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Background: The role of estrogen metabolism in determining breast cancer risk and differences in breast cancer rates between high-incidence and low-incidence nations is poorly understood.Methods: We measured urinary concentrations of estradiol and estrone (parent estrogens) and 13 estrogen metabolites formed by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring in a nested case-control study of 399 postmenopausal invasive breast cancer case participants and 399 matched control participants from the population-based Shanghai Women's Health Study cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by quartiles of metabolic pathway groups, pathway ratios, and individual estrogens/estrogen metabolites were estimated by multivariable conditional logistic regression. Urinary estrogen/estrogen metabolite measures were compared with those of postmenopausal non-hormone-using Asian Americans, a population with three-fold higher breast cancer incidence rates. All statistical tests were two-sided.Results: Urinary concentrations of parent estrogens were strongly associated with breast cancer risk (ORQ4vsQ1 = 1.94, 95% CI = 1.21 to 3.12, Ptrend = .01). Of the pathway ratios, the 2-pathway:total estrogens/estrogen metabolites and 2-pathway:parent estrogens were inversely associated with risk (ORQ4vsQ1 = 0.57, 95% CI = 0.35 to 0.91, Ptrend = .03, and ORQ4vsQ1 = 0.61, 95% CI = 0.37 to 0.99, Ptrend = .04, respectively). After adjusting for parent estrogens, these associations remained clearly inverse but lost statistical significance (ORQ4vsQ1 = 0.65, 95% CI = 0.39 to 1.06, Ptrend = .12 and ORQ4vsQ1 = 0.76, 95% CI = 0.44 to 1.32, Ptrend = .28). The urinary concentration of all estrogens/estrogen metabolites combined in Asian American women was triple that in Shanghai women.Conclusions: Lower urinary parent estrogen concentrations and more extensive 2-hydroxylation were each associated with reduced postmenopausal breast cancer risk in a low-risk nation. Markedly higher total estrogen/estrogen metabolite concentrations in postmenopausal United States women (Asian Americans) than in Shanghai women may partly explain higher breast cancer rates in the United States. [ABSTRACT FROM AUTHOR]

Background Recently, several genome-wide association studies have identified various genetic susceptibility loci for breast cancer. Relatively little is known about the possible interactions between these loci and the established risk factors for breast cancer. Methods To assess interactions between single-nucleotide polymorphisms (SNPs) and established risk factors, we prospectively collected DNA samples and questionnaire data from 8576 breast cancer case subjects and 11 892 control subjects nested within the National Cancer Institute’s Breast and Prostate Cancer Cohort Consortium (BPC3). We genotyped 17 germline SNPs (FGFR2-rs2981582, FGFR2-rs3750817, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, CASP8-rs1045485, LSP1-rs3817198, COL1A1-rs2075555, COX11-rs6504950, RNF146-rs2180341, 6q25-rs2046210, SLC4A7-rs4973768, NOTCH2-rs11249433, 5p12-rs4415084, 5p12-rs10941679, RAD51L1-rs999737), and odds ratios were estimated by logistic regression to confirm previously reported associations with breast cancer risk. We performed likelihood ratio test to assess interactions between 17 SNPs and nine established risk factors (age at menarche, parity, age at menopause, use of hormone replacement therapy, family history, height, body mass index, smoking status, and alcohol consumption), and a correction for multiple testing of 153 tests (adjusted P value threshold = .05/153 = 3 × 10−4) was done. Case–case comparisons were performed for possible differential associations of polymorphisms by subgroups of tumor stage, estrogen and progesterone receptor status, and age at diagnosis. All statistical tests were two-sided. Results We confirmed the association of 14 SNPs with breast cancer risk (Ptrend = 2.57 × 10−3 –3.96 × 10−19). Three SNPs (LSP1-rs3817198, COL1A1-rs2075555, and RNF146-rs2180341) did not show association with breast cancer risk. After accounting for multiple testing, no statistically significant interactions were detected between the 17 SNPs and the nine risk factors. We also confirmed that SNPs in FGFR2 and TNRC9 were associated with greater risk of estrogen receptor–positive than estrogen receptor–negative breast cancer (Pheterogeneity = .0016 for FGFR2-rs2981582 and Pheterogeneity = .0053 for TNRC9-rs3803662). SNP 5p12-rs10941679 was statistically significantly associated with greater risk of progesterone receptor–positive than progesterone receptor–negative breast cancer (Pheterogeneity = .0028). Conclusion This study does not support the hypothesis that known common breast cancer susceptibility loci strongly modify the associations between established risk factors and breast cancer. [ABSTRACT FROM PUBLISHER]

Background: Excess mortality from lymphohematopoietic malignancies, in particular myeloid leukemia, and brain cancer has been found in surveys of anatomists, pathologists, and funeral industry workers, all of whom may have worked with formaldehyde. We investigated the relation of mortality to work practices and formaldehyde exposure levels among these professionals to address cancer risk in the funeral industry. [ABSTRACT FROM PUBLISHER]

