as well as 49% of the excess incidence in Blacks. Low education and low income accounted for 17% and 28% of the excess incidence in Blacks, respectively., Conclusions: Our results indicate that the measured SES-related factors account for a substantial amount of the Black-White differential in multiple myeloma incidence.

We evaluated 18,014 patients who underwent allogeneic bone marrow transplantation (BMT) at 235 centers worldwide to examine the incidence of and risk factors for posttransplant lymphoproliferative disorders (PTLD). PTLD developed in 78 recipients, with 64 cases occurring less than 1 year after transplantation. The cumulative incidence of PTLD was 1.0% +/- 0.3% at 10 years. Incidence was highest 1 to 5 months posttransplant (120 cases/10,000 patients/yr) followed by a steep decline to less than 5/10,000/yr among >/=1-year survivors. In multivariate analyses, risk of early-onset PTLD (<1 year) was strongly associated (P <.0001) with unrelated or human leukocyte antigen (HLA) mismatched related donor (relative risk [RR] = 4.1), T-cell depletion of donor marrow (RR = 12.7), and use of antithymocyte globulin (RR = 6.4) or anti-CD3 monoclonal antibody (RR = 43.2) for prophylaxis or treatment of acute graft-versus-host disease (GVHD). There was a weaker association with the occurrence of acute GVHD grades II to IV (RR = 1.9, P =.02) and with conditioning regimens that included radiation (RR = 2.9, P =.02). Methods of T-cell depletion that selectively targeted T cells or T plus natural killer (NK) cells were associated with markedly higher risks of PTLD than methods that removed both T and B cells, such as the CAMPATH-1 monoclonal antibody or elutriation (P =.009). The only risk factor identified for late-onset PTLD was extensive chronic GVHD (RR = 4.0, P =.01). Rates of PTLD among patients with 2 or >/=3 major risk factors were 8.0% +/- 2.9% and 22% +/- 17.9%, respectively. We conclude that factors associated with altered immunity and T-cell regulatory mechanisms are predictors of both early- and late-onset PTLD.

In a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible complication of the tumour. A significant positive trend in risk with increasing years prior to diagnosis of pancreatic cancer was apparent (P-value for test of trend = 0.016), with diabetics diagnosed at least 10 years prior to diagnosis having a significant 50% increased risk. Those treated with insulin had risks similar to those not treated with insulin (odds ratio (OR) = 1.6 and 1.5 respectively), and no trend in risk was associated with increasing duration of insulin treatment. Cholecystectomy also appeared to be a risk factor, as well as a consequence of the malignancy. Subjects with a cholecystectomy at least 20 years prior to the diagnosis of pancreatic cancer experienced a 70% increased risk, which was marginally significant. In contrast, subjects with a history of duodenal or gastric ulcer had little or no elevated risk (OR = 1.2; confidence interval = 0.9-1.6). Those treated by gastrectomy had the same risk as those not receiving surgery, providing little support for the hypothesis that gastrectomy is a risk factor for pancreatic cancer. A significant 40% reduced risk was associated with hay fever, a non-significant 50% decreased risk with allergies to animals, and a non-significant 40% reduced risk with allergies to dust/moulds. These associations, however, may be due to chance since no risk reductions were apparent for asthma or several other types of allergies. In addition, we observed significantly increased risks for subjects reporting a first-degree relative with cancers of the pancreas (OR = 3.2), colon (OR = 1.7) or ovary (OR = 5.3) and non-significantly increased risks for cancers of the endometrium (OR = 1.5) or breast (OR = 1.3). The pattern is consistent with the familial predisposition reported for pancreatic cancer and with the array of tumours associated with hereditary non-polyposis colon cancer.

Prostate cancer is the most common malignancy in men in the United States, with substantially higher rates among American blacks than whites. We carried out a population-based case-control study in three geographic areas of the United States to evaluate the reasons for the racial disparity in incidence rates. A total of 932 men (449 black men and 483 white men) who had been newly diagnosed with pathologically confirmed prostate cancer and 1201 controls (543 black men and 658 white men) were interviewed in person to elicit information on potential risk factors. This report evaluates the impact of dietary factors, particularly the consumption of animal products and animal fat, on the risk of prostate cancer among blacks and whites in the United States. Increased consumption (grams/day) of foods high in animal fat was linked to prostate cancer (independent of intake of other calories) among American blacks [by quartile of intake, odds ratio (OR) = 1.0 (referent), 1.5, 2.1, and 2.0; Ptrend = 0.007], but not among American whites [by quartile of intake, OR = 1.0 (referent), 1.6, 1.5, and 1.1; Ptrend = 0.90]. However, risks for advanced prostate cancer were higher with greater intake of foods high in animal fat among blacks [by quartile of intake, OR = 1.0 (referent), 2.2, 4.2, and 3.1; Ptrend = 0.006] and whites [by quartile of intake, OR = 1.0 (referent), 2.2, 2.6, and 2.4; Ptrend = 0.02]. Increased intake of animal fat as a proportion of total caloric intake also showed positive but weaker associations with advanced prostate cancer among blacks (Ptrend = 0.13) and whites (Ptrend = 0.08). No clear associations were found with vitamin A, calcium, or specific lycopene-rich foods. The study linked greater consumption of fat from animal sources to increased risk for prostate cancer among American blacks and to advanced prostate cancer among American blacks and whites. A reduction of fat from animal sources in the diet could lead to decreased incidence and mortality rates for prostate cancer, particularly among American blacks.

