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To evaluate the relationship between cumulative lifetime exposure to diagnostic radiation and the risk of multiple myeloma using data from a large, multi-center, population-based case-control study.Study subjects included a total of 540 cases with newly diagnosed multiple myeloma and 1998 frequency-matched population controls living in three areas of the United States (Georgia, Michigan, New Jersey). Information on exposure to diagnostic X-rays was obtained by personal interview.No association was found between case-control status and the total number of reported diagnostic X-rays of any type (odds ratio (OR) for 20 or more compared to less than 5 X-rays = 0.9, 95% confidence interval (95% CI) = 0.7-1.2). There was no evidence of an excess risk of multiple myeloma among individuals who reported exposure to 10 or more diagnostic X-rays that impart a relatively high radiation dose to the bone marrow, as compared to individuals reporting no such exposures (OR 0.7, 95% CI 0.4-1.3).These data suggest that exposure to diagnostic X-rays has a negligible impact, if any, on risk of developing multiple myeloma.

To explore whether dietary factors contribute to the risk of multiple myeloma and the two-fold higher incidence among blacks compared to whites in the United States.Data from a food-frequency questionnaire were analyzed for 346 white and 193 black subjects with multiple myeloma, and 1086 white and 903 black controls who participated in a population-based case-control study of multiple myeloma in three areas of the United States.Elevated risks were associated with obese vs. normal weight (OR = 1.9, 95% confidence interval (CI) = 1.2-3.1 for whites and OR = 1.5, 95% CI = 0.9-2.4 for blacks), while the frequency of obesity was greater for black than white controls. Reduced risks were related to frequent intake of cruciferous vegetables (OR = 0.7, 95% CI = 0.6-0.99) and fish (OR = 0.7, 95% CI = 0.5-0.9) in both races combined, and to vitamin C supplements in whites (OR = 0.6, 95% CI = 0.5-0.9) and blacks (OR = 0.8, 95% CI = 0.5-1.4), with the frequency of vitamin supplement use being greater for white than black controls. However, frequent intake of vitamin C from food and supplements combined was associated with a protective effect in whites (OR = 0.6, 95% CI = 0.4-0.9), but not blacks (OR = 1.2, 95% CI = 0.8-2.1).The greater use of vitamin C supplements by whites and the higher frequency of obesity among blacks may explain part of the higher incidence of multiple myeloma among blacks compared to whites in the United States. In addition, the increasing prevalence of obesity may have contributed to the upward trend in the incidence of multiple myeloma during recent decades.

An increased risk of exposure to pesticides for pancreatic cancer has been suggested in a number of epidemiologic studies.Cases (N = 484), aged 30-79 years, were diagnosed in 1986-1989. Controls (N = 2,095) were a random sample of the general population. Information on usual occupation and potential confounding factors was obtained. A job-exposure matrix (JEM) approach was used to estimate the level of occupational exposure to pesticides.A significant trend in risk with increasing exposure level of pesticides was observed, with ORs of 1.3 and 1.4 for low and moderate/high exposure levels, respectively. Excess risks were found for occupational exposure to fungicides (OR = 1.5) and herbicides (OR = 1.6) in the moderate/high level after adjustment for potential confounding factors. An increased risk for insecticide exposure was disappeared after adjustment for fungicide and herbicide exposures. Results of our occupation-based analysis were consistent with those from the JEM-based analysis.Our results suggest that pesticides may increase risk of pancreatic cancer, and indicate the need for investigations that can evaluate risk by specific chemical exposures. Published 2001 Wiley-Liss, Inc.

