Epidemiology of the M-component immunoglobulin types of multiple myeloma

The purpose of this population-based case-control study was to learn whether risk factors differ for the individual immunoglobulin types of multiple myeloma. In particular, we sought to determine whether IgA and IgG myeloma were related to a history of exposure to reported IgA- and IgG-stimulating conditions, respectively, or to a history of selected occupational and physicochemical exposures. The M-component immunoglobulin type was determined from immunoelectrophoresis as reported in medical records, and exposure status was obtained through in-person interviews. IgG (56 percent) and IgA (22 percent) M-components predominated. For 17 percent of cases, no peak was found on immunoelectrophoresis; they were presumed to have light-chain myeloma. Persons with these three types of myeloma did not differ with respect to distributions of age or race, but a somewhat higher proportion of light-chain cases were women (58 percent cf 45 percent of all other cases). Detailed analysis of the IgA and IgG subtypes provided little evidence that they differ with respect to prior immune stimulation or employment in several specific jobs. IgA myeloma, but not IgG myeloma, was associated modestly with a history of exposure to chest and dental X-rays. Our study provides little evidence that IgA and IgG myeloma differ with respect to the risk factors examined.Ms Herrinton and Drs Koepsell, Weiss, and Daling are with the Department of Epidemiology, University of Washington, Seattle, WA, USA, and the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Dr Demers is with the Department of Environmental Health, University of Washington, Seattle, WA, USA. Dr Taylor is with Group Health Cooperative of Puget Sound, Seattle, WA, USA. Dr Lyon is with the School of Medicine, University of Utah, Salt Lake City, UT, USA. Dr Swanson is with the Cancer Center, Michigan State University, East Lansing, MI, USA. Dr Greenberg is with the School of Public Health, Emory University, Atlanta, GA, USA. Address correspondence to Ms Lisa Herrinton, Fred Hutchinson Cancer Research Center, 1124 Columbia MP-381, Seattle, WA 98104, USA. The project was supported by grants CA23350, CA39779, and CA09168 from the US National Cancer Institute.     

Liver cancer in Asian migrants to the United States and their descendants

The incidence of primary liver cancer in Chinese, Japanese, and Filipino migrants to the United States and their descendants is compared with that of United States-born Whites. Incident liver cancer cases were ascertained between 1973 and 1986 from population-based cancer registries serving the San Francisco/Oakland (CA) metropolitan area, 13 counties of western Washington, and Hawaii. The population of these three areas, with regard to age, race, and country of birth, was estimated from a special tabulation of the 1980 US census. Rates of primary liver cancer were higher for men born in Asia than Asian men born in the US, who, in turn, had higher rates than did US Whites (respective annual rates per 100,000: Chinese, 26.5 and 9.8; Japanese, 16.5 and 6.6; Filipinos, 11.4 and 6.5; US Whites, 3.4). Among Asian American women, the trends were not as consistent (respective annual rates per 100,000: Chinese, 2.2 and 3.7; Japanese, 1.9 and 1.4; Filipino, 2.6 and 0; US Whites, 1.1). In general, liver cancer incidence among Asian Americans was lower than among residents of Asia. These findings are compatible with substantial variation among Asians in the prevalence of one or more etiologic factors for liver cancer, such as hepatitis-B infection and aflatoxin consumption, in relation to residence and place of birth.Dr Rosenblatt is with the Department of Community Health, University of Illinois, Champaign, IL, USA. Drs Weiss and Schwartz are with the Department of Epidemiology, University of Washington, and Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Address correspondence to Dr Rosenblatt, Department of Community Health, 121 Huff Hall, University of Illinois at Urbana-Champaign, 1206 South Fourth Street, Champaign, IL 61820, USA. This research was supported by grant numbers R35CA39779 and T32CA09168 from the US National Cancer Institute.     