Evidence from case-control studies suggests, although not entirely consistently, that soy intake may protect against breast cancer. The designs and findings of studies conducted in Asian women living in Japan, Singapore, China, and the United States are reviewed. Because of the considerably higher intake of soy by native Asians than by Asian Americans living in California and Hawaii, these studies investigated different segments of the dose-response relation between soy intake and breast cancer risk. Data are not sufficient to determine the amount or frequency of soy intake effective in protecting against breast cancer. Of concern is that soy intake may be homogeneously high in Asia, making it difficult to identify differences in breast cancer risk between high and moderate daily consumers. In studies conducted in Asian Americans, it is difficult to be certain that soy intake is not a marker of other factors related to Western lifestyle that are causally associated with risk of breast cancer. Additional studies assessing the role of soy and breast cancer are needed. These studies should assess intake of all food sources of soy, considering portion size as well as other dietary and nondietary factors that may confound the soy-breast cancer association. A better understanding of the mechanisms whereby soy intake may influence the risk of breast cancer is also needed. Dietary intervention studies with soy will provide information on the acute effects of soy on endogenous hormone concentrations. Cross-sectional and longitudinal studies are necessary to investigate the longer-term relations between hormone concentrations and soy intake in women.

Background: The relationship between diet and pancreatic cancer remains unclear. In this study, we assessed the role of diet and nutrition as risk factors for pancreatic cancer, using data obtained from direct interviews only, rather than data from less reliable interviews with next of kin. We evaluated whether dietary factors could explain the higher incidence of pancreatic cancer experienced by black Americans compared with white Americans., Methods: We conducted a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and 10 New Jersey counties from August 1986 through April 1989. Reliable dietary histories were obtained for 436 patients and 2003 general-population control subjects aged 30-79 years., Results: Obesity was associated with a statistically significant 50%-60% increased risk of pancreatic cancer that was consistent by sex and race. Although the magnitude of risk associated with obesity was identical in blacks and whites, a higher percentage of blacks were obese than were whites (women: 38% versus 16%; men: 27% versus 22%). A statistically significant positive trend in risk was observed with increasing caloric intake, with subjects in the highest quartile of caloric intake experiencing a 70% higher risk than those in the lowest quartile. A statistically significant interaction between body mass index (weight in kg/height in m2 for men and weight in kg/height in m1.5 for women) and total caloric intake was observed that was consistent by sex and race. Subjects in the highest quartile of both body mass index and caloric intake had a statistically significant 180% higher risk than those in the lowest quartile., Conclusions: Obesity is a risk factor for pancreatic cancer and appears to contribute to the higher risk of this disease among blacks than among whites in the United States, particularly among women. Furthermore, the interaction between body mass index and caloric intake suggests the importance of energy balance in pancreatic carcinogenesis.

Objectives: Endogenous and exogenous estrogens are important in the development of endometrial cancer. Several organochlorine compounds, such as o,p'-DDT, have estrogenic properties. The objective of this case-control analysis was to examine serum concentrations of organochlorine compounds and risk of endometrial cancer., Methods: Analyses were based on a sample of 90 endometrial cancer cases and 90 individually matched community controls from a multicenter case-control study in five geographic regions of the United States. Information on potential confounders, including menstrual and reproductive factors, cigarette smoking, diet, and weight, was obtained by interview., Results: The adjusted relative risk of endometrial cancer in the highest quartile of exposure compared with women in the lowest quartile was 0.7 (95 percent confidence interval [CI] = 0.2-2.0) for p,p'-DDE, and 0.9 for total polychlorinated biphenyls (PCBs) (CI = 0.4-2.5)., Conclusions: These findings do not support the hypothesis that organochlorine compounds are linked to the development of endometrial cancer.

Prostate cancer is the most common malignancy in US men (more than 165,000 cases per annum) and occurs substantially more frequently in blacks than in whites. The causes of this disease are, however, poorly understood. Alcohol consumption, which has been clearly related to malignancies of the upper aerodigestive tract, may also increase risk of cancer at other sites, including the prostate. The authors investigated alcohol use as a risk factor for prostate cancer among US blacks and whites. A population-based, case-control study was carried out among 981 men (479 blacks and 502 whites) with pathologically confirmed prostate cancer diagnosed between August 1, 1986, and April 30, 1989, and 1,315 controls (594 blacks and 721 whites) who resided in Atlanta, Georgia; Detroit, Michigan; and 10 counties in New Jersey, geographic areas covered by three population-based cancer registries. In-person interviews elicited information on alcohol use and other factors possibly related to prostate cancer. Compared with never-users, risk for prostate cancer increased with amount of alcohol drunk (chi2 (trend), p < 0.001), with significantly elevated risks seen for those who had 22-56 drinks per week (odds ratio = 1.4; 95% confidence interval 1.0-1.8) and 57 or more drinks per week (odds ratio = 1.9; 95% confidence interval 1.3-2.7). The finding was consistent among blacks (chi2 (trend), p < 0.01) and whites (chi2 (trend), p < 0.05), and among young and old subjects; it was not restricted to a specific type of alcoholic beverage. In this first large study among US blacks and whites, increased risk for prostate cancer was associated with increased alcohol use. The risk was similar for whites and blacks and could not be attributed to tobacco use or to a number of other potential confounders.

Background: For several decades, mortality from breast cancer has been higher in the northeastern part of the United States than in other regions, particularly the South. Rates have also been somewhat higher in the Midwest and West than in the South, especially among older women. The reasons for these geographic variations are not well understood., Purpose: The objective of this study was to evaluate geographic differences in U.S. breast cancer mortality rates in 1987, after taking into account regional differences in the distribution of recognized breast cancer risk factors (e.g., late age at first live birth) and certain prognostic factors (e.g., mammography use)., Methods: The 1987 breast cancer mortality rates for four regions of the country were obtained from the National Center for Health Statistics. Regional data on the distribution of breast cancer risk factors were obtained from 1987 National Health Interview Cancer Epidemiology Supplement interviews with 9778 white women aged 20-79 years. Regional data on the distribution of mammography use were obtained from 1987 National Health Interview Cancer Control Supplement interviews with 3795 white women aged 50-79 years., Results: Age-adjusted mortality ratios (MRs) among women 50 years and older were 1.15, 1.18, and 1.30 in the West, Midwest, and Northeast, respectively, compared with the South. Corresponding MRs among women 20-49 years old were 1.01, 1.08, and 1.07 in the West, Midwest, and Northeast, respectively, compared with the South. After adjustment for recognized risk factors and certain prognostic factors, MRs among older women were 1.13 (95% confidence interval [CI] = 1.04-1.23), 1.08 (95% CI = 1.01-1.16), and 1.13 (95% CI = 1.04-1.23) in the West, Midwest, and Northeast, respectively, compared with the South. Corresponding MRs among younger women were 0.94 (95% CI = 0.76-1.16), 1.05 (95% CI = 0.92-1.18), and 0.99 (95% CI = 0.86-1.14), respectively., Conclusion: Before adjustment for regional differences in recognized risk factors and prognostic factors, mortality excesses among younger women in the Northeast, Midwest, and West were less than 10% compared with the South. After adjustment, MRs were near unity for all regions. Among older women, the excess mortality was more substantial before adjustment for relevant factors, ranging from 15% in the West to 30% in the Northeast. Approximately 50% of the excesses in the Northeast and Midwest and 10% of the excess in the West could be explained on the basis of regional differences in the prevalence of recognized breast cancer risk factors and prognostic factors. After adjustment for these factors, the magnitude of excess in breast cancer mortality in the Northeast (13%) was comparable to that in the West (13%) but still slightly higher than that in the Midwest (8%).

