Self-report versus ultrasound measurement of uterine fibroid status.

BACKGROUND: Much of the epidemiologic research on risk factors for fibroids, the leading indication for hysterectomy, relies on self-reported outcome. Self-report is subject to misclassification because many women with fibroids are undiagnosed. The purpose of this analysis was to quantify the extent of misclassification and identify associated factors. METHODS: Self-reported fibroid status was compared to ultrasound screening from 2046 women in Right From The Start (RFTS) and 869 women in the Uterine Fibroid Study (UFS). Log-binomial regression was used to estimate sensitivity (Se) and specificity (Sp) and examine differences by ethnicity, age, education, body mass index, parity, and miscarriage history. RESULTS: Overall sensitivity was ≤0.50. Sensitivity was higher in blacks than whites (RFTS: 0.34 vs. 0.23; UFS: 0.58 vs. 0.32) and increased with age. Parous women had higher sensitivity than nulliparae, especially in RFTS whites (Se ratio=2.90; 95% confidence interval [CI]: 1.51, 5.60). Specificity was 0.98 in RFTS and 0.86 in UFS. Modest ethnic differences were seen in UFS (Sp ratio, black vs. white=0.90; 95% CI: 0.81, 0.99). Parity was inversely associated with specificity, especially among UFS black women (Sp ratio=0.84; 95% CI: 0.73, 0.97). Among women who reported a previous diagnosis, a shorter time interval between diagnosis and ultrasound was associated with increased agreement between the two measures. CONCLUSIONS: Misclassification of fibroid status can differ by factors of etiologic interest. These findings are useful for assessing (and correcting) bias in studies using self-reported clinical diagnosis as the outcome measure.

Obesity and prostate cancer aggressiveness among African and Caucasian Americans in a population-based study.

BACKGROUND: This study evaluated obesity and prostate cancer aggressiveness relationship in a population-based incident prostate cancer study. METHODS: The North Carolina-Louisiana Prostate Cancer Project includes medical records data for classification of prostate cancer aggressiveness at diagnosis by using clinical criteria for 1,049 African American (AA) and 1,083 Caucasian American (CA) participants. An association between prostate cancer aggressiveness and obesity, measured using body mass indices (BMI) and waist-to-hip ratio (WHR), was assessed using ORs and 95% CIs adjusted for confounders. RESULTS: A significantly positive association was found between prostate cancer aggressiveness and obesity. The ORs for high aggressive prostate cancer among prediagnosis obese and severely obese were 1.48 (95% CI = 1.02-2.16) and 1.98 (95% CI = 1.31-2.97), respectively, compared with normal weight research subjects. Race-stratified results suggested the association is stronger among CAs. Interaction model showed that normal weight AAs had more aggressive prostate cancer than normal weight CAs (OR = 2.69, 95% CI = 1.36-5.30); severe obesity was associated with aggressive disease in AAs (OR = 3.90, 95% CI = 1.97-7.75). WHR > 0.98 among all research subjects adjusted for race was significantly associated with high aggressive prostate cancer (OR = 1.42, 95% CI = 1.00-2.00) when compared with WHR < 0.90. The stratified result is less clear among AAs. CONCLUSIONS: This study shows a positive association between obesity and aggressive prostate cancer. AAs have more aggressive prostate cancer in general than CAs even at normal weight. Therefore, the association between obesity and aggressiveness is not as evident in AAs as in CAs. IMPACT: This study provides a unique opportunity to examine impact of race on obesity and high aggressive prostate cancer relationship.

Potential risk factors associated with subtypes of uterine leiomyomata.

