Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3).

BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.

BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3).

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

Late adulthood mortality among African-American and white American people with Type 1 diabetes according to age at diabetes diagnosis.

AIMS: To estimate the overall and cause-specific mortality in a population of African-Americans and white Americans with a low socio-economic status who had young-onset insulin-treated diabetes and had survived beyond the age of 40 years, and to examine whether any excess risk varied according to age at diabetes onset. METHODS: Using the Southern Community Cohort Study, we conducted a mortality follow-up of a cohort of mostly low-income participants aged 40-79 years (mean 50 years) at cohort entry with insulin-treated diabetes diagnosed before age 30 years (n=475) and without diabetes (n=62 266). Childhood onset was defined as diabetes diagnosed before age 20 years (n=162), while young-adulthood onset was defined as diabetes diagnosed between ages 20 and 29 years (n=313). Cause-specific mortality was based on both underlying and contributing causes of death, obtained from death certificates. Multivariable Cox analysis was performed. RESULTS: During follow-up (mean 9.5 years), 38.7% of those with and 12.9% of those without diabetes died. Compared with those without diabetes, increases in mortality rate were generally similar among those with childhood- and young-adulthood-onset diabetes for deaths from: all causes (childhood: hazard ratio 4.3, CI 3.3-5.5; young adulthood: hazard ratio 4.9, CI 4.0-5.8); ischaemic heart disease (childhood: hazard ratio 5.7, CI 3.5-9.4; young adulthood: hazard ratio 7.9, CI 5.6-11.0); heart failure (childhood: hazard ratio 7.3, CI 4.2-12.7; young adulthood: hazard ratio 5.4, CI 3.3-8.9); sepsis (childhood: hazard ratio 10.3, CI 6.1-17.3; young adulthood: hazard ratio 8.8, CI 5.7-13.5); renal failure (childhood: hazard ratio 15.1, CI 8.6-26.5; young adulthood: hazard ratio 18.2, CI 12.3-27.1); respiratory disorders (childhood: hazard ratio 3.9, CI 2.3-6.7; young adulthood: hazard ratio 5.3, CI 3.7-7.7); suicide/homicide/accidents (childhood: hazard ratio 2.3, CI 0.72-7.0; young adulthood: hazard ratio 5.8, CI 3.4-10.2); and cancer (childhood: hazard ratio 2.1, CI 0.98-4.4; young adulthood: hazard ratio 1.2, CI 0.55-2.5). CONCLUSIONS: We observed high excess long-term mortality for all-cause, renal failure, ischemic heart disease and heart failure mortality in African-American and white American people with early-onset insulin-treated diabetes.

Association of oral microbiome with type 2 diabetes risk.

BACKGROUND AND OBJECTIVE: The oral microbiome may help to maintain systemic health, including how it affects blood glucose levels; however, direct evidence linking the oral microbiome with diabetes is lacking. MATERIAL AND METHODS: We compared the oral microbiome profiles of 98 participants with incident diabetes, 99 obese non-diabetics and 97 normal weight non-diabetics, via deep sequencing of the 16S rRNA gene. RESULTS: We found that the phylum Actinobacteria was present significantly less abundant among patients with diabetes than among the controls (p = 3.9 × 10-3 ); the odds ratio (OR) and 95% confidence interval (CI) was 0.27 (0.11-0.66) for those individuals who had relative abundance higher than the median value. Within this phylum, five families and seven genera were observed, and most of them were less abundant among patients with diabetes. Notably, genera Actinomyces and Atopobium were associated with 66% and 72% decreased risk of diabetes with p-values of 8.9 × 10-3 and 7.4 × 10-3 , respectively. Stratified analyses by race showed that most taxa in this phylum were associated with diabetes in both black and white participants. This phylum was also less abundant among non-diabetic obese subjects compared to normal weight individuals, particularly genera Mobiluncus, Corynebacterium and Bifidobacterium, which showed p < 0.05. CONCLUSION: Our study revealed that multiple bacteria taxa in the phylum Actinobacteria are associated with the risk of type 2 diabetes. Some are also associated with the prevalence of obesity, suggesting that the oral microbiome may play an important role in diabetes etiology.