Background: Few estimates of the fraction of cases of breast cancer attributable to recognized risk factors have been published. All estimates are based on selected groups, making their generalizability to the U.S. population uncertain., Purpose: Our goal was to estimate the fraction of breast cancer cases in the United States attributable to well-established risk factors (i.e., later age at first birth, nulliparity, higher family income, and first-degree family history of breast cancer), using data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study (NHEFS), the survey and follow-up of a probability sample of the U.S. population., Methods: From a cohort of 7508 female participants surveyed in the early 1970s, and followed up between 1982 and 1984 and again in 1987, 193 breast cancer cases were accrued for study. We calculated incidence rates, relative risks (RRs), and population attributable risks (PARs) for breast cancer risk factors and extended our results to the U.S. female population by using sample weights from the NHANES I survey., Results: Our PAR estimates suggest that later age at first birth and nulliparity accounted for a large fraction of U.S. breast cancer cases, 29.5% (95% confidence interval [CI] = 5.6%-53.3%); higher income contributed 18.9% (95% CI = -4.3% to 42.1%), and family history of breast cancer accounted for 9.1% (95% CI = 3.0%-15.2%). Taken together, these well-established risk factors accounted for approximately 47% (95% CI = 17%-77%) of breast cancer cases in the NHEFS cohort and about 41% (95% CI = 2%-80%) in the U.S. population., Conclusions: The RRs for most of these risk factors were modest, but their prevalence as a group was high, leading to estimates that suggest that a substantial proportion of breast cancer cases in the United States are explained by well-established risk factors., Implications: Elucidation of the determinants underlying recognized factors and study of other factors that may confer risk or protection are needed in efforts to advance understanding of breast cancer etiology and to aid in devising strategies for prevention.

A population-based, case-control study of pancreatic cancer based on direct interviews with 307 white and 179 black incident cases and 1164 white and 945 black population controls was conducted in three areas of the United States to determine the role alcohol drinking plays as a risk factor for pancreatic cancer and to estimate the extent to which it may explain the higher incidence of pancreatic cancer in blacks compared to whites. Our findings indicate that alcohol drinking at the levels typically consumed by the general population of the United States is probably not a risk factor for pancreatic cancer. Our data suggest, however, that heavy alcohol drinking may be related to pancreatic cancer risk. Among men, blacks and white who drank at least 57 drinks/week had odds ratios (ORs) of 2.2 [95% confidence interval (CI) = 0.9-5.6] and 1.4 (95% CI = 0.6-3.2), respectively. Among women, blacks who drank 8 to < 21 drinks/week had an OR of 1.8 (95% CI = 0.8-4.0), and those who drank at least 21 drinks/week had an OR of 2.5 (95% CI = 1.02-5.9), but whites with the same levels of alcohol intake experienced no increased risk. Compared to whites, blacks had significantly higher ORs associated with heavy alcohol drinking (> or = 57 drinks/week) in men (P = 0.04) and with moderate-to-heavy drinking (> or = 8 drinks/week) in women (P = 0.03). Additional research is needed to determine whether heavy alcohol drinking is causally related to pancreatic cancer and whether the risk of alcohol-related pancreatic cancer is greater in blacks than in whites.

Given the current explosion of knowledge of the genetics and molecular biology of cancer, the possibility of widespread testing for inherited predisposition to cancer has been raised. The main objective of this study was to assess the effect of inherited predisposition on cancer mortality among the National Academy of Sciences-National Research Council Twin Registry. The twins were white male United States veterans of World War II, who were born during the period 1917-1927. The follow-up period was from 1946 to 1990, and some cause of death was determined with the use of death certificates. We compared concordance for death from cancer among 5690 monozygotic twin pairs to that among 7248 dizygotic pairs. A possible effect of inherited predisposition to death from cancer was considered present if concordance for cancer mortality among monozygotic twin pairs was greater than it was among dizygotic twin pairs. Among monozygotic and dizygotic twins, a total of 1918 cancer deaths was observed. Concordance for death from cancer at all sites among monozygotic twins was higher than it was among dizygotic twins (overall rate ratio, 1.4; 95% confidence interval, 1.0-2.0). For each zygosity group, two or fewer pairs were observed to be concordant for death from cancer of a specific site, with the exception of lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the relation between menopausal estrogen use and all-cause and cause-specific mortality in a cohort of over 49,000 women followed between 1979 and 1989 in the Breast Cancer Detection Demonstration Project (BCDDP) Follow-Up Study. We found a lower all-cause mortality rate among women who took estrogens [rate ratio (RR) = 0.7; 95% confidence interval (CI) = 0.7-0.8], particularly current users (RR = 0.3; 95% CI = 0.2-0.4), than among women who never took them. Additional analyses, however, revealed that women who had recently stopped taking estrogens had a higher all-cause mortality rate than women who had never taken them (RR = 1.4; 95% CI = 1.2-1.7). Women who had recently stopped taking estrogens also had higher mortality rates from circulatory disease (RR = 1.3; 95% CI = 1.0-1.8) and cancer (RR = 1.6; 95% CI = 1.2-2.2) than women who never took them. The most likely explanation for these results is that women stop taking estrogens when they develop symptoms of serious illness. As a consequence of this "healthy estrogen user survivor effect," nonexperimental studies are susceptible to overestimating the benefits of menopausal estrogen use, particularly current use, on mortality.