OBJECTIVE: To compare potential risk factors for uterine leiomyomata (UL) subtypes among premenopausal African American and Caucasian women. METHODS: This cross-sectional study included 986 premenopausal women, aged 35 to 49 years old, from the National Institute of Environmental Health Sciences (NIEHS) Uterine Fibroid Study (UFS). Uterine leiomyomata were subtyped as submucosal, intramural/subserosal, and diffuse, based on ultrasound examinations. RESULTS: For both ethnic groups, age, age at menarche, body mass index, and current physical activity had similar associations across the 3 UL subtypes. Inverse associations with pregnancies after age 24 appeared to be stronger for the submucosal subtype. Current smoking was associated only with diffuse UL (adjusted odds ratio [aOR] = 1.97, 95% CI: 1.11, 3.51 in African Americans, aOR = 3.00, 95% CI: 1.07, 8.38 in Caucasians). CONCLUSIONS: Although the 2 focal UL subtypes had similar risk factor profiles, the diffuse UL subtype appeared to have a distinctive risk profile with regard to current smoking. Further study of the diffuse heterogeneity seen with uterine ultrasound is needed.

New directions in the epidemiology of uterine fibroids.

Although uterine leiomyomata (fibroids) have been the leading indication for hysterectomy in the United States for decades, the epidemiological data on fibroid prevalence and risk factors are limited. Given the hormonal dependence of fibroids, most earlier studies focused on reproductive or hormonal factors. Recent analyses have extended that focus to other areas. We present previously unpublished data on the association between reproductive tract infections and fibroids that highlight the need for more detailed studies. Our review suggests that metabolic, dietary, stress, and environmental factors may also play a role in fibroid development.

A case-control study of tobacco use and other non-occupational risk factors for lymphoma subtypes defined by t(14; 18) translocations and bcl-2 expression.

OBJECTIVE: We re-evaluated reported associations between tobacco use and other factors and non-Hodgkin lymphoma (NHL) t(14; 18)-subtypes based on fluorescence in situ hybridization (FISH) assays believed to be more sensitive than polymerase chain reaction (PCR), previously used for detecting t(14; 18). METHODS: Commercial FISH assays and bcl-2 immunostaining were performed on paraffin sections to determine t(14; 18) and bcl-2 case-subtypes. Polytomous logistic regression models estimated associations between NHL case-subtypes (versus 1,245 population-based controls) and tobacco use as well as other factors. RESULTS: Adjusting for age, state, and proxy status, t(14; 18)-negative NHL was associated with any tobacco use (vs. no tobacco use, OR = 1.9, 95% CI = 1.0-3.5), including current smoking (vs. no cigarette use, OR = 1.9, 95% CI = 1.1-3.2). Tobacco exposures were not clearly associated with t(14; 18)-positive NHL or bcl-2 case-subtypes. Hair-dye use and family history of a hemolymphatic cancer were associated with t(14; 18)-negative NHL, but the number of exposed cases was small. CONCLUSIONS: The association between t(14; 18)-negative NHL and cigarette smoking was unexpected given previous evidence of associations between smoking and follicular lymphoma (which is largely t(14; 18)-positive). Future studies characterizing additional molecular characteristics of t(14; 18)-negative NHL may help determine whether the association with smoking may have been causal versus an artifact of chance or bias.

Uterine leiomyomata associated with self-reported stress urinary incontinence.

AIMS: To investigate the association between the presence and characteristics of uterine leiomyomata (UL) and self-reported stress urinary incontinence (SUI). METHODS: The study included 836 premenopausal participants (474 African American and 362 Caucasian) in the National Institute of Environmental Health Sciences (NIEHS) Uterine Fibroid Study. UL were characterized at baseline with ultrasound screening, and SUI was assessed at follow-up (after 4 years, on average). Linear risk models were used to estimate adjusted prevalence differences (aPD) and 95% confidence intervals (CI), controlling for age, ethnicity, body mass index (BMI), and number of deliveries. RESULTS: Compared with women without UL, SUI prevalence was higher among women with any UL (aPD = 7.4%, 95% CI 0.4-14.3) and women with UL 2-4 cm (aPD = 9.6%, 95% CI 1.3-17.9). Marginally significant results were found for the presence of UL > or =4 cm and anterior UL > or =2 cm. CONCLUSIONS: The observed 7% increase in prevalence of this common condition for women with UL is of clinical importance. Further research is needed before concluding that treatment for larger UL might enhance SUI treatment in some women.

trans-Fatty acid consumption and its association with distal colorectal cancer in the North Carolina Colon Cancer Study II.