Cutaneous melanoma following cervical intra-epithelial neoplasia in western washington state

Stimulated by a recent report from a Norwegian pathology institute of an excess risk of melanoma among women with cervical neoplasia, we analyzed the relevant data from a population-based cancer registry serving western Washington State (United States). Among 11,693 women diagnosed with cervicalintra-epithelial neoplasia (CIN) between 1974 and 1989 who were followed-up for at least a year, 14 cases of cutaneous melanoma were identified, in comparison with 13.7 cases expected (relative risk=1.0,95 percent confidence interval=0.5-1.7) based on the rates of melanoma among all women who resided in this area. While these results are at odds with those recently reported from the pathology institute, they are similar to those obtained in previous cancer-registry studies in several countries, which found little or no excess occurrence of melanoma following cervical cancer.Authors are with the Department of Epidemiology, University of Washington, Seattle, WA, USA. Drs Weiss and Schwartz are also with the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Address correspondence to Dr Weiss, Department of Epidemiology, SC-36, University of Washington, Seattle, WA 98195, USA. This investigation was supported by PHS grant numbers 5T32 CA09168-17 and R35 CA39779 awarded by the US National Cancer Institute, DHHS.     

A prospective study of cigarette tar yield and lung cancer

We examined the relationship of cigarette tar yield and other cigarette-usage characteristics in current smokers to the incidence of lung cancer in a study population of 79,946 Kaiser Permanente Medical Care Program members, aged 30–89 years, who completed a detailed, self-administered, smoking-habit questionnaire during the years 1979 through 1985. Mean length of follow-up was 5.6 years. There were 302 incident lung cancers, of which 89 percent occurred in current or former smokers. The tar yield of the current cigarette brand was unassociated with lung cancer incidence (relative risk [RR]=1.02 per 1 mg tar-yield in men, 95 percent confidence interval [CI]=0.98–1.05; RR=0.99, CI=0.96–1.03 in women). However, in long-term (>20 years) smokers, the risk of lung cancer was decreased in women who had smoked filtered cigarettes for 20 or more years relative to lifelong smokers of unfiltered cigarettes (RR=0.36, CI=0.18–0.75), but not in men who had smoked filtered cigarettes for 20 or more years (RR=1.04, CI=0.58–1.87).Authors are with the Division of Research, Kaiser Permanente Medical Care Program, 3451 Piedmont Avenue, Oakland, CA 94611, USA. Address correspondence to Dr Sidney. This study was funded by grants R01 CA 36074 and R35 CA 49761 from the US National Cancer Institute.     

Melanoma: linked temporal and latitude changes in the United States

The rise in the incidence and mortality from melanoma of the skin is slowing down in younger age groups in the United States. In many White populations, including that of the US, melanoma incidence and mortality rates increase according to proximity of residence to the Equator. Variations with age in this gradient do not seem to have been examined. We examined how the influence of latitude on melanoma rates varied with age. Estimates of age-specific trends by time and by latitude for natural logarithm (Ln) melanoma incidence-rates from the Surveillance, Epidemiology and End Results (SEER) programs, and Ln melanoma mortality rates from the US Vital Statistics were derived from fitted regression equations. Unexpectedly, a decline from old age to youth in the influence of latitude was found for both incidence and mortality from melanoma of the skin in males, and for mortality in females. Further, these changes in the relationship to latitude with age correlated with the changes in time trends with age. The link with exposure suggests that the time trends in melanoma are driven by variations in damage to melanocytes in early life that increases sensitivity to sunlight. This has implications for the general understanding of melanoma etiology and for health education.Dr Lee is at the School of Public Health, University of Washington, Seattle, WA, USA. Dr Scotto is with the Division of Biostatistics & Epidemiology, Georgetown University, Washington, DC, USA. Address correspondence to Dr Lee, Department of Epidemiology SC 36, School of Public Health, University of Washington, Seattle, WA 98195, USA.     

Thyroid cancer incidence in Asian migrants to the United States and their descendants