Prostate cancer occurs more frequently in U.S. blacks than whites. A population-based case-control study which investigated the association with family history of cancer was carried out among 981 men (479 black, 502 white) with pathologically confirmed prostate cancer, diagnosed between August 1, 1986, and April 30, 1989, and 1,315 controls (594 black, 721 white). Study subjects, aged 40-79, resided in Atlanta, Detroit, and 10 counties in New Jersey, geographic areas covered by population-based cancer registries. Prostate cancer risk was significantly elevated among those who reported a history of prostate cancer in first-degree relatives (O.R. = 3.2; 95% C.I.: 2.0-5.0), with blacks and whites having similarly elevated risks. These risks were unchanged by statistical adjustment for job-related socio-economic status, education, income, and marital status. Overall, the ORs associated with history of prostate cancer in fathers and brothers were 2.5 (95% C.I.: 1.5-4.2) and 5.3 (95% C.I.: 2.3-12.5), respectively. Risks associated with a family history of prostate cancer were consistently elevated among younger and older subjects. Only small non-significant excesses of prostate cancer risk were associated with a family history of breast, colorectal, or other cancers. While familial occurrence is a key risk factor for prostate cancer and likely to be genetically based, the similar familial risks among blacks and whites suggest that the ethnic disparity in incidence is influenced by environmental factors.

Prior studies have suggested that the risk of testicular cancer among dizygotic twins may exceed that among monozygotic twins or the general population. Cryptorchidism is associated with testicular cancer and twinship, and therefore might potentially explain the findings of the prior studies. In 1993-1994, when they were 66 to 77 years of age, 14,326 twin individuals in the National Academy of Sciences-National Research Council Twin Registry were interviewed by telephone. A history of testicular cancer was reported by 5 (0.08%) of 5951 monozygotic twins and 11 (0.16%) of 6992 dizygotic twins. Follow-up interviews concerning testicular cancer risk factors and treatment were able to be administered to 4 of the monozygotic and 9 of the dizygotic twins reporting testicular cancer. A history of cryptorchidism was reported in the follow-up interview by only one dizygotic twin. Our data agree with the results of prior studies reporting a more frequent occurrence of testicular cancer among dizygotic than monozygotic twins. Although somewhat limited by small numbers, our study also suggests that the findings of increased testicular cancer in dizygotic twins are not explained simply by increased occurrence of cryptorchidism in twins.

Background: In the United States, incidence rates of squamous cell esophageal cancer are more than five times higher among black men than among white men. Reasons that might explain this large racial disparity are being sought., Purpose: We evaluated whether differential use of alcohol and tobacco can fully account for the excess of squamous cell esophageal cancer among U.S. blacks., Methods: We conducted a population-based, case-control study with in-person interviews with 373 squamous cell esophageal cancer case patients (124 white males and 249 black males) and 1364 control subjects (750 white males and 614 black males) from three U.S. geographic areas. Histologically confirmed cases of squamous cell esophageal cancer newly diagnosed from August 1, 1986, through April 30, 1989, among white and black men aged 30-79 years were included., Results: Alcohol use of more than one drink per day and/or current cigarette use of at least one pack per day accounted for 92.7% (95% confidence interval [CI] = 86.8%-98.5%) of the squamous cell esophageal cancers in blacks, versus 86.3% (95% CI = 75.5%-97.1%) in whites, and for 94% of the difference between the black and white annual incidence rates. The interaction between race and the continuous drinking/smoking variable in a logistic regression analysis was statistically significant (two-sided, P = .02). Exposure rates among controls at all levels of combined alcohol and tobacco use examined were slightly higher among blacks and accounted for a small portion of the racial differences in incidence rates., Conclusion: Although the vast majority of esophageal cancers in both blacks and whites in our data can be explained by use of alcohol and tobacco, it is not clear why heavy consumption of alcohol and/or tobacco is responsible for 14.9 per 100,000 per year more cases of squamous cell esophageal cancer among blacks than among whites. The differences in the odds ratios appear to account for more of the racial differences in incidence rates than do the prevalences of exposure to alcohol and tobacco alone. The reasons for this apparent racial difference in carcinogenic risk from the same level of alcohol and tobacco use are unknown, but they may include qualitative differences in alcohol consumption, differences in other environmental exposures that interact with alcohol and/or tobacco to modify risks, or differences in susceptibility to these factors.

Epidemiological and molecular epidemiological findings suggest that inherited predisposition may be a component of lung cancer risk and an important modulator of the carcinogenic effects of cigarette smoke. We have carried out a genetic analysis of lung cancer mortality on the National Academy of Sciences/National Research Council Twin Registry. The registry is composed of 15,924 male twin pairs who were born in the USA between 1917 and 1927 and who served in the armed forces during World War II. As evidence for a genetic effect on lung cancer, we required concordance for lung cancer death to be greater among monozygotic than among dizygotic twin pairs. No genetic effect on lung cancer mortality was observed. The ratio of observed to expected concordance among monozygotic twins did not exceed that among dizygotic twins (overall rate ratio 0.75 [95% CI 0.35-1.6]), even though monozygotic twin pairs are more likely to be concordant for smoking than dizygotic twin pairs in this population. A cohort analysis (accounting for age, sex, race, and smoking intensity) of lung cancer mortality found no lung cancer deaths during 300 person-years of follow-up (observed to expected ratio 0 [0-4.09]) among 47 monozygotic twin smokers whose smoking twins had died of lung cancer, even though smoking histories were very similar within twin pairs. In our study, there is little if any effect of inherited predisposition on development of lung cancer. Genetic factors are not likely to be strongly predictive of lung cancer risk in most male smokers older than 50, the age group in which the vast majority of cases occur.