In the U.S., the incidence rate of multiple myeloma is more than twice as high for blacks as for whites, but the etiology of this malignancy is not well understood.A population-based case-control interview study of 565 subjects (361 white, 204 black) with multiple myeloma and 2104 controls (1150 white, 954 black) living in 3 areas of the U.S. offered the opportunity to explore whether family history, of cancer contributes to the risk of multiple myeloma and explains the racial disparity in risk.For both races combined, the risk of multiple myeloma was significantly elevated for subjects who reported that a first-degree relative had multiple myeloma (odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.2-12.0). Increased risk was also associated with a family history of any hematolymphoproliferative (HLP) cancer (OR = 1.7, 95% CI = 1.0-2.8), especially in a sibling (OR = 2.3, 95% CI = 1.1-4.5). The risk associated with familial occurrence of HLP cancer was higher for blacks than for whites, but the difference between the ORs was not statistically significant.These data are consistent with previous studies that indicate a familial risk of multiple myeloma, but they explain little of the race-related difference in incidence rates.

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.

To investigate dietary factors for squamous cell esophageal cancer and whether these factors may contribute to the five-fold higher incidence of this cancer in the black versus white population of the United States.Data from a food frequency questionnaire were analyzed for 114 white men and 219 black men with squamous cell esophageal cancer, and 681 white and 557 black male controls from three areas of the United States who participated in a population-based case-control study of esophageal cancer.Protective effects were associated with intake of raw fruits and vegetables (odds ratio for high versus low consumers = 0.3 in both white and black men) and use of vitamin supplements (especially vitamin C; odds ratio for high versus low consumers = 0.4 in both races), with the frequency of consumption of raw fruits and vegetables and vitamin supplements being greater for white than black controls. In addition, elevated risks were associated with high versus low intake of red meat (OR = 2.7 for blacks and 1.5 for whites) and processed meat (OR = 1.6 for blacks and 1.7 for whites), with the levels of consumption being greater for black than white controls.In the United States, these dietary factors may contribute in part to the much higher incidence of squamous cell esophageal cancer among black compared to white men.

In the United States, the incidence rates of multiple myeloma in Blacks are more than twice those in Whites, but the etiology of this cancer is poorly understood. A population-based case-control interview study of 571 subjects (365 White, 206 Black) with multiple myeloma and 2,122 controls (1,155 White, 967 Black) living in three areas of the United States (Georgia, Michigan, New Jersey) offered the opportunity to investigate the relationship with smoking and alcohol drinking and to evaluate whether these factors might contribute to the excess risk of multiple myeloma in Blacks. For Blacks and Whites of either gender, there were no significantly elevated risks associated with ever use of cigarettes or alcoholic beverages and no consistent patterns with either intensity or duration of use. These data support previous studies indicating that smoking and drinking are not related causally to the risk of multiple myeloma, and thus cannot account for the racial disparity in incidence rates.

To evaluate whether the fivefold greater incidence rate of squamous-cell esophageal cancer in Black compared with White men is due to type of alcoholic beverage consumed or to other qualitative differences in alcohol consumption, we conducted a population-based case-control study with 373 males diagnosed with squamous-cell esophageal cancer (124 Whites and 249 Blacks) and 1,364 male controls (750 Whites and 614 Blacks) from three geographic areas in the United States. Included were all histologically confirmed cases newly diagnosed from 1 August 1986 through 30 April 1989, among White and Black men aged 30 to 79 years. Risks varied to some extent according to type of alcohol used, with beer a stronger contributor in Whites, and wine and liquor stronger contributors in Blacks. However, most of the differences in the odds ratios by type of alcohol and race were eliminated after controlling for average weekly amount of total alcohol consumed. Thus, while alcohol use in all forms is an important risk factor for squamous-cell esophageal cancer in Whites and Blacks, type of alcoholic beverage used does not appear to account for the racial differences in incidence.

The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk about 1.10 Gy.

A survey of published epidemiologic studies from eight journals during 1971 to 1990 was conducted to assess the proportion and characteristics of occupational cancer studies that have included women and minorities. A total of 1233 reports included 562 (46%) with subjects limited to white men. The remaining 671 (54%) had subjects from other race-gender groups. Thirty-five percent included white women, but only 14% presented any analyses of white women specifically and only 7% presented more than five risk estimates. The proportions with analyses of nonwhite women (any = 2%; detailed = 1%) or men (any = 7%; detailed = 3%) were also small. Studies with detailed analyses of women and minorities tended to use weaker methodologies (ie, proportionate mortality or cross-sectional design) than the studies of white men and were less able to provide convincing data on the occupational cancer risks of women and minorities.