We compared incidence rates of primary cancer of the thyroid among United States-born and foreign-born Chinese, Japanese, and Filipino residents of the US with rates among US-born Whites. Thyroid cancers diagnosed between 1973 and 1986 occurring among individuals 15 to 84 years of age residing in western Washington state, the San Francisco-Oakland (California) area, or the state of Hawaii were included in the analysis. Population estimates by age, gender, ethnicity, and country of birth were obtained for these areas from the US Bureau of the Census. Filipino women born in the Philippines had 3.2 (95 percent confidence interval=2.7–3.8) times the rate of thyroid cancer of US-born White women, while US-born Filipino women were not at any increased risk. Philippine-born Filipino men also had a relatively high rate of thyroid cancer (relative risk [RR]=2.6), more so than US-born Filipino men (RR=1.5). Among Japanese, risk of thyroid cancer varied by birthplace, but the direction of the association differed by gender and by histologic type of cancer. No clear association with birthplace was noted among Chinese men or women. These data suggest that persons residing in one or more regions from which Filipino-Americans migrated have been exposed to environmental influences that have increased their subsequent risk of thyroid cancer.This project was supported by grant # R35 CA 39779 from the US National Cancer Institute.     

Determinants of survival following the diagnosis of esophageal adenocarcinoma (United States)

The rapidly rising incidence of esophageal adenocarcinomas in the United States and western Europe remains unexplained. Most persons who develop the disease have had long-standing gastroesophageal reflux symptoms with concomitant Barrett's metaplasia. They are, therefore, potentially identifiable for endoscopic screening and cancer surveillance, which should facilitate the early detection of these tumors. We undertook these analyses to determine the extent to which the opportunity for early diagnosis and treatment of esophageal adenocarcinomas has been realized in the US. Specifically, using data from the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute, we examined changes in stage of disease at diagnosis and in survival between 1973 and 1991 and investigated patient characteristics as predictors of survival. Improvements in stage at diagnosis and in survival between 1973 and 1991 were minor and clinically insignificant; overall five-year survival never exceeded 10 percent. Stage of disease at diagnosis was the strongest determinant of subsequent survival; five-year survival with patients with in situ tumors was 68.2 percent. This survival advantage persisted up to 15 years after diagnosis and was independent of other prognostic factors. We conclude that the opportunity for reduction in esophageal cancer mortality has been largely unrealized in the US. In light of the increasing incidence of esophageal adenocarcinoma, efforts should be devoted to identifying those at highest risk of developing Barrett's metaplasia and subsequent adenocarcinoma, and to developing cost-effective primary prevention and cancer surveillance methods targetting them.Drs Farrow and Vaughan are with the Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, and the Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA. Address correspondence to Dr Farrow at the Program in Epidemiology, Fred Hutchinson Cancer Research Center, 1124 Columbia St., MP-474, Seattle, WA 98104, USA. This work was supported by US NIH grants U01CA57949 and R01CA61202.     

Colorectal cancer and solar radiation

It has been suggested that sunlight might have a role in the prevention of colorectal cancer via a mechanism involving vitamin D. We used data from nine population-based cancer registries in the United States to analyze incidence rates for colon and rectal cancer during 1973–84 as a function of regional variation in the levels of available solar radiation. Data were restricted to include only those persons born and diagnosed in the same state. Incidence rates of colon and rectal cancer among men tended to increase with decreasing levels of solar radiation. Compared to rates in New Mexico and Utah, for example, rates in the Detroit area (MI), Connecticut, and western Washington were 50 percent to 80 percent higher. Among women, colon cancer rates showed a similar trend, though of smaller magnitude; rates of rectal cancer among women did not vary in relation to levels of available solar radiation.Dr Emerson, at the time of this research, was with Dr Weiss at the Department of Epidemiology, University of Washington, School of Public Health and Community Medicine, Seattle, WA and the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Address correspondence to Dr Emerson at her current address: Arizona Cancer Center, Room 2942, University of Arizona, Tucson, AZ 85724, USA. This research was supported in part by Grant No. 1-R35-CA39779 and Grant No. 5-T32-CA09168-13 from the National Cancer Institute.     

