Birth Weight and Risk of Childhood Acute Lymphoblastic Leukemia in Arizona, Illinois, and Kentucky.

OBJECTIVE: To confirm the previously reported increased risk of leukemia among macrosomic children (those with birth weight >4 kg). METHODS: Birth certificates of Arizona, Illinois, and Kentucky children diagnosed as having acute lymphoblastic leukemia (ALL) before age 5 years were matched with birth certificates from leukemia-free children of the same sex, race, and ethnicity who were born in the same county on or about the same day. Odds ratios (ORs) for ALL among children of low (<2.5 kg) or high (>4 kg) birth weight were calculated by conditional logistic regression. RESULTS: Children with high birth weight had an elevated risk of ALL in the first 5 years of life (OR 1.28, 95% confidence interval [CI] 1.01-1.61). The excess risk was confined to non-Hispanic whites (OR 1.77, 95% CI 1.27-2.48), both boys (OR 1.57, 95% CI 1.01-2.45) and girls (OR 2.10, 95% CI 1.26-3.52). CONCLUSIONS: This study confirms the association between high birth weight and ALL previously reported by other studies in children of European ancestry. The literature on maternal risk factors for both macrosomia and ALL is reviewed, with maternal overnutrition emerging as a plausible risk factor for both outcomes.

Inverse Correlation of Lymphoid Leukemia Incidence and Anemia Prevalence among Preschool Children.

OBJECTIVE: The relation between the prevalence of anemia and incidence of childhood acute lymphoblastic leukemia was explored using international cross-sectional data as well as US time-series data. METHODS: Lymphoid leukemia incidence rates for various countries from the International Agency for Research on Cancer were regressed on anemia prevalence rates from the World Health Organization in a cross-sectional analysis. Four decades of acute lymphoblastic leukemia incidence (from the Surveillance, Epidemiology, and End Results Program cancer registries) and anemia prevalence (from the National Health and Nutrition Examination Survey) also were examined in a time-series analysis. RESULTS: There was a statistically significant inverse correlation between leukemia incidence and anemia prevalence in 53 countries, with leukemia incidence being highest in those countries where anemia prevalence was lowest. Examination of US leukemia incidence and anemia prevalence trends from 1973 through 2012 revealed similarly contrasting trends, with leukemia incidence increasing while anemia prevalence was decreasing. White children had half as much anemia but twice as much leukemia as black children. CONCLUSIONS: It is postulated that the iron-depleted state may be unfavorable to leukemogenesis, perhaps because lymphopoiesis is suppressed when erythropoiesis is stimulated. Conversely, the iron-replete state may be more favorable to leukemogenesis.

Sleep-disordered breathing is associated with higher carboxymethyllysine level in elderly women but not elderly men in the cardiovascular health study.

CONTEXT: Carboxymethyl-lysine (CML) results from oxidative stress and has been linked to cardiovascular disease. OBJECTIVE: The objective of this study is to investigate the association between sleep-disordered breathing (SDB) - a source of oxidative stress - and CML. MATERIALS AND METHODS: About 1002 participants in the Cardiovascular Health Study (CHS) were studied. RESULTS: Women with SDB had significantly higher CML concentration compared with those without SDB (OR = 1.63, 95%CI = 1.03-2.58, p = 0.04). The association was not significant among men. DISCUSSION: SDB was associated with CML concentration among elderly women but not men in the Cardiovascular Health Study. CONCLUSION: Accumulation of CML may be an adverse health consequence of SDB.

A modified Bilirubin-induced neurologic dysfunction (BIND-M) algorithm is useful in evaluating severity of jaundice in a resource-limited setting.