Examination of risk factors that may be responsible for the increasing incidence of non-Hodgkin's lymphoma (NHL) over the past few decades would be incomplete without considering familial aggregation of hematolymphoproliferative neoplasms and the relative contributions of heredity and environment to the etiology of NHL. Reports of families with two or more NHL cases and sometimes additional members affected by other hematopoietic malignancies (multiple-case families) are summarized, as are findings from surveys and quantitative risk estimates from population-based studies of familial aggregation. The notable occurrence of various immunological abnormalities among multiple-case family members with and without NHL or related neoplasms is underscored, as is the diversity of types of other lymphoproliferative and hematopoietic malignancies among close relatives in these families. Preliminary evidence suggesting that multiple-case families may be more susceptible to certain environmental exposures is presented. An international registry of such families (particularly those identified in population-based studies) is proposed to clarify the interrelationship of genetic, familial, and environmental factors in the etiology of NHL.

Multiple myeloma is a relatively rare cancer that primarily affects older individuals. In the United States, the highest rates of myeloma are found in black individuals and these rates continue to outpace the rate of myeloma in white individuals. The causes of myeloma are largely unknown. The strongest potential risk factors include radiation and agricultural exposures.

To evaluate the possibility that genetic factors contribute to the excess rates of multiple myeloma among blacks, serological typing of human leukocyte antigens (HLA) was conducted for black and white male patients and controls who participated in a large population-based case-control interview study. Forty-six black cases, 88 black controls, 85 white cases, and 122 white controls were typed for the Class I antigens (HLA-A, -B, -C) and for the Class II antigens (HLA-DR, HLA-DQ). Black cases had significantly higher gene frequencies than black controls for Bw65, Cw2, and DRw14, while white cases had higher gene frequencies than white controls for A3 and Cw2 and blanks at the DR and DQ loci. Further analysis of the association between Cw2 and multiple myeloma revealed relative risks of 5.7 (95% confidence interval = 1.5-26.6) and 2.6 (95% confidence interval = 1.0-7.2) for blacks and whites, respectively. The frequency of Cw2 in black and white controls was similar. These findings suggest that the Cw2 allele enhances the risk of myeloma in blacks and whites but do not explain the higher incidence of this cancer among blacks. The study also suggests that undefined DQ antigens may play an etiological role, supporting the need for further research into the immunogenetic determinants of myeloma.

Racial variations in the incidence of various cancer types can provide important etiologic leads for epidemiologists to pursue. The fact that multiple myeloma is the only hematopoietic malignancy which occurs more frequently among U.S. blacks than whites has been especially intriguing to researchers at the National Cancer Institute. To investigate reasons for the black-white differences in risk for multiple myeloma (and three other cancer types), a large-scale epidemiologic study was initiated in 1985. This study was a collaborative endeavor involving the National Cancer Institute, the Georgia Center for Cancer Statistics, the Michigan Cancer Foundation, and the New Jersey State Health Department.

Structural chromosome aberrations were evaluated in peripheral blood samples obtained from three populations exposed to partial-body irradiation. These included 143 persons who received radiotherapy for enlarged thymus glands during infancy and 50 sibling controls; 79 persons irradiated for enlarged tonsils and 81 persons surgically treated for the same condition during childhood; and 77 women frequently exposed as young adults to fluoroscopic chest X rays during lung collapse treatment for tuberculosis (TB) and 66 women of similar ages treated for TB with other therapies. Radiation exposures occurred 30 and more years before blood was drawn. Doses to active bone marrow averaged over the entire body were 21, 6, and 14 cGy for the exposed thymic, tonsil, and TB subjects, respectively. Two hundred metaphases were scored for each subject, and the frequencies of symmetrical (stable) and asymmetrical (unstable) chromosome aberrations were quantified in 97,200 metaphases. Cells with stable aberrations were detected with greater frequency in the irradiated subjects compared with nonirradiated subjects in all three populations, and an overall test for an association between stable aberrations and partial-body ionizing radiation was highly significant (P less than 0.001). We found no evidence that radiation-induced aberrations varied by age at exposure. These data show that exposure of children or young adults to partial-body fractionated radiation can result in detectable increased frequencies of stable chromosome aberrations in circulating lymphocytes 30 years later, and that these aberrations appear to be informative as biological markers of population exposure.