Incident cases of in situ and invasive cutaneous malignant melanoma diagnosed during 1975-90 were identified through the National Cancer Institute's Surveillance, Epidemiology, and End Results program. We studied the 32,868 white subjects diagnosed with melanoma, who were living in nine cancer registry areas covering approximately 10% of the population of the USA. The summer-to-winter ratio, defined as the ratio of the number of melanomas diagnosed during June to August (summer), to the number of melanomas diagnosed during December to February (winter), was determined according to gender, stage, histologic type and anatomic site. Summer-to-winter ratios were 1.47 (95% confidence interval (CI) 1.37-1.58) for in situ; 1.43 (95% CI 1.38-1.48) for local stage; 1.24 (95% CI 1.12-1.38) for regional stage; and 0.95 (95% CI 0.82-1.11) for distant stage melanoma. For the melanomas staged as local at diagnosis (86% of the invasive melanomas staged), a July peak was observed. For each of the major histological types of local stage melanoma, summer-to-winter ratios were significantly elevated in men (range 1.24-1.41) and women (range 1.44-1.90). For the major anatomic sites (including the head and neck, which are exposed throughout the year) of local stage melanoma, summer-to-winter ratios were elevated for men (range 1.28-1.45) and for women (range 1.31-1.75).(ABSTRACT TRUNCATED AT 250 WORDS)

Prostate cancer occurs more frequently in Blacks than Whites in the United States. A population-based case-control study which investigated the association between tobacco use and prostate cancer risk was carried out among 981 pathologically confirmed cases (479 Blacks, 502 Whites) of prostate cancer, diagnosed between 1 August 1986 and 30 April 1989, and 1,315 controls (594 Blacks, 721 Whites). Study subjects, aged 40 to 79 years, resided in Atlanta (GA), Detroit (MI), and 10 counties in New Jersey, geographic areas covered by three, population-based, cancer registries. No excesses in risk for prostate cancer were seen for former cigarette smokers, in Blacks (odds ratio [OR] = 1.1, 95 percent confidence interval [CI] = 0.7-1.5) and in Whites (OR = 1.2, CI = 0.9-1.6), or for current cigarette smokers, in Blacks (OR = 1.0, CI = 0.7-1.4) and in Whites (OR = 1.2, CI = 0.8-1.7). Increases in risk were noted for smokers of 40 or more cigarettes per day, among former (OR = 1.4, CI = 1.0-1.5) and current (OR = 1.5, CI = 1.0-2.4) smokers. Duration of cigarette use and cumulative amount of cigarette use (pack-years) were not associated with prostate cancer risk for Blacks or Whites. By age, only the youngest subjects, aged 40 to 59 years, showed excess risk associated with current (OR = 1.5, CI = 1.0-2.3) and former (OR = 1.7, CI = 1.1-2.6) use of cigarettes, but there were no consistent patterns in this group according to amount or duration of smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

Using data on 1,860 bladder cancer cases and 3,934 population-based controls from the National Bladder Cancer Study, we examined associations between suspected bladder cancer risk factors and tumor stage and grade. Employment in a high-risk occupation was associated with the entire clinical spectrum of bladder cancer rather than a particular tumor stage or grade. For example, relative risks (RR) were similar for noninvasive and invasive disease (1.5 and 1.6, respectively). Cigarette smoking also increased risk of the entire clinical spectrum of bladder cancer, but the more advanced the stage, the stronger the effect. For example, relative risks of noninvasive and invasive bladder cancer for current heavy smokers were 3.0 and 5.2, respectively. Cigarette smoking was associated with higher risk of low-grade than high-grade tumors, once stage of disease was taken into account. Compared with whites, nonwhites were at a lower risk of noninvasive bladder cancer (RR = 0.4) but at similar risk of invasive bladder cancer (RR = 1.1), a pattern indicating racial differences in health practices related to bladder cancer detection. History of urinary tract infections and bladder stones was associated with increasing relative risks for advanced tumor stage. Heavy artificial sweetener use was associated with higher-grade, poorly differentiated tumors. Coffee consumption and family history of bladder cancer were not consistently associated with tumor stage or grade. Overall, different clinical presentations of bladder cancer share most suspected bladder cancer risk factors, including employment in a high-risk occupation and cigarette smoking.

Background: Breast cancer incidence rates have historically been 4-7 times higher in the United States than in China or Japan, although the reasons remain elusive. When Chinese, Japanese, or Filipino women migrate to the United States, breast cancer risk rises over several generations and approaches that among U.S. Whites., Purpose: Our objective was to quantify breast cancer risks associated with the various migration patterns of Asian-American women., Methods: A population-based, case-control study of breast cancer among women of Chinese, Japanese, and Filipino ethnicities, aged 20-55 years, was conducted during 1983-1987 in San Francisco-Oakland, California, Los Angeles, California, and Oahu, Hawaii. We successfully interviewed 597 case subjects (70% of those eligible) and 966 control subjects (75%)., Results: A sixfold gradient in breast cancer risk by migration patterns was observed. Asian-American women born in the West had a breast cancer risk 60% higher than Asian-American women born in the East. Among those born in the West, risk was determined by whether their grandparents, especially grandmothers, were born in the East or the West. Asian-American women with three or four grandparents born in the West had a risk 50% higher than those with all grandparents born in the East. Among the Asian-American women born in the East, breast cancer risk was determined by whether their communities prior to migration were rural or urban and by the number of years subsequently lived in the West. Migrants from urban areas had a risk 30% higher than migrants from rural areas. Migrants who had lived in the West for a decade or longer had a risk 80% higher than more recent migrants. Risk was unrelated to age at migration for women migrating at ages less than 36 years. Ethnic-specific incidence rates of breast cancer in the migrating generation were clearly elevated above those in the countries of origin, while rates in Asian-Americans born in the West approximated the U.S. White rate., Conclusions: Exposure to Western lifestyles had a substantial impact on breast cancer risk in Asian migrants to the United States during their lifetime. There was no direct evidence of an especially susceptible period, during either menarche or early reproductive life., Implications: Because heterogeneity in breast cancer risk in these ethnic populations is similar to that in international comparisons and because analytic epidemiologic studies offer the opportunity to disentangle correlated exposures, this study should provide new insights into the etiology of breast cancer.