Oral health and risk of colorectal cancer: results from three cohort studies and a meta-analysis.

BACKGROUND: While studies have shown that poor oral health status may increase the risk of cancer, evidence of a specific association with the risk of colorectal cancer (CRC) is inconclusive. We evaluated the association between oral health and CRC risk using data from three large cohorts: the Shanghai Men's Health Study (SMHS), the Shanghai Women's Health Study (SWHS), and the Southern Community Cohort Study (SCCS), and carried out a meta-analysis of results from other relevant published studies. PATIENTS AND METHODS: This study applied a nested case-control study design and included 825 cases/3298 controls from the SMHS/SWHS and 238 cases/2258 controls from the SCCS. The association between oral health status (i.e. tooth loss/tooth decay) and CRC risk was assessed using conditional logistic regression models. A meta-analysis was carried out based on results from the present study and three published studies. RESULTS: We found that tooth loss was not associated with increased risk of CRC. ORs and respective 95% CIs associated with loss of 1-5, 6-10, and >10 teeth compared with those with full teeth are 0.87 (0.69-1.10), 0.93 (0.70-1.24), and 0.85 (0.66-1.11) among SMHS/SWHS participants; and 1.13 (0.72-1.79), 0.87 (0.52-1.43), and 1.00 (0.63-1.58) for those with loss of 1-4, 5-10, and >10 teeth among SCCS participants. Data regarding tooth decay were available in the SCCS, but were not associated with CRC risk. Meta-analysis confirmed the null association between tooth loss/periodontal disease and CRC risk (OR 1.05, 95% CI 0.86-1.29). CONCLUSION: In this analysis of three cohorts and a meta-analysis, we found no evidence supporting an association between oral health and CRC risk.

Higher protein intake is associated with increased risk for incident end-stage renal disease among blacks with diabetes in the Southern Community Cohort Study.

BACKGROUND AND AIMS: Diabetes, a risk factor for end-stage renal disease (ESRD), is associated with impaired protein metabolism. We investigated whether protein intake is associated with ESRD and whether the risk is higher among blacks with diabetes. METHODS AND RESULTS: We conducted a nested case-control study of ESRD within the Southern Community Cohort Study, a prospective study of low-income blacks and whites in the southeastern US (2002-2009). Through 2012, 1057 incident ESRD cases were identified by linkage with the United States Renal Data System and matched to 3198 controls by age, sex, and race. Dietary intakes were assessed from a validated food frequency questionnaire at baseline. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models that included matching variables, BMI, education, income, hypertension, total energy intake, and percent energy from saturated and polyunsaturated fatty acids. Mean (±SD) daily energy intake from protein was higher among ESRD cases than controls (15.7 ± 3.3 vs. 15.1 ± 3.1%, P < 0.0001). For a 1% increase in percent energy intake from protein, the adjusted ORs (95% CIs) for ESRD were 1.06 (1.02-1.10) for blacks with diabetes, 1.02 (0.98-1.06) for blacks without diabetes, 0.99 (0.90-1.09) for whites with diabetes and 0.94 (0.84-1.06) for whites without diabetes. Protein intake in g/kg/day was also associated with ESRD (4th vs. 1st quartile OR = 1.76; 95% CI: 1.17-2.65). CONCLUSION: Our results raise the possibility that among blacks with diabetes, increased dietary protein is associated with increased incidence of ESRD. Studies on how protein intake and metabolism affect ESRD are needed.

Cause-specific mortality by race in low-income Black and White people with Type 2 diabetes.

