Biomedical subjects

Argyrios Ziogas

Publications and source records attributed to Argyrios Ziogas.

At least 19 recordsLinked to original sources

PubMed2007

Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival.

Elevated polyamine and nitric oxide levels (both derived from arginine) promote tumorigenesis, whereas non-steroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal cancer (CRC) incidence in experimental and epidemiologic studies. We investigated dietary arginine-induced intestinal tumorigenesis and NSAID-inhibitory effects in Apc(Min/+) mice differentially expressing nitric oxide synthase-2 (Nos2). We also studied effects of estimated arginine exposures through meat consumption on tumor characteristics and survival in human CRC cases. Dietary arginine increased high-grade colon adenoma incidence in Apc(Min/+)Nos2(+/+) mice, but not in Nos2 knockout mice. Additionally, celecoxib suppressed intestinal steady state ornithine decarboxylase RNA levels (p < 0.001), induced steady state spermidine/spermine N(1)-acetyltransferase RNA levels (p = 0.002), decreased putrescine levels (p = 0.04) and decreased tumor number in the small intestines of Apc(Min/+)Nos2(+/+) mice (p = 0.0003). Five hundred and eleven cases from our NCI-supported CRC gene-environment study were analyzed based on self-reported meat (as a surrogate for arginine) consumption. Familial CRC cases (n = 144) in the highest meat consumption quartile (Q4) had no statistically significant differences in tumor grade compared to cases in Q1-Q3 (p = 0.32); however, they were observed to have decreased overall survival (OS) (10-year OS = 42% vs. 65%; p = 0.017), and increased risk of death in an adjusted analysis (hazards ratio [HR] = 2.24; p = 0.007). No differences in tumor grade, OS or adjusted HR were observed for sporadic CRC cases (n = 367) based on meat consumption. Our results suggest important roles for arginine and meat consumption in CRC pathogenesis, and have implications for CRC prevention.

Acetyltransferases↗

PubMed2007

Diet and risk of ovarian cancer in the California Teachers Study cohort.

Dietary phytochemical compounds, including isoflavones and isothiocyanates, may inhibit cancer development but have not yet been examined in prospective epidemiologic studies of ovarian cancer. The authors have investigated the association between consumption of these and other nutrients and ovarian cancer risk in a prospective cohort study. Among 97,275 eligible women in the California Teachers Study cohort who completed the baseline dietary assessment in 1995-1996, 280 women developed invasive or borderline ovarian cancer by December 31, 2003. Multivariable Cox proportional hazards regression, with age as the timescale, was used to estimate relative risks and 95% confidence intervals; all statistical tests were two sided. Intake of isoflavones was associated with lower risk of ovarian cancer. Compared with the risk for women who consumed less than 1 mg of total isoflavones per day, the relative risk of ovarian cancer associated with consumption of more than 3 mg/day was 0.56 (95% confidence interval: 0.33, 0.96). Intake of isothiocyanates or foods high in isothiocyanates was not associated with ovarian cancer risk, nor was intake of macronutrients, antioxidant vitamins, or other micronutrients. Although dietary consumption of isoflavones may be associated with decreased ovarian cancer risk, most dietary factors are unlikely to play a major role in ovarian cancer development.

Adult↗

PubMed2007

Wine and other alcohol consumption and risk of ovarian cancer in the California Teachers Study cohort.

OBJECTIVE: Whether alcohol consumption influences ovarian cancer risk is unclear. Therefore, we investigated the association between alcohol intake at various ages and risk of ovarian cancer. METHODS: Among 90,371 eligible members of the California Teachers Study cohort who completed a baseline alcohol assessment in 1995-1996, 253 women were diagnosed with epithelial ovarian cancer by the end of 2003. Multivariate Cox proportional hazards regression analysis was performed to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Consumption of total alcohol, beer, or liquor in the year prior to baseline, at ages 30-35 years, or at ages 18-22 years was not associated with risk of ovarian cancer. Consumption of at least one glass per day of wine, compared to no wine, in the year before baseline was associated with increased risk of developing ovarian cancer: RR = 1.57 (95% CI 1.11-2.22), P (trend) = 0.01. The association with wine intake at baseline was particularly strong among peri-/post-menopausal women who used estrogen-only hormone therapy and women of high socioeconomic status. CONCLUSIONS: Alcohol intake does not appear to affect ovarian cancer risk. Constituents of wine other than alcohol or, more likely, unmeasured determinants of wine drinking were associated with increased risk of ovarian cancer.