Background: Breast cancer incidence has been rising since at least 1935-1939, but recent US data reveal a statistically significant decline in breast cancer incidence in 2003 that persisted through 2004. Identifying the specific contributions of the potential causes of this long-term increase and the recent decrease in incidence has been challenging. Marked changes in rates of mammography screening and use of menopausal hormone therapy since 1980 have added further complexity. We examined the potential association between menopausal hormone therapy use and recent changes in breast cancer incidence. Methods: Using tumor registry, clinical, pathology, and pharmacy data from Kaiser Permanente Northwest, a large prepaid US health plan, we compared age-specific and age-adjusted breast cancer incidence rates (2-year moving averages) with use of screening mammography and dispensed menopausal hormone therapy prescriptions between 1980 and 2006. Temporal changes in incidence rates were assessed via joinpoint regression. Results: A total of 7386 incident invasive breast cancers were diagnosed in plan members from 1980 through 2006. Overall age-adjusted breast cancer incidence rates per 100,000 women rose 25% from the early 1980s (105.6) to 1992-1993 (131.7) and an additional 15% through 2000-2001 (151.3), then dropped by 18% to 2003-2004 (123.6) and edged up slightly in 2005-2006 (126.2). These patterns were largely restricted to women aged 45 years or older and to estrogen receptor-positive (ER+) breast cancers. Incidence rates of ER-negative tumors experienced neither of the rises seen for ER+ tumors but also fell precipitously from 2003 through 2006. Rates of mammography screening sharply increased from 1980 to 1993 but then leveled off, and 75%-79% of women aged 45 years or older received a mammogram at least once every 2 years from 1993 through 2006. Menopausal hormone therapy dispensings, particularly of estrogen-plus-progestin formulations, increased from 1988 to 2002 but then dropped by approximately 75% after 2002. Conclusions: From 1980 through 2006, quantitative and qualitative trends in breast cancer incidence rates, particularly for ER+ tumors, parallel major changes in patterns of mammography screening and use of menopausal hormone therapy. [ABSTRACT FROM AUTHOR]

Investigates the association between prenatal diethylstilbestrol (DES) exposure and testicular cancer risk in the United States. Use of relative rate to assess the strength of the association between prenatal DES exposure and cancer risk;

Presents a study on breast cancer mortality among women who were diagnosed with axillary lymph node-negative and node-positive breast cancer according to the currency of estrogen use at diagnosis. Use of hormone replacement theraphy; Methods used in the study.

Assesses the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin. Reproducibility of laboratory analysis; Blood collection; Case patients and control subjects.

Examines breast cancer incidence rates among Asian-American women. Roles of adult height and weight change in breast cancer etiology; Assessment of exposure; Relative risk estimated by the odds ratio; Importance of adiposity at different periods of adult life.

Evaluates whether differences in use of alcohol and tobacco can account for the high incidence of squamous cell esophageal cancer among blacks in the United States. Population-based, case-control study with in-person interviews; Comparison to rates among whites; Interaction of race and the smoking/drinking variable.

: 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. : Our objective was to quantify breast cancer risks associated with the various migration patterns of Asian-American women. : 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%). : 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. : 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. : 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. [J Natl Cancer Inst 85:1819–1827, 1993] [ABSTRACT FROM PUBLISHER]

Background: Experimental studies have provided strong evidence that human papillomavirus (HPV) is the long-sought venereal cause of cervical neoplasia, but the epidemiologic evidence has been inconsistent.Purpose: Given improvements in HPV testing that have revealed a strong link between sexual activity history and cervical HPV infection, we conducted a large case-control study of HPV and cervical intraepithelial neoplasia (CIN) to evaluate whether sexual behavior and the other established risk factors for CIN influence risk primarily via HPV infection.Methods: We studied 500 women with CIN and 500 control subjects receiving cytologic screening at Kaiser Permanente, a large prepaid health plan, in Portland, Ore. The established epidemiologic risk factors for CIN were assessed by telephone interview. We performed HPV testing of cervicovaginal lavage specimens by gene amplification using polymerase chain reaction with a consensus primer to target the L1 gene region of HPV. Unconditional logistic regression analysis was used to estimate relative risk of CIN and to adjust the epidemiologic associations for HPV test results to demonstrate whether the associations were mediated by HPV.Results: The case subjects demonstrated the typical epidemiologic profile of CIN: They had more sex partners, more cigarette smoking, earlier ages at first sexual intercourse, and lower socioeconomic status. Statistical adjustment for HPV infection substantially reduced the size of each of these case-control differences. Seventy-six percent of cases could be attributed to HPV infection; the results of cytologic review suggested that the true percentage was even higher. Once HPV infection was taken into account, an association of parity with risk of CIN was observed in both HPV-negative and HPV-positive women.Conclusion: The data show that the great majority of all grades of CIN can be attributed to HPV infection, particularly with the cancer-associated types of HPV.Implications: In light of this conclusion, the investigation of the natural history of HPV has preventive as well as etiologic importance. [ABSTRACT FROM AUTHOR]