BACKGROUND: Severe neonatal jaundice with associated acute bilirubin encephalopathy occurs frequently in low- and middle-income countries, where advanced diagnostic technology is in short supply. In an effort to facilitate the physical diagnosis of acute bilirubin encephalopathy, we pilot-tested a modified bilirubin induced neurologic dysfunction scoring algorithm in a group of pediatric trainees (residents) and their mentors (consultants) in a resource-constrained setting. METHODS: Jaundiced Nigerian infants were examined by consultant and resident pediatricians. The modified bilirubin induced neurologic dysfunction score assigned by residents was compared with the clinical diagnosis of acute bilirubin encephalopathy by expert consultants. Demographic information was obtained. Known risk factors were also evaluated among infants with and without acute bilirubin encephalopathy in addition to exploratory analyses. Data were analyzed by Statistical Analysis System; statistical significance was set at p < 0.05. RESULTS: Three hundred and thirty three paired modified bilirubin induced neurologic dysfunction scores (333) were analyzed and showed excellent agreement (weighted Kappa coefficient 0.7969) between residents and consultants. A modified bilirubin induced neurologic dysfunction score greater than or equal to 3 was highly predictive of a clinical diagnosis of acute bilirubin encephalopathy, with sensitivity of 90.7%, specificity of 97.7%, positive predictive value of 88.9%, and negative predictive value of 98.2%. Exposure to mentholated products was strongly associated with increased risk of acute bilirubin encephalopathy among those with known glucose-6-phosphate dehydrogenase deficiency (odds ratio = 73.94; 95% confidence interval = 5.425-infinity) as well as among those whose G6PD phenotype was unknown (odds ratio = 25.88; 95% confidence interval = 2.845-235.4). CONCLUSIONS: The modified bilirubin induced neurologic dysfunction score for neonatal jaundice can be assigned reliably by both residents and experienced pediatricians in resource-limited settings as reflected in the algorithm's sensitivity and specificity. It may be useful for predicting the development and severity of acute bilirubin encephalopathy in neonates.

Cardiovascular disease among women with and without diabetes mellitus and bilateral oophorectomy.

AIMS: Women with type-2 diabetes (DM2) are at high risk of cardiovascular disease (CVD) which may be partly due to increased ovarian androgen production. Since the association of bilateral oophorectomy (BSO) with CVD remains controversial, we evaluated whether BSO is inversely associated with CVD among DM2. METHODS: Data were obtained from a national sample of 9599 postmenopausal women. Adjusted estimates and 95% confidence intervals (CIs) were calculated using logistic and Cox regression. RESULTS: At baseline 2426 women had type-2 diabetes, of whom 580 had BSO. DM2 had adverse CVD risk profiles compared to women without diabetes, as did women with BSO with or without diabetes compared to those with intact ovaries. In DM2, BSO was positively associated with prevalent CVD (odds ratio: 1.63, 95%CI: 1.16-2.30). However, the higher odds were limited to women who had BSO before age 45 years (OR: 2.11, CI: 1.45-3.08). During a mean follow-up of 12.7 years, BSO in DM2 was positively associated with CVD mortality (hazard ratio: 2.23, CI: 1.25-3.99). Among women with BSO, those with family members who had MI before age 50 had elevated odds of CVD (OR: 2.29, CI: 1.56-3.37) compared to those without such family history (OR: 0.90, CI: 0.67-1.20), Pinteraction=0.04. CONCLUSIONS: The risk of CVD is increased not decreased with BSO in DM2. Further, we propose that the association of BSO and CVD in young women with diabetes may partly reflect genetic susceptibility to CVD rather than an effect of ovarian hormones.

Associations between genetic variants in the TGF-ß signaling pathway and breast cancer risk among Hispanic and non-Hispanic white women.

The TGF-ß signaling pathway has a significant role in breast cancer initiation and promotion by regulating various cellular processes. We evaluated whether genetic variation in eight genes (TGF-ß1, TGF-ß2, TGF-ßR1, TGF-ßR2, TGF-ßR3, RUNX1, RUNX2, and RUNX3) is associated with breast cancer risk in women from the Breast Cancer Health Disparities Study. A total of 3,524 cases (1,431 non-Hispanic whites (NHW); 2,093 Hispanics/Native Americans(NA)) and 4,209 population-based controls (1,599 NHWs; 2,610 Hispanics/NAs) were included in analyses. Genotypes for 47 single nucleotide polymorphisms (SNPs) were determined. Additionally, 104 ancestral informative markers estimated proportion of NA ancestry. Associations with breast cancer risk overall, by menopausal status, NA ancestry, and estrogen receptor (ER)/progesterone receptor tumor phenotype were evaluated. After adjustment for multiple comparisons, two SNPs were significantly associated with breast cancer risk: RUNX3 (rs906296 ORCG/GG = 1.15 95 % CI 1.04-1.26) and TGF-ß1 (rs4803455 ORCA/AA = 0.89 95 % CI 0.81-0.98). RUNX3 (rs906296) and TGF-ßR2 (rs3773644) were associated with risk in pre-menopausal women (p adj = 0.002 and 0.02, respectively) and in those with intermediate to high NA ancestry (p adj = 0.04 and 0.01, respectively). Self-reported race was strongly correlated with NA ancestry (r = 0.86). There was a significant interaction between NA ancestry and RUNX1 (rs7279383, p adj = 0.04). Four RUNX SNPs were associated with increased risk of ER- tumors. Results provide evidence that genetic variation in TGF-ß and RUNX genes are associated with breast cancer risk. This is the first report of significant associations between genetic variants in TGF-ß and RUNX genes and breast cancer risk among women of NA ancestry.