Adolescent↗

PubMed2006

Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer.

INTRODUCTION: There is growing evidence that heritable genetic variation modulates metastatic efficiency. Our previous work using a mouse mammary tumor model has shown that metastatic efficiency is modulated by the GTPase-activating protein encoded by Sipa1 ('signal-induced proliferation-associated gene 1'). The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) within the human SIPA1 gene are associated with metastasis and other disease characteristics in breast cancer. METHOD: The study population (n = 300) consisted of randomly selected non-Hispanic Caucasian breast cancer patients identified from a larger population-based series. Genomic DNA was extracted from peripheral leukocytes. Three previously described SNPs within SIPA1 (one within the promoter [-313G>A] and two exonic [545C>T and 2760G>A]) were characterized using SNP-specific PCR. RESULTS: The variant 2760G>A and the -313G>A allele were associated with lymph node involvement (P = 0.0062 and P = 0.0083, respectively), and the variant 545C>T was associated with estrogen receptor negative tumors (P = 0.0012) and with progesterone negative tumors (P = 0.0339). Associations were identified between haplotypes defined by the three SNPs and disease progression. Haplotype 3 defined by variants -313G>A and 2760G>A was associated with positive lymph node involvement (P = 0.0051), and haplotype 4 defined by variant 545C>T was associated with estrogen receptor and progesterone receptor negative status (P = 0.0053 and P = 0.0199, respectively). CONCLUSION: Our findings imply that SIPA1 germline polymorphisms are associated with aggressive disease behavior in the cohort examined. If these results hold true in other populations, then knowledge of SIPA1 SNP genotypes could potentially enhance current staging protocols.

Abortion, Spontaneous↗

PubMed2006

An inverse association between ovarian cysts and breast cancer in the breast cancer family registry.

Ovarian cysts of several types are common in women of reproductive age. Their etiology is not well understood but is likely related to perturbations in the hypothalamic-pituitary-gonadal axis. The relationship of ovarian cysts to breast cancer risk is not known, although a negative association with polycystic ovarian syndrome has been reported. Incident, invasive female breast cancer cases, population-based controls and unaffected sisters of cases were studied from 3 countries participating in the Breast Cancer Family Registry: Melbourne and Sydney, Australia; the San Francisco Bay Area, USA; and Ontario, Canada. Using the same questionnaire, information was collected on self-reported history of ovarian cysts and other risk factors. Analyses were based on 3,049 cases, 2,344 population controls and 1,934 sister controls from all sites combined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using both unconditional and conditional logistic regression using an offset term to account for sampling fractions at 2 of the sites. A significantly reduced risk of breast cancer was observed for women reporting a history of ovarian cysts (OR = 0.70, 95% CI 0.59-0.82, among all cases and all controls). This risk estimate was similar regardless of control group used, within all 3 sites and in both premenopausal and postmenopausal women (ORs ranging from 0.68-0.75, all 95% CI excluded 1.00). A self-reported history of ovarian cysts was strongly and consistently associated with a reduced risk of breast cancer. Further study of ovarian cysts may increase our understanding of hormonal and other mechanisms of breast cancer etiology.

Adolescent↗

PubMed2006

Dietary fat, fiber, vegetable, and micronutrients are associated with overall survival in postmenopausal women diagnosed with breast cancer.