A population-based case-control study of bladder cancer (2,982 cases and 5,782 controls) conducted in 10 areas of the United States examined the effect of smoking as a risk factor among Blacks and Whites, after adjustment for occupation and other potential confounders. Although the overall risk for smoking was slightly higher in Blacks than Whites (relative risk = 2.7 and 2.2, respectively), this difference was not statistically significant. Estimation of risk by dose and currency of exposure revealed no consistent racial disparities in smoking-related risks. Race-specific, attributable risk estimates indicated that nearly half of bladder cancers among both Blacks and Whites could have been prevented by elimination of smoking.

Objective: To clarify several unresolved issues regarding the relationship of estrogens to endometrial cancer risk., Methods: We conducted a hospital-based case-control study involving 300 menopausal women newly diagnosed with epithelial endometrial cancer and 207 population controls matched to the cases for age, race, and residence., Results: Estrogen use significantly increased endometrial cancer risk (adjusted relative risk [RR] 3.0, 95% confidence interval [CI] 1.7-5.1). Although both short- and long-term use appeared to elevate the risk of early-stage tumors, an effect of estrogens on late-stage tumors was observed only for long-term use (RR 2.1, 95% CI 0.7-6.4). A small proportion of women reported having used progestogens simultaneously with estrogens, which was associated with a lower risk (RR 1.8) than use of estrogens alone (RR 3.4). Although the highest risks were for recent users of estrogens, persistent excess risks were seen even for those who had discontinued use of 5 or more years. There were no striking relationships according to the type of estrogen or regimen used, and associations with dose were inconsistent, although women who used low-dose preparations exclusively had the lowest risk. Estrogen injections or creams, used by only 5.9 and 5.1% of the subjects, respectively, were not significant risk factors after adjustment for estrogen pill use. Women who were thin or who smoked cigarettes appeared to be most adversely affected by estrogen use. Estrogen users failed to experience the protective effect normally associated with oral contraceptive use., Conclusion: The effect of estrogens on endometrial cancer risk appears to vary both by usage patterns and by patient characteristics.

Objective: Our objective was to evaluate the risk for endometrial cancer in relation to reproductive, menstrual, and medical factors., Study Design: A case-control study of 405 endometrial cancer cases and 297 population controls in five areas of the United States enabled risk to be evaluated., Results: A major risk factor was the absence of a prior pregnancy (relative risk 2.8, 95% confidence interval 1.7 to 4.6). The protective effect of pregnancy appeared to reflect the influence of term births, because spontaneous and induced abortions were unrelated to risk. Among nulliparous women infertility was a significant risk factor, with women having sought medical advice having nearly eight times the risk of those without difficulty conceiving. After adjustment for other reproductive characteristics, age at first birth and duration of breast-feeding were not related to risk., Conclusions: Elevated risks were found for subjects reporting early ages at menarche (relative risk 2.4 for ages < 12 vs > or = 15) and longer days of flow (relative risk 1.9 for > or = 7 vs < 4 days), but there was no relationship with late ages at natural menopause. Height was not associated with risk, but there was a significant relation to weight, with the risk for 200 versus < 125 pounds being 7.2 (95% confidence interval 3.9 to 13.3). After adjustment for weight and other factors, histories of hypertension and gallbladder disease were not significantly related to risk, but an effect of diabetes persisted (relative risk 2.0, 95% confidence interval 1.1 to 3.6). Hirsutism developing at older ages was also significantly related (relative risk 2.0, 95% confidence interval 1.2 to 3.4).

Proto-oncogenes (H-ras-1 and L-myc) and tumor-suppressor gene (p53) loci have been implicated in lung carcinogenesis. DNA restriction fragment length polymorphisms at these gene loci are being evaluated in a case-control study as markers predictive of risk for cancer or of prognosis when cancer is present. The cases and controls had a cigarette-smoking history of 40 or more pack years or other abnormalities in pulmonary function tests, their ages were closely matched (64 years for cases and 61 years for controls) and the ratio of Caucasians to African Americans was close to unity (cases, 0.95:1.00, controls, 1.00:0.88). The H-ras-1 gene contains an insertion deletion polymorphism. Inheritance of rare H-ras-1 alleles, defined by MspI digestion, confers a relative risk for lung cancer of 2.0 (95% confidence interval, 0.5-7.3) for Caucasians and 3.2 (0.9-11.6) for African Americans (74 cases, 67 controls). The L-myc gene sequence has a restriction site (EcoR1) polymorphism between the second and third exons. Inheritance of restriction site-present alleles was reported to confer poor prognosis (presence of lymph node metastases) in Japanese lung cancer patients. This hypothesis was tested in both case-control study subjects (56 cases, 55 controls) and additional surgical cases (40), but no evidence was found to support the hypothesis in the U.S. population. The p53 gene is a tumor-suppressor gene that can encode either a proline or an arginine in the 72nd residue. No associations was found between the minor allele (proline) and diagnosis of lung cancer (76 cases, 68 controls).(ABSTRACT TRUNCATED AT 250 WORDS)

The association of oral contraceptive use with liver cancer was examined in a study of 76 deaths from primary liver cancer, 22 deaths from cancer of the intrahepatic bile ducts, and 629 controls among women aged 25 to 49 years. The subjects in the study are from the 1986 National Mortality Followback Survey, which included a questionnaire sent or administered to the next-of-kin of almost 20,000 deceased individuals in the United States. Information on a number of lifestyle factors was collected, including questions on oral contraceptive use. Increased risks of primary liver cancer were found for ever-users (odds ratio [OR] = 1.6, 95 percent confidence interval [CI] = 0.9-2.6), and for long-term (greater than or equal to 10 years) users (OR = 2.0, CI = 0.8-4.8) of oral contraceptives. When the analysis was restricted to subjects whose spouse or parent was the respondent, more pronounced risks were seen for ever-users (OR = 2.7, CI = 1.4-5.3) and long-term users (OR = 4.8, CI = 1.7-14.0). No clear excess risk was found for cancer of the intrahepatic bile ducts. This study, the largest to date, adds to the number of investigations demonstrating an increased risk of primary liver cancer with use, particularly long-term use, of oral contraceptives.