AIM: To investigate, with extended follow-up, cause-specific mortality among low-income Black and White Americans with Type 2 diabetes who have similar socio-economic status. METHODS: Black and White Americans aged 40-79 years with Type 2 diabetes (n = 12 498) were recruited from community health centres as part of the Southern Community Cohort Study. Multivariable Cox analysis was used to estimate mortality hazard ratios and 95% CIs for subsequent cause-specific mortality, based on both underlying and contributing causes of death. RESULTS: During the follow-up (median 5.9 years), 13.3% of the study population died. The leading causes of death in each race were ischaemic heart disease, respiratory disorders, cancer, renal failure and heart failure; however, Blacks were at a lower risk of dying from ischaemic heart disease (hazard ratio 0.70, 95% CI 0.54-0.91) or respiratory disorders (hazard ratio 0.70, 0.53-0.92) than Whites but had higher or similar mortality attributable to renal failure (hazard ratio 1.57, 95% CI 1.02-2.40), heart failure (hazard ratio 1.47, 95% CI 0.98-2.19) and cancer (hazard ratio 0.87, 95% CI 0.62-1.22). Risk factors for each cause of death were generally similar in each race. CONCLUSIONS: These findings suggest that the leading causes of death and their risk factors are largely similar among Black and White Americans with diabetes. For the two leading causes of death in each race, however, ischaemic heart disease and respiratory disorders, the magnitude of risk is lower among Black Americans and contributes to their higher survival rates.

Fish, omega-3 long-chain fatty acids, and all-cause mortality in a low-income US population: Results from the Southern Community Cohort Study.

BACKGROUND: We examined associations between fish and n-3 LCFA and mortality in a prospective study with a large proportion of blacks with low socio-economic status. METHODS AND RESULTS: We observed 6914 deaths among 77,604 participants with dietary data (follow-up time 5.5 years). Of these, 77,100 participants had available time-to-event data. We investigated associations between mortality with fish and n-3 LCFA intake, adjusting for age, race, sex, kcal/day, body mass index (BMI), smoking, alcohol consumption, physical activity, income, education, chronic disease, insurance coverage, and meat intake. Intakes of fried fish, baked/grilled fish and total fish, but not tuna, were associated with lower mortality among all participants. Analysis of trends in overall mortality by quintiles of intake showed that intakes of fried fish, baked/grilled fish and total fish, but not tuna, were associated with lower risk of total mortality among all participants. When participants with chronic disease were excluded, the observed association remained only between intakes of baked/grilled fish, while fried fish was associated with lower risk of mortality in participants with prevalent chronic disease. The association between n-3 LCFA intake and lower risk of mortality was significant among those with diabetes at baseline. There was an inverse association of mortality with fried fish intake in men, but not women. Total fish and baked/grilled fish intakes were associated with lower mortality among blacks while fried fish intake was associated with lower mortality among whites. Effect modifications were not statistically significant. CONCLUSION: Our findings suggest a modest benefit of fish consumption on mortality.

Intake of polyunsaturated fat in relation to mortality among statin users and non-users in the Southern Community Cohort Study.

BACKGROUND AND AIMS: Consumption of polyunsaturated fatty acids (PUFA), especially the n3-series, may protect against cardiovascular disease (CVD), but recent randomized studies have failed to demonstrate these benefits. One of the prevailing hypotheses is that PUFA intake may not confer benefits beyond those provided by statins, but studies comparing statin users to non-users with regard to effects of PUFA are lacking. METHODS AND RESULTS: Black and white men and women (n = 69,559) in the Southern Community Cohort Study were studied. Cox regression models adjusting for age, sex, race, BMI, recruitment site, education, income, smoking, diabetes, and dietary variables were used. RESULTS: At baseline the mean ± SD age was 52 ± 9 years, 60% of participants were women, 54% had hypertension and 16% used statins. We observed modest inverse associations between n3-PUFA and n6-PUFA intake with mortality among non-statin users but not among statin users. In adjusted analyses, the HRs (95% CIs) for all-cause mortality (6,396 deaths over a median of 6.4 years) comparing the highest to the lowest quintile were 0.90 (0.82-1.00) for n3-PUFA and 0.80 (0.70-0.92) for n6-PUFA among non-statin users, whereas they were 1.06 (0.87-1.28) and 0.96 (0.78-1.19) for n3-PUFA and n6-PUFA, respectively, among statin users. CONCLUSIONS: Our results suggest potential benefits of PUFA consumption on mortality which are only apparent in the absence of statin therapy. It seems prudent to consider the potential benefit of PUFA consumption in the primary prevention of CVD among patients who are not candidates for statin therapy but are at increased risk for CVD and mortality.

Cancer mortality in U.S. counties with petroleum industries.