Relatively few studies have assessed the relationship between dietary intakes and survival after breast cancer diagnosis. We investigated the influence of diet, including dietary fat (percentage energy), fiber, vegetable, and fruit intakes, and micronutrients (folate, carotenoids, and vitamin C) on overall survival in women diagnosed with breast cancer. Subjects were postmenopausal women diagnosed with breast cancer (N = 516) between 1994 and 1995 with a mean survival time of 80 mo (SD: 18). Subjects completed a food frequency questionnaire for the year prior to diagnosis. Cox proportional hazards models were used to measure the relationship between dietary intakes and death due to any cause after breast cancer diagnosis. In the multivariate analysis, we found that the hazard ratio [HR and 95% confidence interval (CI)] of dying in the highest tertile compared to the lowest tertile of total fat, fiber, vegetable, and fruit was 3.12 (95% CI = 1.79-5.44), 0.48 (95% CI = 0.27-0.86), 0.57 (95% CI = 0.35-0.94), and 0.63 (95% CI = 0.38-1.05), respectively (P <or= 0.05 for trend, except for fruit intake). Other nutrients including folate, vitamin C, and carotenoid intakes were also significantly associated with reduced mortality (P <or= 0.05 for trend). These results suggest that in postmenopausal women diagnosed with breast cancer, reduced dietary fat and increased fiber, vegetable, fruit, and other nutrient intakes associated with a plant-based, high-fiber diet improves overall survival after breast cancer diagnosis.

Body Mass Index↗

PubMed2005

Epidemiology of bronchioloalveolar carcinoma: improvement in survival after release of the 1999 WHO classification of lung tumors.

PURPOSE: Classification changes for bronchioloalveolar carcinoma (BAC) by the WHO in May 1999 narrowed its definition. This study was undertaken in an attempt to characterize the impact of these changes on the epidemiology of BAC. PATIENTS AND METHODS: This retrospective study involves data analysis from the population-based Cancer Surveillance Programs of three Southern California counties from 1995 to 2003. BAC cases diagnosed after May 1999 are compared with BAC cases before that time by clinicopathologic variables including survival. RESULTS: Incident cases (11,969) of non-small-cell lung cancer (NSCLC) were analyzed, including 626 cases of BAC (5.2%). Median overall survival (OS) for BAC patients diagnosed after May 1999 (> 53 months) was significantly improved over median OS for BAC patients before May 1999 (32 months; P = .012). This survival benefit remained after adjustment for sex, smoking status, and stage at presentation (hazard ratio for time of diagnosis before May 1999 compared with a diagnosis after May 1999 = 1.43; P = .015). Median OS for non-BAC NSCLC patients diagnosed before May 1999 (9 months) did not differ from the median OS of such patients afterwards (10 months; P = .09). CONCLUSION: This epidemiologic study is the first to demonstrate a survival advantage for BAC patients diagnosed after May 1999 compared with BAC patients diagnosed before this time-a finding that persists after adjustment for sex, smoking status, and stage at presentation. We believe that this observed survival benefit likely reflects changes in the revised 1999 WHO classification.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2005

Feasibility of management of high-grade cervical lesions in a single visit: a randomized controlled trial.

CONTEXT: The incidence of cervical cancer is higher among low-income and minority women who have never undergone a conventional Papanicolaou test or who do not follow up after testing. Screening has been shown to reduce cervical cancer incidence rates. OBJECTIVES: To determine the feasibility and acceptability of immediately treating women with severely abnormal Papanicolaou test results by using a single-visit cervical cancer screening and treatment program and to compare treatment rates and 12-month follow-up rates with those of women who received usual care. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted among 3521 women aged 18 years or older recruited between January 1999 and April 2002 at US community health centers located in predominantly Latino underserved areas. INTERVENTIONS: Women randomized to usual care (n = 1805) were discharged immediately after examination. Women randomized to the single-visit group (n = 1716) remained at the clinic until the results of their conventional Papanicolaou test were available. Large loop electrosurgical excision procedure was performed in single-visit patients with either a diagnosis of a high-grade squamous intraepithelial lesion (HGSIL)/atypical glandular cells of undetermined significance (AGUS) or suspicion of carcinoma. All other patients with abnormal Papanicolaou test results were referred to abnormal cytology clinics or elected to receive follow-up care outside the study's medical system. MAIN OUTCOME MEASURES: Treatment rates for HGSIL/AGUS at 6 months, follow-up rates at 6 months for lower-grade lesions, and 1-year follow-up rates for all patients. RESULTS: The rate of abnormal Papanicolaou test results was 4.1%. One percent of results showed high-grade lesions. In the single-visit group, the mean visit time was 2.8 hours and the mean time for delivery and processing of the Papanicolaou tests was 66 minutes. Six months after randomization, 14 (88%) of 16 single-visit and 10 (53%) of 19 usual care patients with HGSIL/AGUS had completed treatment. Fifty percent in the single-visit program and 53% of usual care with less abnormal Papanicolaou tests completed treatment within 6 months. Overall, 36% in each group presented for a follow-up Papanicolaou test 1 year later. Women in the single-visit group with high-grade lesions (10/16; 63%) were significantly more likely to attend follow-up for Papanicolaou tests 12 months later than women with similar lesions in the usual care group (4/19; 21%). CONCLUSIONS: For cervical cancer screening, the single-visit program was feasible and the degree of acceptability was high in this underserved population. Single visit programs provide an opportunity to increase the rate of immediate treatment and follow-up of women with severely abnormal Papanicolaou test results. This strategy did not improve follow-up rates for women with less-abnormal results. Trial Registration http://ClinicalTrials.govIdentifier: NCT00237562.