A case-control study of 271 men with testicular cancer and 259 controls was conducted in the Washington, DC area to evaluate whether suggested risk factors could be responsible for the epidemic increases in testicular cancer in young men. No substantial risks were associated with a history of groin hernia operation, the common childhood diseases, allergies, x rays below the waist, venereal disease, vasectomy, or external means of elevating the temperature of the testis. Excess risks were associated with a history of undescended testis (RR = 3.7, CI = 1.5-9.5), testicular trauma (RR = 2.6, CI = 1.6-4.2), and mumps orchitis (RR = 5.8, CI = 0.7-129.7). It is unlikely, however, that any of these conditions has increased sufficiently over time to markedly affect the testicular cancer incidence patterns. Therefore, while the risk factors identified in this paper are of epidemiological interest, they do not account for the increase in testicular cancer in young men.

A case-control study involving interviews with the next of kin or close friends of 120 black males who recently died of esophageal cancer and 250 similarly aged black males who died of other causes was undertaken to discover reasons for the exceptionally high mortality from this cancer in Washington, D.C. The age-adjusted annual death rate in Washington, D.C., for nonwhite males, 1970-75, was 28.6/100,000, far higher than the national rate of 12.4/100,000 and the rates in other metropolitan areas of the country. The major factor responsible for the excess was alcoholic beverage consumption, with an estimated 81% of the esophageal cancers attributed to its use; high use of alcoholic beverages was also found among the controls. The relative risk (RR) of esophageal cancer associated with use of alcoholic beverages was 6.4 (95% confidence interval=2.5, 16.4). The RR increased with amount of ethanol consumed and was highest among drinkers of hard liquor, although the risk was also elevated among consumers of wine and/or beer only. The RR associated with cigarette smoking was 1.9 (1.0, 3.5) when controls with smoking-related causes of death were excluded but declined to 1.5 (0.7, 3.0) when adjusted for ethanol consumption. Significant differences of approximately twofold were found between low and high levels of a) consumption of fresh or frozen meat and fish, fruits and vegetables, and dairy products and eggs and b) relative weight (wt/ht2). The inverse trends with these general measures of nutritional status were not explained by alcoholic beverage consumption or socioeconomic status as measured by educational level.

Incidence data from the Connecticut Tumor Registry for the years 1935-1975 were examined for changing patterns in the rates of thyroid cancer and its four major cell types. Both males and females exhibited a 5-fold increase in age-adjusted thyroid cancer rates over the 41 years, with a nearly constant female:male ratio of 3:1. Papillary and follicular carcinomas were the cell types responsible for the upward trend. Birth cohort analysis revealed cohort effects, especially for females with papillary carcinoma. Age-specific incidence curves for the cohorts born after 1910 showed progressive increases in slope until the 1960 cohort, when the slope decreased. This pattern coincides with the widespread use of radiation therapy for benign conditions of the head and neck among children and adolescents from the early 1920s to the late 1950s. Fitting a logistic model to these data produced relative risks for successive birth cohorts which were consistent with the effects of radiation exposure.

In an attempt to determine the risk factors responsible for the dramatic increases in testicular cancer incidence in young adults, mothers of testicular cancer cases and controls were questioned about in utero exposures, pregnancy-related conditions, and perinatal factors during their pregnancies with the 202 cases and the 206 controls. The strongest risk factor was low birth weight with a greater than 12-fold risk (confidence interval = 2.8 to 78.1) for subjects weighing 5 lb or less at birth compared to those who weighed over 5 lb. A statistically significant 2-fold increase in risk was associated with unusual bleeding or spotting during pregnancy, regardless of whether medication was taken for this condition. Other exposures during pregnancy associated with a statistically significant increase in risk were: use of "sedatives"; alcohol consumption; and exposure to X-rays. No excess risk was associated with the use of hormones during pregnancy. The findings for birth weight and abnormal uterine bleeding suggest that significant compromise of the normal maternal-fetal environment may be associated with subsequent increase in risk of testicular cancer. However, this increase in risk is not great enough to explain the dramatic increases in testicular cancer that have occurred in young adults.