Histologic types and hormone receptors in breast cancer in men: a population-based study in 282 United States men

Histologic slides from 282 incident cases of breast cancer in men, that were identified in 10 population-based cancer registries in the United States, were reviewed by a single pathologist. Breast cancer more often presented in the noninvasive stage in men (10.8 percent of all cases) than would be expected among women. All noninvasive carcinomas were of the ductal type. Of invasive carcinomas, compared with women, men had smaller proportions of lobular and mucinous types and larger proportions of ductal and papillary types and Paget's disease. No case of tubular or medullary carcinoma was seen. The breast in men is composed only of ducts and normally contains no lobules, and the histologic types of breast carcinomas that predominate in men are likely of ductal origin. Estrogen and progesterone receptors were present in 86.7 percent and 76.3 percent of invasive carcinomas, respectively, which are higher proportions than would be expected among women. Also, unlike findings in women, receptor content was not associated with patient age at diagnosis.Dr Stalsberg is with the Institute of Medical Biology, University of Tromsø, Tromsø, Norway, and Drs Thomas, Rosenblatt, Jimenez, and McTiernan are with the Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, Authors also are affiliated with the University of Illinois, Champaign, IL, USA (Dr Rosenblatt); the Institutio Regional de Investigacion en Salud Publica, Guadalajara, Mexico (Dr Jimenez); the University of Washington School of Medicine, Seattle, WA, USA (Dr McTiernan); the Pharmaceutical Division, CIBAGEIGY Corp., Summit, NJ, USA (Dr Stembagen); the University of Southern Maine, Portland, ME, USA (Dr Thompson); the Connecticut Cancer Epidemiology Unit, New Haven, CT, USA (Dr McCrea Curnen); the School of Public Health, University of California, Berkeley, CA, USA (Dr Satariano); the Resource for Cancer Epidemiology, Department of Health Services, Emeryville, CA, USA (Dr Austin); the School of Public Health, Emory University, Atlanta, GA, USA (Dr Greenberg); the New Mexico Tumor Registry, Albuquerque, NM, USA (Dr Key); the Epidemiology Program, Cancer Research Center of Hawaii, Honolulu, HI, USA (Dr Kolonel); the Northern California Cancer Center, Alameda, CA, USA (Dr West). Address correspondence to Dr Stalsberg, Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway. This study was funded by grant number RO1 CA35653 from the US National Cancer Institute.     

Incidence of male genital skin tumors: Lack of increase in the United States

In men, genital exposure to ultraviolet radiation (UVR) has been hypothesized to increase the risk of nonmelanotic skin tumors at that site. However, during the period 1973–86, no change in the incidence of penile or scrotal skin tumors occurred in the United States, despite a likely increase in the population's level of genital exposure to UVR through the use of sunlamps and sunbeds. While UVR in conjunction with use of 8-methoxypsoralen by men with psoriasis is clearly related to an increase in the incidence of male genital skin tumors, our data provide no support for the hypothesis that, among men in general, UVR alone has this same effect.Drs Goldoft and Wesiss are with the Department of Epidemiology, SC-36, University of Washington, Seattle, WA 98195 USA. Address correspondence to Dr Weiss. This investigation was supported by PHS grants number 1 R35 CA39779 and 5 T32 CA09168 awarded by the National Cancer Institute, DHHS.     

Colorectal cancer incidence in Asian migrants to the United States and their descendants

Objectives: To examine the incidence of colorectal cancer among Asian residents of the United States according to country of birth. Methods: We determined the incidence of colorectal cancer during 1973–1986 among Asian residents in three areas of the western United States (Hawaii, San Francisco/Oakland SMSA, and western Washington state) in relation to country of birth. Numerators for the rates were obtained from the Surveillance, Epidemiology and End Results (SEER) program; a special tabulation of the 1980 US Census was used to estimate the size and composition of the population at risk. Results: US-born Japanese men experienced incidence rates of colorectal cancer twice as high as foreign-born Japanese men and about 60% higher than those of US-born white men. Incidence among US-born Japanese women was about 40% higher than that among Japanese women born in Japan or US-born white women. Foreign-born Chinese men had about the same incidence of colorectal cancer as US-born white men, while US-born Chinese men experienced slightly reduced rates. Chinese women had rates that were generally 30–40% lower than that of US-born white women, regardless of place of birth. Incidence rates for both US-born and foreign-born Filipinos were 20–50% those of US-born whites. Conclusions: These findings suggest that one or more exposures or characteristics that differ between Japanese migrants and their descendants affect the development of colorectal cancer.     