Adult↗

PubMed2005

Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status.

BACKGROUND: Epidemiologic studies of the association between nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, and breast cancer risk have yielded inconsistent results. We investigated the association of NSAID use with risk of breast cancer in the California Teachers Study cohort, with special attention to risk of specific breast cancer subtypes and to type of NSAID used. METHODS: We analyzed data on 114 460 women in the California Teachers Study cohort who were aged 22 to 85 years and free of breast cancer at baseline in 1995 to 1996. Information on frequency and duration of NSAID use was collected through a self-administered questionnaire. A total of 2391 women were diagnosed with breast cancer during the follow-up period from 1995 to 2001. We used Cox proportional hazards regression to estimate relative risks (RR) and 95% confidence intervals (CI) of breast cancer subtypes with NSAID use. RESULTS: Neither regular use (more than once a week) of any NSAID (aspirin and ibuprofen combined) nor regular use of aspirin was associated with breast cancer risk (RR = 1.09, 95% CI = 0.97 to 1.21 for daily versus no regular use of NSAIDs and RR = 0.98, 95% CI = 0.86 to 1.13 for daily versus no regular use of aspirin). However, long-term (> or = 5 years) daily aspirin users had a non-statistically significant decreased risk of estrogen receptor and progesterone receptor (ER/PR)-positive breast cancer (RR = 0.80, 95% CI = 0.62 to 1.03). In contrast, we observed a statistically significantly increased risk of ER/PR-negative breast cancer with long-term daily use of aspirin (RR = 1.81, 95% CI = 1.12 to 2.92). In this population, 11 fewer ER/PR-positive breast cancer cases and seven excess ER/PR-negative breast cancer cases may be due to daily long-term aspirin use among 2391 breast cancer cases observed over 6 years if the association were proven to be causal. Long-term daily use of ibuprofen was also associated with an increased risk of breast cancer (RR = 1.51, 95% CI = 1.17 to 1.95), particularly of nonlocalized tumors (RR = 1.92, 95% CI = 1.24 to 2.97). If causality were subsequently proven, 16 of the observed 2391 breast cancer cases and 8 of the 713 non-localized breast cancer cases would be attributable to long-term daily use of ibuprofen. CONCLUSIONS: Long-term daily use of NSAIDs was not associated with breast cancer risk overall. Ibuprofen use was associated with an increased risk of breast cancer, and long-term daily aspirin use was associated with an increased risk of ER/PR-negative breast cancer. However, it is not clear if the observed association is causal.

Acetaminophen↗

PubMed2005

Effect of reproductive factors on stage, grade and hormone receptor status in early-onset breast cancer.

INTRODUCTION: Women younger than 35 years who are diagnosed with breast cancer tend to have more advanced stage tumors and poorer prognoses than do older women. Pregnancy is associated with elevated exposure to estrogen, which may influence the progression of breast cancer in young women. The objective of the present study was to examine the relationship between reproductive events and tumor stage, grade, estrogen receptor and progesterone receptor status, and survival in women diagnosed with early-onset breast cancer. METHODS: In a population-based, case-case study of 254 women diagnosed with invasive breast cancer at age under 35 years, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression with tumor characteristics as dependent variables and adjusting for age and education. Survival analyses also examined the relationship between reproductive events and overall survival. RESULTS: Compared with nulliparous women, women with three or more childbirths were more likely to be diagnosed with nonlocalized tumors (OR = 3.1, 95% CI = 1.3-7.7), and early age (<20 years) at first full-term pregnancy was also associated with a diagnosis of breast cancer that was nonlocalized (OR = 3.0, 95% CI = 1.2-7.4) and of higher grade (OR = 3.2, 95% CI 1.0-9.9). The hazard ratio for death among women with two or more full-term pregnancies, as compared with those with one full-term pregnancy or none, was 2.1 (95% CI = 1.0-4.5), adjusting for stage. Among parous women, those who lactated were at decreased risk for both estrogen receptor and progesterone receptor negative tumors (OR = 0.2, 95% CI = 0.1-0.5, and OR = 0.4, 95% CI = 0.2-0.8, respectively). CONCLUSION: The results of the present study suggest that pregnancy and lactation may influence tumor presentation and survival in women with early-onset breast cancer.