The association of drinking water quality and sewage disposal with Helicobacter pylori incidence in infants: the potential role of water-borne transmission.

The mode of transmission of Helicobacter pylori, a bacterium causing gastric cancer and peptic ulcer disease, is unknown although waterborne transmission is a likely pathway. This study investigated the hypothesis that access to treated water and a sanitary sewerage system reduces the H. pylori incidence rate, using data from 472 participants in a cohort study that followed children in Juarez, Mexico, and El Paso, Texas, from April 1998, with caretaker interviews and the urea breath test for detecting H. pylori infection at target intervals of six months from birth through 24 months of age. The unadjusted hazard ratio comparing bottled/vending machine water to a municipal water supply was 0.71 (95% confidence interval (CI): 0.50, 1.01) and comparing a municipal sewer connection to a septic tank or cesspool, 0.85 (95% CI: 0.60, 1.20). After adjustment for maternal education and country, the hazard ratios decreased slightly to 0.70 (95% confidence interval: 0.49, 1.00) and 0.77 (95% confidence interval: 0.50, 1.21), respectively. These results provide moderate support for potential waterborne transmission of H. pylori.

Incidence of extranodal non-Hodgkin lymphomas among whites, blacks, and Asians/Pacific Islanders in the United States: anatomic site and histology differences.

BACKGROUND: Extranodal non-Hodgkin lymphoma (NHL) accounts for much of the increase in NHL incidence in the past three decades in the United States, but its descriptive epidemiology is scarce in the literature. METHODS: Incidence data for the years 1999-2003 were from 38 population-based cancer registries, covering 82% of US population. We grouped anatomic sites of extranodal NHLs according to the Surveillance, Epidemiology, and End Results (SEER) site recodes, and histology subtypes according to the nested classification of lymphoid neoplasms developed by the Pathology Working Group of the International Lymphoma Epidemiology Consortium. RESULTS: Blacks and Asians/Pacific Islanders (APIs) experienced incidence rates about the same as or lower than whites' for B-cell extranodal NHL as a whole and most of its histologic subtypes. The significant exceptions are: API men had a 40% higher rate of marginal zone lymphoma (MZL) than white men, and API women had a 12% higher rate of diffuse large B-cell lymphoma (DLBCL) than white women. The rates of all T-cell extranodal NHLs combined and peripheral T-cell lymphoma (PTCL) among black women exceeded those of white women by 46% and 18%, respectively. Blacks also had higher rates of mycosis fungoides (MF) than whites (28% higher for men and 99% higher for women). The most common sites of extranodal NHL are stomach, skin, and oral cavity and pharynx. Compared with whites, blacks had either lower or similar incidence of NHL for all sites except skin for women while APIs had higher rates of NHL of the stomach, nose/nasal cavity/middle ear, colorectum (women only), and brain (men only). Age was associated with race- and sex-specific differences in histology-specific incidence rates. CONCLUSION: While blacks and APIs had lower or similar overall incidence rates for extranodal NHL, they experienced excessive rates in some subtypes. Blacks had higher rates of the two most common types of T-cell extranodal NHL and APIs had higher rate of the two common types of B-cell types than whites. Distinct race-specific patterns in histology- and site-specific incidence of extranodal NHL may implicate racial differences in risk factor exposure and/or genetic predisposition.

Cancer incidence patterns among adolescents and young adults in the United States.