A case-control study of esophageal cancer was conducted among the black male residents of Washington, D.C., to find reasons for the exceptionally high risk in this population. The next of kin of 120 esophageal cancer cases who died during 1975-77 and of 250 D.C. black males who died of other causes were interviewed. Five indicators of general nutritional status--fresh or frozen meat and fish consumption, dairy product and egg consumption, fruit and vegetable consumption, relative weight (wt/ht2), and number of meals eaten per day--were each significantly and inversely correlated with the relative risk of esophageal cancer. Associations with other food groups were not apparent. The least nourished third of the study population, defined by any of these five measures, was at twice the risk of the most nourished third. None of these associations was markedly reduced by controlling for ethanol consumption, the other major risk factor in this population; smoking; socioeconomic status; or the other nutrition measures. When the three food group consumption measures were combined into a single overall index of general nutritional status, the relative risk of esophageal cancer between extremes was 14. Estimates of the intake of vitamin A, carotene, vitamin C, thiamin, and riboflavin were inversely associated with relative risk; but each micronutrient index was less strongly associated with risk than were the broad food groups that provide most of the micronutrient. Thus no specific micronutrient deficiency was identified. Instead, generally poor nutrition was the major dietary predictor of risk and may partially explain the susceptibility of urban black men to esophageal cancer.

The role of cryptorchidism (undescended testis) and inguinal hernia in the etiology of testicular cancer among men aged 18-42 years was evaluated in a case-control study of 271 cases and 259 controls referred to three collaborating medical centers in the Washington, DC, area. The relative risk of testicular cancer for men who reported a history of an undescended testis was 3.7 (95% confidence interval = 1.6-8.6). The risk increased with increasing age at correction; the risk was highest for those men whose cryptorchid testis was never corrected. Among unilateral cryptorchids, no increased risk of testicular cancer was observed for the normally descended testis. There was only a slight excess risk for men without cryptorchidism who had a herniorrhaphy; however, those who underwent a hernia operation after age 7 had a significantly elevated risk of testicular cancer on the same side as the hernia. This case-control study is the first one to support the clinical recommendations for early surgical correction of cryptorchidism and inguinal hernia. Data from this study suggest that the excess cancer risk associated with cryptorchidism is due to internal factors that affect the undescended testis rather than to some underlying developmental abnormality.

Waldenstrom's macroglobulinemia (WM) is a rare disorder of lymphoid and plasma cells characterized by an immunoglobulin M (IgM) monoclonal gammopathy, clinical and immunopathologic similarities with other lymphoproliferative neoplasms, but the etiology of which is unknown. We undertook the first case-control study of this disorder among 65 cases, comprising 87% of all WM patients diagnosed during 1969-1983 in the greater Baltimore, Maryland area. Compared with 213 hospital controls without cancer, cases were slightly better educated, but there were otherwise no differences in sociodemographic factors, history of prior medical conditions, medication use, cigarette smoking, alcohol consumption, specific occupational exposures, employment in any particular industries or occupations, or familial cancer history. Cases were more likely than controls to have first-degree relatives with a history of pneumonia, diphtheria, rheumatic fever, and diabetes mellitus. An exploratory evaluation of immunologic profiles of first-degree relatives of 48% of families of cases revealed that relatives of two cases had asymptomatic IgM (750 mg/dl) monoclonal gammopathy and close to 40% of the 109 evaluated had diverse immunologic abnormalities. Larger population-based case-control studies are needed to further evaluate the suggestive evidence of immune dysfunction among families of WM cases.