Adult↗

PubMed2005

Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X.

CONTEXT: Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown. OBJECTIVE: To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities. DESIGN, SETTING, AND PARTICIPANTS: Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses. MAIN OUTCOME MEASURES: Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data. RESULTS: Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001). CONCLUSIONS: Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of "familial colorectal cancer type X" is suggested to describe this type of familial aggregation of colorectal cancer.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types.

STK15 (Aurora-A) is a serine/threonine kinase involved in mitotic chromosomal segregation. A genetic variant in STK15 T+91A (resulting in the amino acid substitution F31I) is associated with increased aneuploidy in colon tumors and cell transformation in vitro. Since this polymorphism plays a role in mitotic control-a process critical for all cancer types-we conducted association analyses for risk of cancer development of the colon, breast, prostate, skin, lung and esophagus in 10 independent case-control populations. We carried out a meta-analysis of these 10 case-control studies together with 5 additional published studies for a total of 9549 cases of breast, colon, ovarian, prostate, lung, esophageal and non-melanoma skin cancer and 8326 population or hospital-based controls. Meta-analysis of three colorectal cancer studies showed an increased risk in T+91A homozygotes (OR=1.50; 95% CI of 1.14-1.99). Meta-analysis of four breast cancer studies showed increased risk for T+91A homozygotes (OR=1.35, 95% CI of 1.12-1.64). The results of the multiple cancer type meta-analysis for all 15 studies combined were significant for cancer risk in both homozygotes and heterozygotes. The T+91A heterozygotes show an OR of 1.10 (95% CI of 1.03-1.18, P-value=0.006) and the T+91A homozygotes show an OR of 1.40 (95% CI of 1.22-1.59, P-value<0.001) for cancer risk. These results confirm that the STK15 T+91A variant is a low penetrance cancer susceptibility allele affecting multiple cancer types, and provide genetic evidence from large-scale human population studies that genetic stability at the chromosome level is an important determinant of cancer susceptibility. The data also underline the advantages of comparative association studies involving study populations from different ethnic groups for determination of disease risk.

Animals↗

PubMed2005

Residential mobility in the California Teachers Study: implications for geographic differences in disease rates.

BACKGROUND: Especially for cancers with long latency periods, such as breast cancer, the issue of residential mobility hinders ecologic analyses seeking to examine the role of environmental contaminants in chronic disease etiology. This study describes and evaluates characteristics associated with residential mobility in a sub-sample of the California Teachers Study (CTS) cohort. METHODS: In 2000, lifetime residential histories were collected for a sub-sample of 328 women enrolled in the CTS; women's degree of residential mobility and associated factors were analyzed. RESULTS: While most women moved many times during their lives (average = 8.9), the average number of years at their residence when they enrolled in the study was reasonably long (15.1 years). Age strongly predicted duration at current residence but was not related to the number of lifetime residences. After adjusting for age, California-born women and women living in high socioeconomic status (SES) neighborhoods were significantly more residentially stable. Agreement between self-reported urbanization of recent residences and that based on census data of the geocoded residences was very good (80% concordant). Among women currently living in urban areas, an average of 43.3 years, or 77%, of their lifetimes were spent in urban residences; among women currently living in a rural area, an average of 37.3 years, or 67% of their lifetimes were spent in rural residences. CONCLUSIONS: This suggests that analyses of incidence rates based on current residence, while not capturing a woman's full exposure history, may reasonably reflect some aspect of longer term chronic exposures, especially those related to urbanization, at least in professional women.