To investigate whether parental occupation, especially during the 12 month period before birth, could be responsible for elevated rates of testicular cancer in young men, we used data from a case-control study of 223 cases and 212 controls conducted in the Washington, DC area. For all histologic types of testicular cancer combined, no significant associations were found for specific occupations, nor for the broad occupational categories of professional, other white collar, or blue collar workers. However, for cases with seminomas, excess risks were seen for those with parents employed in the following occupations: mothers in health-related occupations, O.R. = 4.6 (1.1-19.1), and fathers working in automobile service stations, O.R. = 4.0 (0.6-24.5), manufacturing industries, O.R. = 2.2 (1.0-4.2), and aircraft production and maintenance, O.R. = 5.3 (0.7-24.1). Although these findings for seminoma are intriguing, they do not explain the increase of testicular cancer in young men.

A case-control study of 271 testicular cancer cases aged 18-42, including 60 seminomas and 206 other germinal cell tumours, and 259 controls was carried out to study the association between occupation and testicular cancer risk. Study subjects were identified at three medical centres, two of which treat military personnel. Controls were men diagnosed with a cancer other than of the genital tract. Associations were identified between professional employment (administrators, teachers and other professionals) and risk for testicular seminoma, OR = 2.8 (95% Cl: 1.4-5.4) and between employment in production work and risk for other germinal cell tumours, OR = 1.8 (95% Cl: 1.1-2.7). No specific occupations within these broad groups were responsible for observed increases. Self-reported exposure to microwave and other radio waves was associated with an excess risk for both seminomas and other germinal cell tumours. However, an assessment of radio wave exposure based on job title did not support this finding. Although testicular cancer has been increasing in recent decades among young males, occupational factors did not appear to account for a substantial proportion of testicular cancer occurrence in the population studied.

In nearly all populations studied, the risk of bladder cancer is two to four times as great in men as in women. We estimated what the gender-specific incidence rates would be in the absence of exposure to known carcinogenic factors. The data used were obtained from interviews with 2,806 white individuals with bladder cancer and 5,258 white controls in the National Bladder Cancer Study and from incidence data for 1978 from the National Cancer Institute Surveillance, Epidemiology, and End Results Program. The total age-adjusted incidence of bladder cancer was 27.5 cases per 100,000 person-years for men and 7.0 for women, yielding a ratio of 3.9. Even in the absence of exposure to cigarettes, occupational hazards, or urinary tract infection, the gender-related risk persisted; the incidence of bladder cancer was 11.0 in men and 4.1 in women, yielding a ratio of 2.7. Possible explanations for the excessive risk in men include environmental and dietary exposures not yet identified and innate sexual characteristics such as anatomic differences, urination habits, or hormonal factors.

A case-control study of incident invasive cervical cancer was conducted in Birmingham, Alabama; Chicago, Illinois; Denver, Colorado; Miami, Florida; and Philadelphia, Pennsylvania, during 1982-1983. Controls were selected by random-digit dialing and were matched to cases by age, race, and telephone exchange. Of the white, non-Hispanic cases and controls identified, 271 (73%) and 502 (74%), respectively, were successfully interviewed. Diet was assessed by asking about the usual adult frequency of consumption of 75 food items and the use of vitamin supplements. Included were the major sources of the four micronutrients believed to reduce the risk of cervical cancer: carotenoids, vitamin A, vitamin C, and folate. Women in the highest quartiles of intake of each of these micronutrients had adjusted relative risks of invasive squamous cell cervical cancer comparable to those of women in the lowest quartiles, although their micronutrient intake was estimated to be 3-4 times as high. Risk was not affected by increased consumption of vegetables, dark green vegetables, dark yellow-orange vegetables, fruits, or legumes, or by high intake of the basic food groups. These generally negative findings stand in contrast to findings in previous epidemiologic studies, and the discrepancy is not readily explained by bias, uncontrolled confounding, or inadequate power. The question of the role of diet and nutrition in the etiology of cervical cancer is not yet resolved.

The relation between occupation and bladder cancer in women was examined based on data collected during the National Bladder Cancer Study, a population-based, case-control study conducted in 10 areas of the United States. Occupational hazards among women have received little attention in previous bladder cancer studies, in part because most studies have included too few females to accurately estimate risks. In this large case-control study, 652 white female bladder cancer patients and 1,266 white female controls were interviewed to obtain lifetime occupational histories. Patterns of bladder cancer risk by occupation in women tended to be similar to those previously observed among men. Increased risk was apparent for women ever employed in metal working and fabrication occupations (relative risk (RR) = 1.5; 95% confidence interval (CI) 0.9-2.6). Within this summary occupation category, punch and stamping press operatives had a significant trend in risk with increasing duration of employment (p = 0.012); the RR for women employed 5 years or more was 5.6 (95% CI 1.4-26.4). The authors also observed an increased risk for women employed as chemical processing workers (RR = 2.1; 95% CI 0.9-5.1 = with a significant, contrast, a decreased risk was apparent for female textile workers (RR = 0.6; 95% CI 0.3-1.1) with a significant, negative trend in risk with increasing duration of employment (p = 0.031); the relative risk for textile workers employed 10 years or more was 0.4. The authors estimate that 11% of bladder cancer diagnosed among white women in the United States is attributable to occupational exposures; this percentage is considerably lower than the 21-25% previously reported for white men in this study.