A survey of cancer mortality from 1950 to 1969 was conducted in U.S. counties where the petroleum industry is most heavily concentrated. Male residents of these counties experienced significantly higher rates for cancers of the lung, the nasal cavity and sinuses, and the skin (including malignant melanoma) compared to male residents of counties with similar demographic characteristics. Further study is needed to determine whether these patterns result from exposure to chemical carcinogens, including polycyclic hydrocarbons, involved in the manufacturing of petroleum.

The impact of sociodemographic factors and PSA screening among low-income Black and White men: data from the Southern Community Cohort Study.

BACKGROUND: Variation in PSA screening is a potential source of disparity in prostate cancer survival, particularly among underserved populations. We sought to examine the impact of race and socioeconomic status (SES) on receipt of PSA testing among low-income men. METHODS: Black (n=22 167) and White (n=9588) men aged ⩾40 years completed a baseline questionnaire from 2002 to 2009 as part of the Southern Community Cohort Study. Men reported whether they had ever received PSA testing and had testing within the prior 12 months. To evaluate the associations between SES, race and receipt of PSA testing, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from the multivariable logistic models where age, household income, insurance status, marital status, body mass index and educational level were adjusted. RESULTS: Black men were younger, had a lower income, less attained education and were more likely to be unmarried and uninsured (all P<0.001). Percentages of men having ever received PSA testing rose from <40% under the age of 45 years to ~90% above the age of 65 years, with Whites >50 more likely than Blacks to have received testing. Lower SES was significantly associated with less receipt of PSA testing in both groups. After adjustment for SES, White men had significantly lower odds of PSA testing (OR 0.81; 95% CI: 0.76-0.87). CONCLUSIONS: Greater PSA testing among White than Black men over the age of 50 years in this low-income population appears to be mainly a consequence of SES. Strategies for PSA screening may benefit from tailoring to the social circumstances of the men being screened.

Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders.

INTRODUCTION: Although it has been hypothesised that metal welding and flame cutting are associated with an increased risk for Parkinson's disease due to manganese released in the welding fume, few rigorous cohort studies have evaluated this risk. METHODS: The authors examined the relation between employment as a welder and all basal ganglia and movement disorders (ICD-10, G20-26) in Sweden using nationwide and population based registers. All men recorded as welders or flame cutters (n = 49,488) in the 1960 or 1970 Swedish National Census were identified and their rates of specific basal ganglia and movement disorders between 1964 and 2003 were compared with those in an age and geographical area matched general population comparison cohort of gainfully employed men (n = 489,572). RESULTS: The overall rate for basal ganglia and movement disorders combined was similar for the welders and flame cutters compared with the general population (adjusted rate ratio (aRR) = 0.91 (95% CI 0.81 to 1.01). Similarly, the rate ratio for PD was 0.89 (95% CI 0.79 to 0.99). Adjusted rate ratios for other individual basal ganglia and movement disorders were also not significantly increased or decreased. Further analyses of Parkinson's disease by attained age, time period of follow up, geographical area of residency, and educational level revealed no significant differences between the welders and the general population. Rates for Parkinson's disease among welders in shipyards, where exposures to welding fumes are higher, were also similar to the general population (aRR = 0.95; 95% CI 0.70 to 1.28). CONCLUSION: This nationwide record linkage study offers no support for a relation between welding and Parkinson's disease or any other specific basal ganglia and movement disorders.

Assessment of lung cancer risk factors by histologic category.

The patterns of risk by histologic type of lung cancer were analyzed with the use of data from a large hospital-based case-control study (7,804 cases and 15,207 controls) of lung cancer performed in Western Europe. Relative risks (RR) increased with duration of cigarette use for all histologic types, although the gradients of risk were greater for Kreyberg I cell types, particularly squamous cell carcinoma (SCC), than for adenocarcinoma (AC). Risks also declined more sharply with years since cessation of smoking for all Kreyberg I cell types, in particular for SCC, rather than for AC. After adjustment for duration of use, the RR associated with number of cigarettes smoked per day, frequency and depth of inhalation, and fraction of cigarette consumed were not consistently different by cell type, suggesting that intensity-related measures of cigarette exposure have less effect on cell type than duration-related factors. Among those who never smoked there were marked cell type differences by sex, with a greater proportion of AC compared to SCC for females (45 vs. 25%) than for males (35 vs. 33%). Review of limited work histories indicated that occupational associations also were more strongly related to Kreyberg I than to Kreyberg II tumors.