OBJECTIVE: The purpose of this study was to examine age-specific cancer incidence patterns among adolescents and young adults (ages 15--49). METHOD: Cancer incidence data for 1995--1999 from 22 population-based central cancer registries, covering about 47% of the US population, were used. Relative frequencies and average annual age-specific incidence rates per 100,000 person-year were computed for the five-year age groups from age 15--19 years through 45--49 years. Tests of significance for comparison were at a level of p<0.05. RESULTS: The age at crossover from a predominance of non-epithelial cancers to a predominance of epithelial cancers during adolescence and young adulthood varied by gender and race. Epithelial cancer became the predominant type of tumor after age 40 years among males while it was the predominant type after age 25 years among females. There was also a shift in the top five cancer types with increasing age, which varied by race and gender. Epithelial cancers of the thyroid, breast, ovary, and cervix uteri started to increase sharply among young women in their 20s while among males epithelial cancers rarely occurred until the early 30s (ages 30--34). Cancers of the female breast, colon and rectum, and lung began to occur at an earlier age and increased more sharply among blacks than among whites. However, the incidence rates of epithelial thyroid and ovarian cancers rose more quickly among whites than blacks. Non-Hodgkin lymphoma and soft tissue sarcoma (excluded Kaposi's sarcoma) increased with age among both whites and blacks but the rates were significantly higher among blacks than among whites. Both Kaposi's sarcoma and testicular cancer incidence increased with age and peaked in the early 30s (ages 30--34). The former was significantly higher among blacks than whites while the latter was significantly higher among whites than blacks. Cervical cancer incidence leveled off when white women reached their 30s, but for black women the rate continued to rise with advancing age. Cutaneous melanoma rates were significantly higher among females than among males between the ages of 15 and 39. Conclusion Cancer incidence patterns among adolescents and young adults are distinctive. Specific cancer prevention and control strategies should be targeted accordingly and tailored to their specific needs.

Subsite-specific colorectal cancer incidence rates and stage distributions among Asians and Pacific Islanders in the United States, 1995 to 1999.

OBJECTIVE: This study examined subsite-specific colorectal cancer incidence rates and stage distributions for Asians and Pacific Islanders (API) and compared the API data with data for Whites and African Americans. METHODS: Data included 336,798 invasive colorectal cancer incident cases for 1995 to 1999 from 23 population-based central cancer registries, representing about two thirds of API population in the United States. Age-adjusted rates, using the 2000 U.S. standard population, and age-specific rates and stage distributions were computed by anatomic subsite, race, and gender. All rates were expressed per 100,000. SEs and rate ratios were calculated for rate comparison. A significance level of 0.05 was used for all analyses. RESULTS: Overall, age-adjusted colorectal cancer incidence rates were significantly lower in API than in Whites and African Americans across anatomic subsites, particularly for proximal colon cancer in which rates were 40% to 50% lower in API males and females. Exception to this pattern was the significantly (10%) higher rectal cancer incidence rate in API males than in African American males. The incidence patterns by anatomic subsite within API differed from those of Whites and African Americans. Among API, the rate of rectal cancer (19.2 per 100,000) was significantly higher than the rates of proximal (15.2 per 100,000) and distal (17.7 per 100,000) colon cancers in males, with little variations in rates across anatomic subsites in females. In contrast, among White and African American males and females, proximal colon cancer rates were over 25% higher than the rates of distal colon and rectal cancers. Increases in age-specific rates with advancing age were more striking for proximal colon cancer than for distal colon and rectal cancers in Whites and African Americans, while age-specific rates were very similar for different subsites in API with parallel increases with advancing age, especially in API males. Similar to Whites and African Americans, in API, proximal colon cancers (32% to 35%) were also less likely to be diagnosed with localized stage compared with distal colon (38% to 42%) and rectal (44% to 52%) cancers. CONCLUSION: The patterns of subsite-specific colorectal cancer incidence in API, especially API males, differ from those of Whites and African Americans. Similar to Whites and African Americans, lower percentage of localized disease in API for proximal colon cancer than for distal colon and rectal cancers was also observed.

Diet and stomach cancer risk in Warsaw, Poland.

Some of the world's highest rates of stomach cancer are found in Poland. Reasons for the increased incidence are not known, but high intake of sausages and other preserved foods and low intake of fresh fruits and vegetables may be involved. A case-control study comprising residents newly diagnosed with stomach cancer during 1994-96 and controls randomly selected from the general population was conducted in Warsaw, Poland. Standardized interviews were conducted to ascertain usual consumption of 118 common foods and beverages and other exposures. Using data from direct interviews with 274 cases and 463 controls, odds ratios of stomach cancer were calculated as estimates of risks associated with dietary factors, adjusting for age, sex, education, smoking, and caloric intake. Risk of stomach cancer was inversely related to intake of total fruits and dark green-yellow vegetables and to indices of vitamins C and E and alpha- and beta-carotenes. However, risk was not significantly increased among those with high intake of pickled/salted vegetables and sausages. Risks were positively associated with increased intake of breads/cereals/rice/pasta and other refined grains, as well as a high carbohydrate index. Our findings add to the evidence of a protective effect of fruits and certain vegetables on stomach cancer risk, but do not indicate that high intake of sausage and other preserved foods typical in the Polish diet has contributed to the country's elevated stomach cancer incidence. Our data also suggest that high carbohydrate consumption may influence risk, but further confirmation is needed.