Adult↗

PubMed2005

R5 human immunodeficiency virus type 1 infection of fetal thymic organ culture induces cytokine and CCR5 expression.

Late-stage CCR5 tropic human immunodeficiency virus type 1 (HIV-1) isolates (R5 HIV-1) can deplete nearly all CD4+ thymocytes from human thymus/liver grafts, despite the fact that fewer than 5% of these cells express CCR5. To resolve this paradox, we studied the replication and cytopathic effects (CPE) of late-stage R5 HIV-1 biological clones from two progressors and two long-term nonprogressors (LTNP) in fetal thymic organ culture (FTOC) with and without added cytokines. We found that R5 HIV-1 clones from progressors but not LTNP were cytopathic in untreated FTOC. Moreover, R5 HIV-1 clones from progressors replicated to higher levels than LTNP-derived R5 HIV-1 clones in this system. In contrast, when FTOC was maintained in the presence of interleukin 2 (IL-2), IL-4, and IL-7, both progressor and LTNP clones exhibited similar replication and CPE, which were equal to or greater than the levels achieved by progressor-derived R5 HIV-1 clones in untreated FTOC. This finding was likely due to IL-2-induced CCR5 expression on CD4+ thymocytes in FTOC. R5 HIV-1 clones showed greater pathogenesis for CCR5+ cells but also showed evidence of CPE on CCR5- cells. Furthermore, infection of FTOC by R5 HIV-1 induced IL-10 and transforming growth factor beta (TGF-beta) expression. Both IL-10 and TGF-beta in turn induced CCR5 expression in FTOC. Induction of CCR5 expression via cytokine induction by R5 HIV-1 infection of CCR5+ thymocytes likely permitted further viral replication in newly CCR5+ thymocytes. CCR5 expression, therefore, is a key determinant of pathogenesis of R5 HIV-1 in FTOC.

Cytokines↗

PubMed2005

Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations.

BACKGROUND: Recent oral contraceptive use has been associated with a small increase in breast cancer risk and a substantial decrease in ovarian cancer risk. The effects on risks for women with germ line mutations in BRCA1 or BRCA2 are unclear. METHODS: Subjects were population-based samples of Caucasian women that comprised 1,156 incident cases of invasive breast cancer diagnosed before age 40 (including 47 BRCA1 and 36 BRCA2 mutation carriers) and 815 controls from the San Francisco Bay area, California, Ontario, Canada, and Melbourne and Sydney, Australia. Relative risks by carrier status were estimated using unconditional logistic regression, comparing oral contraceptive use in case groups defined by mutation status with that in controls. RESULTS: After adjustment for potential confounders, oral contraceptive use for at least 12 months was associated with decreased breast cancer risk for BRCA1 mutation carriers [odds ratio (OR), 0.22; 95% confidence interval (CI), 0.10-0.49; P < 0.001], but not for BRCA2 mutation carriers (OR, 1.02; 95% CI, 0.34-3.09) or noncarriers (OR, 0.93; 95% CI, 0.69-1.24). First use during or before 1975 was associated with increased risk for noncarriers (OR, 1.52 per year of use before 1976; 95% CI, 1.22-1.91; P < 0.001). CONCLUSIONS: There was no evidence that use of current low-dose oral contraceptive formulations increases risk of early-onset breast cancer for mutation carriers, and there may be a reduced risk for BRCA1 mutation carriers. Because current formulations of oral contraceptives may reduce, or at least not exacerbate, ovarian cancer risk for mutation carriers, they should not be contraindicated for a woman with a germ line mutation in BRCA1 or BRCA2.

Adult↗

PubMed2004

The Breast Cancer Family Registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer.