Recently, the potential health effects of trans-fatty acid consumption have raised concerns. A few studies have examined the risk of colorectal cancer with increasing consumption of trans-fatty acids, but none investigated the risk of rectal cancer, which may have different risk factors than colon cancer. Our objective was to explore the relationship between trans-fatty acid consumption and distal colorectal (sigmoid, rectosigmoid, and rectal) cancer using a case-control study of Whites (n = 1,516) and African Americans (n = 392) in North Carolina from 2001 to 2006. Matched cases and controls were interviewed about demographic information, lifestyle factors, and diet. White cases reported higher mean consumption of trans-fatty acid than White controls, but mean consumption was similar for African American cases and controls. Relative to the lowest quartile, the highest quartiles of energy-adjusted trans-fatty acid consumption were positively associated with distal colorectal cancer for Whites [adjusted ORs for the third and fourth quartiles are 1.54 (95%CI: 1.12, 2.13) and 1.45 (95%CI: 1.04, 2.03), respectively]. Consumption was not associated with distal colorectal cancer in African Americans [adjusted ORs for the third and fourth quartiles are 0.98 (95%CI: 0.47, 2.05) and 0.87 (95%CI 0.42, 1.81), respectively]. In conclusion, high consumption of trans-fatty acids was positively associated with distal colorectal cancer among Whites.

Non-Hodgkin lymphoma (NHL) subtypes defined by common translocations: utility of fluorescence in situ hybridization (FISH) in a case-control study.

We used fluorescence in situ hybridization (FISH) assays to identify t(14;18) translocations in archival paraffin-embedded tumor sections from non-Hodgkin lymphoma (NHL) cases enrolled in a population-based study. t(14;18) was identified in 54% of 152 cases, including 39% of diffuse large cell lymphomas (26 of 66 cases) and 84% of follicular lymphomas (36 of 43 cases). Eighty-seven percent of t(14;18)-positive cases and 57% of t(14;18)-negative cases expressed bcl-2. FISH assays detected twice as many t(14;18)-positive follicular lymphomas as PCR assays. Overall, study findings support the use of FISH assays to detect t(14;18) in archival tumor samples for epidemiologic studies of NHL subtypes.

Associations between trans fatty acid consumption and colon cancer among Whites and African Americans in the North Carolina colon cancer study I.

Disparities in incidence and mortality rates of colon cancer exist between Whites and African Americans. Prior studies examined the association between trans fatty acid consumption and colorectal cancer, but none assessed this possible relationship within a large study population of African Americans and Whites. Using data from a population-based, case-control study in North Carolina, we investigated this association with attention to possible racial differences. Cases and matched controls were queried on demographic characteristics, lifestyle factors, medical history, and diet. Cases reported higher daily consumption (g/day) of trans fatty acids (mean = 5.9, SD = 2.9, median = 5.5, IQR = 3.8-7.5) compared to controls (mean = 5.2, SD = 2.4, median = 4.7, IQR = 3.5-6.4). Energy-adjusted trans fatty acid consumption was not associated with colon cancer. Compared to participants in the lowest quartile of consumption, those in the highest quartile had an adjusted odds ratio of 1.01 (95% confidence interval 0.69, 1.49) for Whites and 0.99 (95% confidence interval 0.61, 1.62) for African Americans. No association was found between increased consumption of trans fatty acid and specific tumor location (proximal or distal colon). In conclusion, trans fatty acid consumption is not associated with colon cancer and does not contribute to disparities in colon cancer rates.

Reproductive and hormonal risk factors for ductal carcinoma in situ of the breast.