Risk of endometrial cancer following cessation of menopausal hormone use (Washington, United States)

While there are a number of benefits to the health of postmenopausal women from use of unopposed estrogens, the increased risk of endometrial cancer related to these hormones has led many women to use combined estrogen-progestogen therapy instead, or not to use hormones at all. Most women who take hormones do so only in the early portion of their postmenopausal years, so the risk of endometrial cancer following cessation of use might bear heavily on the overal risk/benefit evaluation. We analyzed data from a case-control study of women in western Washington (United States) to assess the magnitude of excess risk of endometrial cancer following discontinuation of estrogen use. Cases (n=661) consisted of women aged 45 to 74 diagnosed between 1985 and 1991 who resided in one of three counties in Washington State. Controls (n=865) were identified by random-digit dialing. Subjects were interviewed in-person to ascertain current and prior hormone use. The analysis was restricted to women who had not received combined estrogen-progestin therapy. Among women who had used unopposed estrogens at some time, risk of endometrial cancer declined as time since last use increased. Nonetheless, even among women who used these hormones for just a few years, the risk remained elevated by 30 to 70 percent almost a decade after cessation. These results, combined with those of most (but not all) other studies of this issue, suggest that a woman who has discontinued unopposed estrogen therapy may retain a small increased risk of endometrial cancer for a long period of time.Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, the Department of Epidemiology, University of Washington Department of Biostatistics University of Washington, Seattle, WA. Department of Epidemiology, University of Washington, Seattle, WA 98195, USA. This research was supported by US National Cancer Institute contracts R01 CA47749 and R35 CA39779.     

Breastfeeding and breast cancer risk

A population-based case-control study of breast cancer with a focus on premenopausal women under 45 years of age, conducted in three geographic regions of the United States, enabled the evaluation of risk in relation to varying breastfeeding practices. Among premenopausal parous women (1,211 cases, 1,120 random-digit-dialing controls), a history of breastfeeding for two or more weeks was associated with a relative risk (RR) of 0.87 (95 percent confidence interval [CI]=0.7–1.0). This relationship was not altered substantially by removing from the reference group women who had problems with breastfeeding in the first two weeks, including those with insufficient milk production. Risk was not related substantially to number of children breastfed or length of breastfeeding, although a relatively low risk was observed among those breastfeeding for the longest duration examined (RR=0.67, CI=0.4–1.1 for an average period per child of 72 or more weeks). Women who began to breastfeed at a young age (<22 years) experienced the greatest reduction in risk, but other timing parameters (e.g., interval since first or last breastfeeding) were not predictive of risk. Risks were not modified substantially by age or menopause status, although the number of menopausal subjects examined was limited. Use of medications to stop breast milk was unrelated to risk (RR=1.04). The results of this study do not support the notion that breastfeeding substantially reduces breast cancer risk; however, this may reflect the fact that most of our study subjects breastfed only for limited periods of time (average breastfeeding per child of 30 weeks). Further studies are needed to clarify the relationship of breastfeeding to breast cancer risk, and to determine possible etiologic mechanisms underlying any observed associations.Drs Brinton, Potischman, and Swanson are with the Environmental Epidemiology Branch, National Cancer Institute, Betbesda, MD, USA. Authors also are affiliated with the Special Epidemiology Program, New Jersey State Department of Health, Trenton, NJ, USA (Ms Schoenberg); Rollins School of Public Health, Emory University, Atlanta, GA, USA (Dr Coates); the Division of Epidemiology, Columbia University School of Public Health, New York, NY, USA (Dr Gammon); and the Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA (Drs Malone, Stanford, Daling). Address correspondence to Dr Brinton, Environmental Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 443, Bethesda, MS 20892, USA.     

Leukemia,lymphoma, and multiple myeloma following selected medical conditions

The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.Ms Doody and Drs Linet, Pottern, Boice, and Fraumeni are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Glass is with the Kaiser Permanente Medical Care Program, Northwest Region, Portland, Oregon, USA. Dr Friedman is with the Kaiser Permanente Medical Care Program, Northern California Region, Oakland, California, USA. Address correspondence to Ms Doody, Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 408, Bethesda, MD 20892, USA. This research was supported in part by National Cancer Institute contracts NO1-CP-01047, NO1-CP-01054, NO1-CP-11009, NO1-CP-11037, NO1-CP-31035, and NO1-CP-61006.     