INTRODUCTION: The etiology of familial breast cancer is complex and involves genetic and environmental factors such as hormonal and lifestyle factors. Understanding familial aggregation is a key to understanding the causes of breast cancer and to facilitating the development of effective prevention and therapy. To address urgent research questions and to expedite the translation of research results to the clinical setting, the National Cancer Institute (USA) supported in 1995 the establishment of a novel research infrastructure, the Breast Cancer Family Registry, a collaboration of six academic and research institutions and their medical affiliates in the USA, Canada, and Australia. METHODS: The sites have developed core family history and epidemiology questionnaires, data dictionaries, and common protocols for biospecimen collection and processing and pathology review. An Informatics Center has been established to collate, manage, and distribute core data. RESULTS: As of September 2003, 9116 population-based and 2834 clinic-based families have been enrolled, including 2346 families from minority populations. Epidemiology questionnaire data are available for 6779 affected probands (with a personal history of breast cancer), 4116 unaffected probands, and 16,526 relatives with or without a personal history of breast or ovarian cancer. The biospecimen repository contains blood or mouthwash samples for 6316 affected probands, 2966 unaffected probands, and 10,763 relatives, and tumor tissue samples for 4293 individuals. CONCLUSION: This resource is available to internal and external researchers for collaborative, interdisciplinary, and translational studies of the genetic epidemiology of breast cancer. Detailed information can be found at the URL http://www.cfr.epi.uci.edu/.

Age Distribution↗

PubMed2004

Active smoking, household passive smoking, and breast cancer: evidence from the California Teachers Study.

BACKGROUND: There is great interest in whether exposure to tobacco smoke, a substance containing human carcinogens, may contribute to a woman's risk of developing breast cancer. To date, literature addressing this question has been mixed, and the question has seldom been examined in large prospective study designs. METHODS: In a 1995 baseline survey, 116 544 members of the California Teachers Study (CTS) cohort, with no previous breast cancer diagnosis and living in the state at initial contact, reported their smoking status. From entry into the cohort through 2000, 2005 study participants were newly diagnosed with invasive breast cancer. We estimated hazard ratios (HRs) for breast cancer associated with several active smoking and household passive smoking variables using Cox proportional hazards models. RESULTS: Irrespective of whether we included passive smokers in the reference category, the incidence of breast cancer among current smokers was higher than that among never smokers (HR = 1.32, 95% confidence interval [CI] = 1.10 to 1.57 relative to all never smokers; HR = 1.25, 95% CI = 1.02 to 1.53 relative to only those never smokers who were unexposed to household passive smoking). Among active smokers, breast cancer risks were statistically significantly increased, compared with all never smokers, among women who started smoking at a younger age, who began smoking at least 5 years before their first full-term pregnancy, or who had longer duration or greater intensity of smoking. Current smoking was associated with increased breast cancer risk relative to all nonsmokers in women without a family history of breast cancer but not among women with such a family history. Breast cancer risks among never smokers reporting household passive smoking exposure were not greater than those among never smokers reporting no such exposure. CONCLUSION: Our study provides evidence that active smoking may play a role in breast cancer etiology and suggests that further research into the connection is warranted, especially with respect to genetic susceptibilities.

Adult↗

PubMed2004

Residential proximity to agricultural pesticide use and incidence of breast cancer in the California Teachers Study cohort.

We examined the association between residential proximity to agricultural pesticide use and breast cancer incidence among members of the California Teachers Study cohort, a large study of professional school employees with extensive information on breast cancer risk factors, followed for cancer incidence since 1995. We identified 1552 invasive breast cancer cases, diagnosed between 1996 and 1999, among 114,835 cohort members. We used California Pesticide Use Reporting data to select pesticides for analysis based on use volume, carcinogenic potential, and exposure potential; a Geographic Information System was used to estimate pesticide applications within a half-mile radius of subjects' residences. We applied Cox proportional hazard models to estimate hazard rate ratios (HR) for selected pesticides, adjusting for age, race, and socioeconomic status. We saw no association between residential proximity to recent agricultural pesticide use and invasive breast cancer incidence. HR estimates for the highest compared to the lowest exposure categories for groups of agents were as follows: probable or likely carcinogens (1.07, 95% confidence interval (CI): 0.86-1.32), possible or suggestive carcinogens (1.06, 95% CI: 0.87-1.29), mammary carcinogens (1.15, 95% CI: 0.90-1.48), and endocrine disruptors (1.03, 95% CI: 0.86-1.25). HR estimates for other groups and individual pesticides did not differ from unity, nor was there a trend for any groupings of or individual pesticides examined. Stratifying by menopausal status or family history of breast cancer did not substantially affect our results. Our analyses suggest that breast cancer incidence is not elevated in areas of recent, high agricultural pesticide use in California.

Adult↗