Geographic patterns of renal cancer in the United States.

Mapping of the geographic distribution of renal cancer mortality for groupings of U.S. counties revealed clustering of elevated rates among white males and females in the upper north-central part of the country. Throughout the United States, mortality increased with urbanization for males only, whereas rates for both sexes showed positive correlations with socioeconomic status. The major correlate of the cancer rates was ethnicity. Mortality was elevated in counties with high percentages of residents of German, Scandinavian, and especially Russian descent. Ethnic susceptibility appears to account, at least partly, for the regional clustering of kidney cancer and may provide leads to environmental determinants.

Is Hodgkin's disease infectious? Discussion of an epidemiologic method used to impute that it is.

A method proposed by MacMahon for the differentiation between familial and environmental causes for disease has recently been applied to demonstrate an environmental etiology for Hodgkin's disease. It is shown that the method, which depends on the comparison of time-of-onset differences with age-at-onset differences for familial pairs with disease, is biased toward results suggestive of an environmental etiology when applied to data of the kind typically analyzed--data restricted to instances in which both members of a familial pair develop disease in a specified, limited time interval. Other features of such data are discussed.

Geographic patterns of bladder cancer in the United States.

Age-adjusted rates of mortality during 1950-69 from bladder cancer were correlated with demographic and industrial indexes for the 3,056 counties of the contiguous United States. Rates among whites and nonwhites of both sexes rose sharply with urbanization. A small but positive socioeconomic gradient was observed, and mortality was slightly higher among males in counties with high percentages of British and German residents. Even after controlling for demographic variables, the Northeastern excess of bladder cancer among whites was sizable, whereas the regional differences among nonwhites were small. The high rates in the Northeast were seen in both sexes and in rural as well as urban areas, with mortality in small counties in upstate New York and New England equaling or exceeding those in large metropolitan centers elsewhere in the country. Outside the Northeast, high rates were generally limited to urban areas, but clusters of elevated mortality occurred among white males along the Illinois-Wisconsin border, in parts of lower Michigan, and in southern Louisiana. Industrial factors may explain at least part of the geographic clustering, inasmuch as rates among males were significantly higher in U.S. counties where the chemical industry is heavily concentrated. Increases were also associated with the printing industry, but correlations with 16 other major manufacturing industries were near or below expected levels.

Cigarette smoking, alcohol, and nasopharyngeal carcinoma: a case-control study among U.S. whites.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a relatively uncommon cancer in the United States. Its etiology among White Americans is not well known, but cigarette smoking has been implicated in some epidemiologic studies. PURPOSE: The purpose of this study was to investigate the roles of cigarette use and alcohol consumption as risk factors for NPC in the United States. METHODS: We conducted a case-control study using data from the National Mortality Followback Survey based on information from death certificates. In this study, we compared use of cigarettes and alcohol by 204 White American men and women who died of NPC with that by 408 who died of causes unrelated to cigarette smoking and alcohol use. RESULTS: Risk of NPC increased in proportion to the amount and duration of smoking (with a more than threefold increase among persons smoking heavily) and declined following cessation of smoking. After controlling for smoking, we found an 80% excess risk of NPC among persons whose intake of alcohol was heavy. CONCLUSION: Use of cigarettes and consumption of alcohol were found to be statistically significant risk factors for NPC. The findings are among the strongest to date indicating that use of cigarettes and perhaps alcohol may contribute to the etiology of these relatively rare cancers among Whites in the United States.

Declining breast cancer mortality among young American women.

Changes in age-specific breast cancer mortality rates among white females in the United States during 1950-80 were shown to be correlated with changes in patterns of childbearing in early adulthood. However, for the most recent 5-year period among women below age 40 years, small declines in breast cancer mortality were observed in the late 1970's, despite a predicted increase following delays in childbearing that began in the 1960's and despite evidence of a rising incidence of the cancer. Although correlation analyses have inherent limitations, the findings raise the possibility that recent changes in the detection and management of breast cancer have contributed to a lowered mortality from this cancer among young American women.