In a case-control study, we tested the hypothesis that the genetically determined ability to metabolize debrisoquine is related to risk of lung cancer. Overall, individuals who were extensive metabolizers of debrisoquine were at significantly greater risk of lung cancer than those who were poor or intermediate metabolizers (odds ratio = 6.1; 95% confidence interval = 2.2–17.1). In this study, case patients had lung cancer, and control subjects had either chronic obstructive c pulmonary disease or cancers other than lung cancer. Results were adjusted for age, race, asbestos exposure, and smoking. Both black and white individuals who were extensive metab-olizers of debrisoquine were at significantly increased risk after similar adjustment (for blacks, odds ratio =4.5, 95% c confidence interval = 1.1–18.1; for whites, odds ratio =10.2, 95% confidence interval = 2.0–51.4). Significantly increased risk of lung cancer was also present for individuals who were extensive metabolizers when subjects with chronic obstruc- tive pulmonary disease or other cancers were considered separately. These data confirm that the ability to metabolize debrisoquine is a major determinant of susceptibility to lung cancer. Evaluation of the marker in other case-control I settings, further exploration of racial differences, and the prospective evaluation of this marker in subgroups at high risk of lung cancer are areas worthy of further study. [J Natl Cancer Inst 82: 1264–1272, 1990] [ABSTRACT FROM PUBLISHER]

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. [J Natl Cancer Inst 82:693–696,1990] [ABSTRACT FROM PUBLISHER]

We examined the relationship between occupation and bladder cancer risk using data obtained from interviews conducted with 2,100 white males with bladder cancer and 3,874 population controls during the National Bladder Cancer Study, a population-based, case-control study conducted in 10 areas of the United States. The strongest evidence of increased risk among white men was observed for painters, truck drivers, and drill press operatives. For painters, the overall relative risk was 1.5 [95% confidence intervals (CI) = 1.2–2.0]. Among painters who started working prior to 1930, a significant trend in risk with increasing duration of employment as a painter was apparent; the relative risk for such painters employed 10 or more years was 3.0. For truck drivers and drill press operatives, overall risks were 1.3 (CI = 1.1–1.4) and 1.4 (CI = 0.9–2.1), respectively. We observed a significant, positive trend in risk with increasing duration of employment in each of these occupations, with relative risks peaking at approximately two for long-term workers. Excess risks were also observed for workers in several other occupations. In all, we estimate that 21%–25% of bladder cancer diagnosed among white men in the United States is attributable to occupational exposures. [J Natl Cancer Inst 81:1472–1480, 1989] [ABSTRACT FROM PUBLISHER]

Occupational risks of bladder cancer among nonwhite men were assessed based on interviews with 126 cases and 383 controls conducted during the National Bladder Cancer Study, a population-based, case-control study conducted in 10 areas of the United States. Our findings indicated that nonwhite men who were ever employed as auto workers have an elevated risk of bladder cancer (relative risk (RR) =2.3; 95% confidence intervals (CI) = 0.8–6.4) with a significant positive trend in RR with increasing duration of employment (=.017) and with the RR rising to 4.7 for those employed at least 10 years. Dry cleaners, ironers, and pressers also experienced increased bladder cancer risk (RR=2.8, CI = 1.1–7.4). Nonsignificant excesses of similar magnitude to those seen among white men were found for nonwhite men employed in several other occupations. Overall, our findings suggest that the risk of occupational bladder cancer among white and nonwhite men is similar. When inconsistencies between whites and nonwhites did occur, they appeared either due to chance or possibly racial differences in exposure among men within the same industry and occupation. In all, we estimate that the population attributable risk for occupation among nonwhite U.S. men is 27% (CI = 9% to 56%), which is slightly higher than the estimate of 21% to 25% previously reported for white U.S. men, although this difference was not statistically significant. [J Natl Cancer Inst 81: 1480–1483, 1989] [ABSTRACT FROM PUBLISHER]

Details a case-control study which assessed the role of diet and nutrition as risk factors for pancreatic cancer. Incidence of pancreatic cancer in the United States; Subjects and methods; Results and discussion.

Editorial. Comments on the mechanisms of breast cancer prevention. Evidence of the growth promoting action of estrogen; Investigation on the prenatal determinants of pregnancy outcome; Association of breast cancer rate with increased maternal blood pressure, maternal floor infarction of the placenta and small placental weight and diameter.

The article discusses research on opportunities in cancer etiology and prevention. Topics discussed include the advantage of mapping cancer susceptibility, measurement of metabolites, the lack of a reliable estimate of how many small molecules there are for metabolomics, and the causes of a substantial proportion of the overall cancer burden in the population.

Editorial. Discusses the public health dilemmas on dioxins. Result of a comprehensive review conducted by a working group at the International Agency for Research on Cancer in 1997 about the cohorts; Importance of updating the cohort's experience; Patterns of cancer in those exposed to dioxin as a result of the Seveso accident.

Looks at the relationship between farming and prostate cancer incidence in African-Americans in the Southeastern United States. Occupational groups with excess risk for developing prostate cancer; Proportion of mortality in the southeast and other states combined; Limitations of the study.

A response to a letter to the editor is presented about the article "Cancer Incidence, 1980-2006: Combined Roles of Menopausal Hormone Therapy, Screening Mammography, and Estrogen Receptor Status," by A.G. Glass, J.V. Lacey, J.D. Carreon and R.N. Hoover.