A population-based study of contralateral breast cancer following a first primary breast cancer (Washington, United States)

To evaluate predictors of contralateral breast cancer risk, we examined data from a nested case-control study of second primary cancers among a cohort of women in western Washington (United States) diagnosed with breast cancer during 1978 through 1990 and identified through a population-based cancer registry. Cases included all women in the cohort who subsequently developed contralateral breast cancer at least six months after the initial diagnosis, but prior to 1992 (n=234). Controls were sampled randomly from the cohort, matched to cases on age, stage, and year of initial breast cancer diagnosis. Information on potential risk factors for second primary cancer was obtained through medical record abstractions and physician questionnaires. Women who were postmenopausal due to a bilateral oophorectomy (i.e., a surgical menopause) at initial breast cancer diagnosis had a reduction in contralateral breast cancer risk compared with premenopausal women (matched odds ratio [mOR]=0.25, 95 percent confidence interval [CI]=0.09–0.68), whereas no reduction in risk was noted among postmenopausal women who had had a natural menopause (mOR=0.90, CI=0.39–2.09). Among postmenopausal women, there was a suggestion of a lower risk associated with relatively high parity (2+). A family history of breast cancer was associated with an increased risk (mOR=1.96, CI=1.22–5.15) and varied little by menopausal status. Having an initial tumor with a lobular component (c.f. a ductal histology) was not related strongly to risk (mOR=1.47, CI=0.79–2.74). The results of the present and earlier studies argue that we have limited ability to predict the occurrence of a contralateral breast tumor. Better predictors will be required before diagnostic and preventive interventions can be targeted to subgroups of patients with unilateral breast cancer.Authors are with the Department of Epidemiology, University of Washington, Seattle, WA, USA (Drs Cook, White, Schwartz, Daling, Weiss); with the Fred Hutchinson Cancer Research Center, Seattle, WA (Drs Cook, White, Schwartz, McKnight, Daling, Weiss); and the Department of Biostatistics, University of Washington, Seattle, WA (Dr McKnight). Address correspondence to Dr Cook, MP-381, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA 98104, USA. This research was supported in part by grants from the US National Cancer Institute (R35 CA 39779), the Agency for Health Care Policy and Research (1 RO3 HS08004-01), and by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, which is funded by Contract No. N01-CN-05230 from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center.     

Maternal exposure to potential inhibitors of DNA topoisomerase II and infant leukemia (United States): A report from the Children's Cancer Group

Nearly 80 percent of infant leukemias present with an abnormality involving the MLL gene at 11q23. Moreover, secondary acute myeloid leukemias (AML) that occur as the result of chemotherapy agents, which are known to inhibit DNA topoisomerase II, often manifest the same MLL abnormalities. It has been hypothesized that de novo infant leukemias may occur as a result of maternal exposure to agents in diet and medications that inhibit DNA topoisomerase II. Three epidemiologic studies of childhood leukemia with similar methodologies were conducted in the United States and Canada over the past 10 years by the Children's Cancer Group (CCG). Of the total 771 mothers of infants diagnosed at one year of age or less (<12.5 months) who originally were interviewed (303 infant cases and 468 matched controls) across the three studies, follow-up questionnaire data on maternal exposure to potential DNA topoisomerase II inhibitors during pregnancy were available on 84 cases and 97 matched controls in the US. For maternal diet, a composite variable was created that consisted of 10 foods identified a priori as containing DNA topoisomerase II inhibitors. There were no significant trends with increasing maternal consumption for either the overall group, or the acute lymphoblastic leukemia (ALL) stratum. However, within the AML stratum, there was a statistically significant positive association (P trend=0.04) with increasing consumption of DNA topoisomerase II-inhibitor containing foods (odds ratio [OR]=9.8, 95 percent confidence interval [CI]=1.1–84.8; OR=10.2, CI=1.1–96.4; for medium and high consumption, respectively). Other potential topoisomerase II inhibitors were explored; no significant findings were found. Results of this preliminary study, in combination with molecular data, should be used in future investigations of childhood leukemia (particularly, infant) to justify the incorporation of a detailed dietary history.Drs Ross and Robison are with the Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, MN, USA. Dr Potter is with the Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Dr Reaman is with the Department of Pediatric Hematology-Oncology, Children's National Medical Center, Washington, DC. Dr Pendergrass is with the Department of Pediatric Hematology-Oncology, Children's Hospital and Medical Center, Seattle, WA. Address correspondence to Dr Ross, Children's Cancer Group, P.O. Box 60012, Arcadia, CA 91066-6012, USA. This research was supported in part by the University of Minnesota Children's Cancer Research Fund, NIH training grant T32 09607, and NCI grants CA42479, CA49450, CA58051 from the United States Department of Health and Human Services. Participating Children's Cancer Group investigators, institutions, and grant numbers (Division of Cancer Treatment, National Cancer Institute) are provided in the appendix.     