N-nitroso compounds and mutagens in Chinese fermented (sour) corn pancakes.

Stomach cancer rates in rural Linqu County, Shandong Province, China, are exceptionally high. A previous case-control study revealed that the risk of stomach cancer was 30% higher among those who consumed sour (fermented) corn pancakes at least daily. A previous study of the sour pancakes reported volatile nitrosamines in most specimens, and almost half reportedly showed mutagenic activity. Few households currently consume sour pancakes, and the duration of fermentation has been shortened. We tested specimens of pancake batter and sour pancakes from Linqu County for mutagenic activity using the Ames test; for N-nitroso compounds (NOC) we used the Nitrolite-thermal energy analysis (TEA) method. Results of the Ames test were inconclusive: only 1 out of 15 cooked pancakes showed a positive mutagenic response, and all 15 batter specimens were negative; however, several batter specimens showed a weakly positive trend of mutagenicity with extract concentration. Our assay for total nitroso compounds was weakly positive in only 1 out of 15 specimens of sour pancake batter. That specimen was also tested by gas chromatography-TEA for nitrosaminoacids and volatile nitrosamines, but none were detected. It seems unlikely that the Chinese sour pancakes are significantly contaminated by NOC or other mutagens.

Serum antibodies to Helicobacter pylori and the CagA antigen do not explain differences in the prevalence of precancerous gastric lesions in two Chinese populations with contrasting gastric cancer rates.

Incidence and mortality rates for gastric cancer in rural People's Republic of China differ greatly over short distances. In Shandong Province, we studied asymptomatic adult subjects from Bei Duan village (n = 196) in Linqu County (a high-risk area for gastric cancer) and from Shi Huang village (n = 192) in Cangshan County (a low-risk area for gastric cancer). The prevalence of advanced precancerous gastric lesions (APGL) was assessed by microscopic examination of endoscopic stomach biopsies. ELISAs were used to detect serum IgG to Helicobacter pylori whole-cell antigen and to the CagA protein. A logistic regression model was used to quantify the role of the two H. pylori seromarkers in explaining the differences in prevalence of APGL between the two villages after adjusting for age and sex. The prevalence of APGL was much greater in Bei Duan than in Shi Huang. Although H. pylori seroprevalence by the whole-cell ELISA was similar in the two populations, seroprevalence of CagA was significantly greater in Bei Duan. Although age, sex, and both H. pylori seromarkers were associated with APGL in the logistic regression model, the effect of village of residence remained strong after adjustment for all four covariates. Only a relatively small proportion of the difference in prevalence of APGL between these two rural Chinese populations can be explained by differences in H. pylori or CagA seroprevalence.

Cancer in Korean war navy technicians: mortality survey after 40 years.

This study reports on over 40 years of mortality follow-up of 40,581 Navy veterans of the Korean War with potential exposure to high-intensity radar. The cohort death rates were compared with mortality rates for White US men using standardized mortality ratios, and the death rates for men in occupations considered a priori to have high radar exposure were compared with the rates for men in low-exposure occupations using Poisson regression. Deaths from all diseases and all cancers were significantly below expectation overall and for the 20,021 sailors with high radar exposure potential. There was no evidence of increased brain cancer in the entire cohort (standardized mortality ratio (SMR) = 0.9, 95% confidence interval (CI): 0.7, 1.1) or in high-exposure occupations (SMR = 0.7, 95% CI: 0.5, 1.0). Testicular cancer deaths also occurred less frequently than expected in the entire cohort and high-exposure occupations. Death rates for several smoking-related diseases were significantly lower in the high-exposure occupations. Nonlymphocytic leukemia was significantly elevated among men in high-exposure occupations but in only one of the three high-exposure occupations, namely, electronics technicians in aviation squadrons (SMR = 2.2, 95% CI: 1.3, 3.7). Radar exposure had little effect on mortality in this cohort of US Navy veterans.