One-fifth of all newly diagnosed breast cancer cases are ductal carcinoma in situ (DCIS), but little is known about DCIS risk factors. Recent studies suggest that some subtypes of DCIS (high grade or comedo) share histopathologic and epidemiologic characteristics with invasive disease, whereas others (medium or low grade or non-comedo) show different patterns. To investigate whether reproductive and hormonal risk factors differ among comedo and non-comedo types of DCIS and invasive breast cancer (IBC), we used a population-based case-control study of 1,808 invasive and 446 DCIS breast cancer cases and their age and race frequency-matched controls (1,564 invasive and 458 DCIS). Three or more full-term pregnancies showed a strong inverse association with comedo-type DCIS [odds ratio (OR), 0.53; 95% confidence interval (95% CI), 0.30-0.95] and a weaker inverse association for non-comedo DCIS (OR, 0.73; 95% CI, 0.42-1.27). Several risk factors (age at first full-term pregnancy, breast-feeding, and age at menopause) showed similar associations for comedo-type DCIS and IBC but different associations for non-comedo DCIS. Ten or more years of oral contraceptive showed a positive association with comedo-type DCIS (OR, 1.31; 95% CI, 0.70-2.47) and IBC (OR, 2.33; 95% CI, 1.06-5.09) but an inverse association for non-comedo DCIS (OR, 0.51; 95% CI, 0.25-1.04). Our results support the theory that comedo-type DCIS may share hormonal and reproductive risk factors with IBC, whereas the etiology of non-comedo DCIS deserves further investigation.

Epstein-Barr virus WZhet DNA can induce lytic replication in epithelial cells in vitro, although WZhet is not detectable in many human tissues in vivo.

OBJECTIVE: WZhet is a rearranged and partially deleted form of the Epstein-Barr virus (EBV) genome in which the BamH1W region becomes juxtaposed with and activates BZLF1, resulting in constitutive viral replication. We tested whether WZhet induces viral replication in epithelial cells, and we studied its prevalence in a wide range of lesional tissues arising in vivo. METHODS: A quantitative real-time PCR assay targeting EBV WZhet DNA was developed to measure this recombinant form of the EBV genome. RESULTS: WZhet DNA was undetectable in any of 324 plasma or paraffin-embedded tissue samples from patients with EBV-associated and EBV-negative disorders. These included specimens from patients with Hodgkin or non-Hodgkin lymphoma, post-transplant lymphoproliferation, nasopharyngeal or gastric adenocarcinoma, and infectious mononucleosis. However, WZhet DNA was detected in vitro in EBV-infected AGS gastric cancer cells. Additionally, transient transfection of infected AGS gastric cancer cells showed that viral replication could be induced by a WZhet plasmid. CONCLUSION: This is the first evidence that WZhet induces the EBV lytic cycle in an epithelial cell line. Our negative findings in natural settings suggest that WZhet is a defective viral product that thrives in the absence of a host immune system but is rarely present in vivo.

IGF-I and IGFBP-3 polymorphisms in relation to circulating levels among African American and Caucasian women.

Circulating insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels have been associated with common diseases. Although family-based studies suggest that genetic variation contributes to circulating IGF-I and IGFBP-3 levels, analyses of associations with multiple IGF-I and IGFBP-3 single nucleotide polymorphisms (SNP) have been limited, especially among African Americans. We evaluated 30 IGF-I and 15 IGFBP-3 SNPs and estimated diplotypes in association with plasma IGF-I and IGFBP-3 among 984 premenopausal African American and Caucasian women. In both races, IGFBP-3 rs2854746 (Ala32Gly) was positively associated with plasma IGFBP-3 (CC versus GG mean difference among Caucasians, 631 ng/mL; 95% confidence interval, 398-864; African Americans, 897 ng/mL; 95% confidence interval, 656-1,138), and IGFBP-3 diplotypes with the rs2854746 GG genotype had lower mean IGFBP-3 levels than reference diplotypes with the CG genotype, whereas IGFBP-3 diplotypes with the CC genotype had higher mean IGFBP-3 levels. IGFBP-3 rs2854744 (-202 A/C) was in strong linkage disequilibrium with rs2854746 in Caucasians only, but was associated with plasma IGFBP-3 in both races. Eight additional IGFBP-3 SNPs were associated with >or=5% differences in mean IGFBP-3 levels, with generally consistent associations between races. Twelve IGF-I SNPs were associated with >or=10% differences in mean IGF-I levels, but associations were generally discordant between races. Diplotype associations with plasma IGF-I did not parallel IGF-I SNP associations. Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians but provides less evidence that IGF-I SNPs affect plasma IGF-I levels.