Noncontraceptive hormone use and risk of breast cancer

All British Columbia (Canada) women under 75 years of age who were diagnosed with breast cancer during 1988–89 were asked to complete a postal questionnaire which included detailed information on menopausal estrogen use. Controls were drawn from the Provincial Voters List, matched by five-year age category to the cases. The present analysis consists of 699 cases and 685 controls who were postmenopausal due to natural causes or to a hysterectomy. There was no overall increase in risk of breast cancer associated with ever-use of unopposed estrogen (odds ratio [OR] = 1.0,95 percent confidence interval [CI] = 0.8–1.3). For estrogen use of 10 years or longer, the relative risk [RR] was 1.6 (CI = 1.1–2.5). The risk estimate for current users was somewhat elevated (OR = 1.4, CI = 1.0–2.0). Compared with women who never used hormone preparations, women who had used estrogen plus progestogen had an RR of 1.2 (CI = 0.6–2.2). Our results suggest that ever-use of estrogen, with or without progestogen, does not appreciably increase the risk of breast cancer. However, long-term and recent use of unopposed estrogen may be associated with a moderately increased risk.Drs Yang and Band, and Mr Gallagher are with the British Columbia Cancer Agency, Vancouver, Britsh Columbia, Canada. Authors are also affiliated with the School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA (Drs Yang, Daling, White, and Weiss), and the Fred Hutchinson Cancer Research Center, Seattle, WA, USA (Drs Daling, White, and Weiss). Address correspondence to Mr Gallagher, Division of Epidemiology, Biometry and Occupational Oncology, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC, Canada, V5Z 4E6. This project is funded partially by Health and Welfare Canada, Grant #6610-1834-55 and by Workers Compensation Board of BC.     

Recent oral contraceptive use and risk of breast cancer (United States)

We examined the association between recent oral contraceptive (OC) use and the risk of breast cancer in data from a large population-based case-control study in the United States. Cases (n=6,751) were women less than 75 years old who had breast cancer identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls (n=9,311) were selected randomly from lists of licensed drivers (if aged under 65 years) and from lists of Medicare beneficiaries (if aged 65 through 74 years). Information on OC use, reproductive experiences, and family and medical history was obtained by telephone interview. After adjustment for parity, age at first delivery, and other risk factors, women who had ever used OCs were at similar risk of breast cancer as never-users (relative risk [RR]=1.1, 95 percent confidence interval [CI]=10–1.2). Total duration of usealso was not related to risk. There was a suggestion that more recent use was associated with an increased risk of breast cancer; use less than two years ago was associated with an RR of 1.3 (CI=0.9–1.9). However, only among women aged 35 to 45 years at diagnosis was the increase in risk among recent users statistically significantly elevated (RR=2.0, CI=1.1–3.9). Use prior to the first pregnancy or among nulliparous women was not associated with increased risk. Among recent users of OCs, the risk associated with use was greatest among non-obese women, e.g., among women with body mass index (kg/m²) less than 20.4, RR=1.7, CI=1.1–2.8. While these results suggest that, in general, breast cancer risk is not increased substantially among women who have used OCs, they also are consistent with a slight increased risk among subgroups of recent users.Authors are with the University of Wisconsin Comprehensive Cancer Center, Madison, WI, USA (Dr Newcomb, Ms Trentham Dietz); NIEHS Epidemiology Branch, Research Triangle Park, NC (Dr Longnecker); Fred Hutchinson Cancer Research Center, Seattle, WA (Dr Surer); Department of Obstetrics and Gynecology, Pritzker School of Medicine, The University of Chicago, Chicago, IL (Dr Mittendorf); Department of Community and Family Medicine, Dartmouth Medical School, Hanover, NH (Dr Baron); Boston University, School of Public Health, Boston, MA (Dr Clapp); Department of Epidemiology and Department of Nutrition, Harvard School of Public Health, and Channing Laboratory, Harvard Medical School and Department of Medicine, Brigham and Women's Hospital, Boston, MA (Dr Willett). Address correspondence to: Dr Polly A. Newcomb, University of Wisconsin-Madison Comprehensive Cancer Center, 1300 University Ave., #4780, Madison, WI 53706, USA. Supported by Public Health Service (National Cancer Institute) grants R01 CA 47147 and R01 CA 47305.     