We used the population-based tumor registry of Kaiser Permanente in the United States (Portland, OR) to analyze breast cancer incidence from 1960 to 1985. Overall, incidence rose 45% during this period. The largest increases occurred in women 60 years of age or older (74%) and in those 45-59 (36%). The rate in women aged 20-44 has remained essentially unchanged. Localized and regional disease showed similar increases. Review of medical records revealed that only a small portion of this increase was likely to result from increased screening activities. From the increased availability of receptor assays in a large proportion of cases since the mid-1970s, we observed that incidence of estrogen receptor-negative cancers rose 22%-27% between the mid-1970s and the mid-1980s. In contrast, incidence of estrogen receptor-positive tumors increased an average of 131% in the same period, perhaps implicating hormonal factors in the rising incidence of breast cancer.

A historical cohort of 26,561 workers employed in ten facilities was assembled to evaluate cancer risks associated with exposure to formaldehyde. Historical exposures to formaldehyde by job, work area, plant, and calendar time were estimated using monitoring data available from participating plants, comments from long-term workers and company officials, exposure evaluations from walk-through surveys conducted by project industrial hygienists, and results from monitoring specifically performed for this project. A previous report of findings from this study noted a 30% excess mortality from lung cancer among wage workers. The relative risk for lung cancer (whether estimated by SMRs or SRRs) 20 or more years after first exposure did not generally rise with increasing exposure to formaldehyde. Various estimates of exposure were investigated including duration, intensity, peak, cumulative, and average, and by exposures lagged by 5, 10, 20, and 30 years. The excess did not appear to arise gradually, but emerged suddenly among workers whose total cumulative exposure was less than 0.1 ppm-years. Slightly positive, but nonsignificant, exposure-response associations between lung cancer and level of formaldehyde occurred in only a few out of a large number of comparisons (e.g., for persons hired before the start dates for the study and for workers also exposed to particulates). There was a lack of consistency among the various plants for risk of lung cancer, with six plants having elevated SMRs and four plants having deficits. Mortality from lung cancer was more strongly associated with exposure to other substances including phenol, melamine, urea, and wood dust than with exposure to formaldehyde. Workers exposed to formaldehyde without exposure to these substances did not experience an elevated mortality from lung cancer. The risk did not increase with cumulative levels of formaldehyde among those exposed to other substances and there was a slightly negative trend for those exposed to formaldehyde alone. Although some role for formaldehyde, particularly in association with other substances, in the excess of lung cancer seen among these workers cannot be ruled out, these findings suggest that exposure to phenol, melamine, urea, wood dust or other exposures also occurring in the area where these substances were used (i.e., production of resin and molding compounds) may play a more primary role. This association should be further evaluated in other studies that include workers from resin and molding compound operations.

Lifetime patterns of smoking and occupation based on personal interviews were examined among 3,627 white men and 1,200 white women who were randomly selected from ten areas in the United States during the period 1977-1978. These individuals participated in the control series of the National Bladder Cancer Study. We estimated, based on Axelson's method, the extent to which smoking habits for given occupational groups would confound the estimated relative risk for lung cancer for 62 occupations among men and 18 occupations among women. Among men, confounding by smoking resulted in a 30% or greater increased risk of lung cancer in only three occupational groups--namely, stationary engineers and power station operators (relative risk (RR) = 1.6), printers (RR = 1.3), and fishermen and sailors (RR = 1.3). A decrease in lung cancer risk of 0.8 or less due to smoking habits was observed among the clergy (RR = 0.5) and chemical workers (RR = 0.7). Among women, a 30% increase or greater in the risk of lung cancer based on smoking habits alone was found for food service workers (RR = 1.5), building managers and administrators (RR = 1.3), telephone and telegraph operators (RR = 1.3), and operatives (RR = 1.3). A risk ratio of 0.8 or less was observed for those women employed as farmers (RR = 0.5) and teachers (RR = 0.8). Smoking habits by duration of employment were also examined for 38 occupations among men. The largest increase in the risk of lung cancer based on the smoking habits among long-term workers was only 1.3 and was observed for those men employed 20 or more years as painters and as electricians. These findings suggest that the smoking patterns, in only a few occupational groups that we evaluated, confound estimates of the relative risk by more than 30%, and for most occupational groups under investigation in this study, confounding by smoking alone did not produce trends in relative risks by duration of employment.

We investigated the relation between alcohol consumption and breast cancer in the Epidemiologic Follow-up Study of the first National Health and Nutrition Examination Survey, a cohort study based on sample of the U.S. population. A total of 7188 women 25 to 74 years of age who were examined during the period 1971 through 1975 were included in the analysis. Information about alcohol consumption was obtained during the base-line interview. The median follow-up period for this cohort was 10 years. One hundred twenty-one cases of breast cancer that developed after the baseline examination were identified through hospital records or death certificates. The relative-risk estimate for any amount of drinking relative to no drinking was 1.5 (95 percent confidence interval, 1.1 to 2.2). The estimates for three levels of consumption, from the lowest to the highest, were 1.4 (confidence interval, 0.9 to 2.3), 1.5 (0.9 to 2.6), and 1.6 (1.0 to 2.7), in comparison to no drinking at all. These relative-risk estimates were not materially affected by adjustment for known risk factors for breast cancer or for several dietary factors. The results of this study, consistent with those of two other cohort studies and a number of case-control studies, suggest that moderate alcohol consumption is associated with an elevation in the risk of breast cancer of 50 to 100 percent.

In a case-control study, we compared 444 patients with intraocular malignant melanoma with matched controls to evaluate the role of exposure to ultraviolet radiation and other risk factors in the pathogenesis of this tumor. Persons born in the southern United States had a relative risk of 2.7 (95 per cent confidence interval, 1.3 to 5.9) as compared with those born in the North. Subjects with brown eyes were protected as compared with those with blue eyes (relative risk, 0.6; 95 per cent confidence interval, 0.4 to 0.8), but complexion and hair color were not important risk factors. Patients with intraocular malignant melanoma were also more likely to have spent time outdoors in their gardens, to have sunbathed, and to have used sunlamps. Rarely wearing hats, visors, or sunglasses while in the sun was a risk factor for the disease (relative risk, 1.9; 95 per cent confidence interval, 1.6 to 2.2). These data suggest that sunlight exposure is an important risk factor for intraocular melanoma.