Association between p53 codon 72 genetic polymorphism and tobacco use and lung cancer risk.

Lung cancer (LCa) is the leading cause of death by cancer in men. Genetic and environmental factors play a synergistic role in its etiology. We explore in 111 lung cancer cases and 133 unrelated noncancer controls the gene-environment interaction (G x E) between p53cd72 polymorphism variants and smoking and the effect on LCa risk in two kinds of case-control designs. We assessed the interaction odds ratio (IOR) using an adjusted unconditional logistic model. We found a significant and positive interaction association between Pro* allele carriers and smoking habits in both case-control and case-only designs: IOR = 3.90 (95% confidence interval [CI] = 1.10-13.81) and 3.05 (95% CI = 1.63-5.72), respectively. These exploratory results suggest a synergistic effect of the smoking habit and the susceptibility of the Pro allele on lung cancer risk compared with each risk factor alone.

Reproductive factors and hormone use and risk of adult gliomas.

Previous research suggests there may be a hormonal influence on glioma risk as evidenced by lower rates in females, change in incidence rates around ages at menarche and menopause, and presence of hormone receptors in glial tumors. Using the large San Francisco Bay Area Adult Glioma Study, we investigated whether reported reproductive factors and hormone use were associated with gliomas overall or with histologic subtypes among female cases (n = 619) and controls (n = 650). We found that reproductive factors were generally not associated with gliomas. Weak to moderately elevated odds ratios were observed for self-reported later age at menarche (14+ vs. 12-13 years old: adjusted odds ratio (AOR) = 1.39, 95% confidence interval (CI): 1.02-1.89), particularly for non-glioblastoma histologies (AOR = 1.64, 95% CI: 1.11-2.43). Inverse associations were observed for ever self-reported use of exogenous hormones (oral contraceptive use: AOR = 0.72, 95% CI: 0.53-0.99; postmenopausal hormone use: AOR = 0.56, CI: 0.37-0.84). However, cumulative hormone exposure defined multiple ways demonstrated no clear pattern of association. The results of this study suggest that any protective effect of hormones on gliomas may be limited to exogenous hormones, but a more detailed history of exogenous hormone use is needed to confirm findings.

Use of nonsteroidal antiinflammatory drugs and distal large bowel cancer in whites and African Americans.

Despite the belief that the etiology of and risk factors for rectal cancer might differ from those for colon cancer, relatively few studies have examined rectal cancer in relation to use of nonsteroidal antiinflammatory drugs (NSAIDs). The authors evaluated the association between NSAIDs and distal large bowel cancer in African Americans and whites, using data from a population-based case-control study of 1,057 incident cases of adenocarcinoma of the sigmoid colon, rectosigmoid junction, and rectum and 1,019 controls from North Carolina (2001-2006). NSAID use was inversely associated with distal large bowel cancer in whites (odds ratio (OR) = 0.60, 95% confidence interval (CI): 0.46, 0.79). The inverse association was evident for all types of NSAIDs but was slightly stronger with prescription NSAIDs, particularly selective cyclooxygenase 2 inhibitors (OR = 0.38, 95% CI: 0.25, 0.56). Compared with whites, a relatively weak inverse association was found in African Americans (OR = 0.87, 95% CI: 0.55, 1.40), although odds ratio heterogeneity by race could not be confirmed (P = 0.21). In addition, the strength of the association with NSAIDs varied by tumor location, suggesting more potent effects for rectal and rectosigmoid cancers than for sigmoid cancer. The chemopreventive potential of NSAIDs might differ by population and by tumor characteristics.