Recent cohort trends in malignant melanoma by anatomic site in the United States

The incidence of malignant melanoma has been increasing steadily in the United States. The increase may be due to lifestyle changes in subsequent generations or birth cohorts. The nine population-based tumor registries in the Surveillance, Epidemiology, and End Results program (SEER) have been in existence for a sufficient time to begin to investigate cohort trends for the US population. Cases were the 18.787 Caucasians aged 20 to 84 years, who reported to SEER registries with a diagnosis of melanoma in 1974–86. Among men born between 1890 and 1919, each subsequent five-year birth cohort experienced 45 to 57 percent increases in age-adjusted melanoma incidence of the arm and trunk, and 14 to 20 percent increases were experienced across each site (arm, leg, head, and trunk) for the 1920–44 cohorts of men. Among women born between 1890 and 1919, 24 to 29 percent increases were seen for melanoma of the trunk, arms, and legs for each subsequent five-year birth-cohort, followed by six to 29 percent increases in the 1920–44 cohorts. Recent birth cohorts, 1945–64, have shown stabilizing rates, even after an attempt to adjust for the increasing tendency for diagnoses to be made in doctors' offices. Thus, the dramatic birth-cohort effects appear to have ended beginning with those born in 1945. However, melanoma rates will continue to rise until those born after 1945 represent the majority of the population. Furthermore, for the most recent cohorts, the trunk has become the most common site (per square meter of body surface) for men and the second most common site for women. This suggests that some lifestyle change has led to more damaging exposure (e.g., sunburns) of the trunk among recent cohorts than earlier cohorts.Authors are with Fred Hutchinson Cancer Research Center, Seattle, WA, and the Department of Epidemiology at the School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA. Address correspondence to Dr Dennis, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, MP702, Seattle, WA98104, USA. This research was supported by grant CA 34847 from the US National Cancer Institute.     

Life After Cancer Epidemiology (LACE) Study: A cohort of early stage breast cancer survivors (United States)

The Life After Cancer Epidemiology (LACE) Study, a cohort of 2321 early stage breast cancer survivors, was established in 2000 to examine how modifiable behavioral risk factors affect quality of life and long-term survival. Women were recruited primarily from the Kaiser Permanente Northern California Cancer Registry (KPNCAL) and the Utah cancer registry (UCR), United States. Baseline data were collected, on average, at two years post-diagnosis through self-administered questionnaires that included information on demographics, medical history, anthropometry, diet, supplements, physical activity and quality of life. The purpose of this paper is to describe the creation and baseline characteristics of the cohort. Forty-six percent of women to whom questionnaires were mailed agreed to participate. The cohort which is 80% white, was diagnosed predominantly with Stage I and II breast cancer (93%), and will have been followed for 5.6 years post-diagnosis, on average, by the end of 2004. Women reported slightly over four daily servings of fruit and vegetables, well below the suggested 5-A-Day national guidelines. Compared to women free of cancer, physical activity patterns were similar, while weight gain, especially in younger women, was higher than is typical. These data suggest that in the early years post-diagnosis, breast cancer survivors exhibit similar patterns to the general population in many health behaviors.* Address correspondence to: Bette Caan, Dr. PH, Division of Research, Kaiser Permanente Medical Program, 2000 Broadway, Oakland, CA 94612, USA. Ph.: +1-510-891-3719; Fax: +1-510-891-3761; E-mail: Bjc@dor.kaiser.org