Individual Cancer Types Research Articles

Cancer Burden in the HIV-Infected Population in the United States

Effective antiretroviral therapy has reduced the risk of AIDS and dramatically prolonged the survival of HIV-infected people in the United States. Consequently, an increasing number of HIV-infected people are at risk of non-AIDS-defining cancers that typically occur at older ages. We estimated the annual number of cancers in the HIV-infected population, both with and without AIDS, in the United States. Incidence rates for individual cancer types were obtained from the HIV/AIDS Cancer Match Study by linking 15 HIV and cancer registries in the United States. Estimated counts of the US HIV-infected and AIDS populations were obtained from Centers for Disease Control and Prevention surveillance data. We obtained estimated counts of AIDS-defining (ie, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers in the US AIDS population during 1991-2005 by multiplying cancer incidence rates and AIDS population counts, stratified by year, age, sex, race and ethnicity, transmission category, and AIDS-relative time. We tested trends in counts and standardized incidence rates using linear regression models. We multiplied overall cancer rates and HIV-only (HIV infected, without AIDS) population counts, available from 34 US states during 2004-2007, to estimate cancers in the HIV-only population. All statistical tests were two-sided. The US AIDS population expanded fourfold from 1991 to 2005 (96,179 to 413,080) largely because of an increase in the number of people aged 40 years or older. During 1991-2005, an estimated 79 656 cancers occurred in the AIDS population. From 1991-1995 to 2001-2005, the estimated number of AIDS-defining cancers decreased by greater than threefold (34,587 to 10,325 cancers; P(trend) < .001), whereas non-AIDS-defining cancers increased by approximately threefold (3193 to 10,059 cancers; P(trend) < .001). From 1991-1995 to 2001-2005, estimated counts increased for anal (206 to 1564 cancers), liver (116 to 583 cancers), prostate (87 to 759 cancers), and lung cancers (875 to 1882 cancers), and Hodgkin lymphoma (426 to 897 cancers). In the HIV-only population in 34 US states, an estimated 2191 non-AIDS-defining cancers occurred during 2004-2007, including 454 lung, 166 breast, and 154 anal cancers. Over a 15-year period (1991-2005), increases in non-AIDS-defining cancers were mainly driven by growth and aging of the AIDS population. This growing burden requires targeted cancer prevention and treatment strategies.

Improving progression-free and overall survival in patients with cancer: a potential role for bisphosphonates

Introduction: Bisphosphonates are a well-established therapy for patients with multiple myeloma or bone metastases from advanced cancers and are used routinely to delay the onset and reduce the risk of skeletal-related events. Emerging evidence indicates that they also may provide additional anticancer benefits. These developments warrant reappraisal of their role in patients with cancer and reevaluation of optimal therapeutic regimens.Areas covered: This article reviews the evidence of the anticancer activity of bisphosphonates in patients with solid tumors or multiple myeloma. The underlying mechanisms of the anticancer activity of bisphosphonates are elucidated from preclinical and translational data that show that bisphosphonates suppress tumor growth and survival, inhibit tumor-mediated angiogenesis, or stimulate host anticancer immune response. These data also provide insights into the potential for therapeutic combinations. Preclinical and clinical data relating to the anticancer effects of bisphosphonates are reviewed by cancer type.Expert opinion: Future trials of bisphosphonates in cancer patients will explore the underlying mechanism of the anticancer benefit in greater detail and attempt to examine critically the potential clinical benefit in individual cancer types in early/advanced disease.

Cancer Cluster Investigation in Residents Near a Municipal Landfill

ABSTRACT While there are several studies of the health status of residents near hazardous waste landfills, relatively few have focused on the health of individuals living near municipal landfills. We assessed whether there were increased incidence rates of 18 cancer types and all cancers combined among residents near the Northampton Regional Landfill in western Massachusetts by conducting analyses for the cities of Northampton and Easthampton, as well as each census tract in these cities, between years 1982 and 2004. We also examined incidence rates within a 1-mile radius of the landfill and examined spatial patterns of all cancer cases in Northampton and Easthampton. The majority of cancer types occurred at, near, or below expected rates. No statistically significant association persisted over time. Within 1 mile of the landfill, all cancers combined occurred at rates comparable to the statewide average (SIR = 94, 95% CI: 69, 120) from 1997 to 2004, as did all individual cancer types analyzed. There were no unusual spatial patterns of cases in the area surrounding the landfill for the entire study period or four individual periods examined. The results do not support the hypothesis that residing near the investigated municipal landfill was associated with increased cancer risk.

Representation of Cancer in the Medical Literature - A Bibliometric Analysis

BackgroundThere exists a lack of knowledge regarding the quantity and quality of scientific yield in relation to individual cancer types. We aimed to measure the proportion, quality and relevance of oncology-related articles, and to relate this output to their associated disease burden. By incorporating the impact factor(IF) and Eigenfactor™(EF) into our analysis we also assessed the relationship between these indices and the output under study.MethodsAll publications in 2007 were retrieved for the 26 most common cancers. The top 20 journals ranked by IF and EF in general medicine and oncology, and the presence of each malignancy within these titles was analysed. Journals publishing most prolifically on each cancer were identified and their impact assessed.Principal Findings63260 (PubMed) and 126845 (WoS) entries were generated, respectively. 26 neoplasms accounted for 25% of total output from the top medical publications. 5 cancers dominated the first quartile of output in the top oncology journals; breast, prostate, lung, and intestinal cancer, and leukaemia. Journals associated with these cancers were associated with much higher IFs and EFs than those journals associated with the other cancer types under study, although these measures were not equivalent across all sub-specialties. In addition, yield on each cancer was related to its disease burden as measured by its incidence and prevalence.ConclusionsOncology enjoys disproportionate representation in the more prestigious medical journals. 5 cancers dominate yield, although this attention is justified given their associated disease burden. The commonly used IF and the recently introduced EF do not correlate in the assessment of the preeminent oncology journals, nor at the level of individual malignancies; there is a need to delineate between proxy measures of quality and the relevance of output when assessing its merit. These results raise significant questions regarding the best method of assessment of research and scientific output in the field of oncology.

ERG rearrangement is specific to prostate cancer and does not occur in any other common tumor

Identification of specific somatic gene alterations is crucial for the insight into the development, progression, and clinical behavior of individual cancer types. The recently discovered recurrent ERG rearrangement in prostate cancer might represent a prostate cancer-specific alteration that has not been systematically assessed in tumors other than prostate cancer. Aim of this study was to assess, whether the ERG rearrangement and the distinct deletion site between TMPRSS2 and ERG, both predominantly resulting in a TMPRSS2–ERG fusion, occur in tumors other than prostate cancer. We assessed 54 different tumor types (2942 samples in total) for their ERG rearrangement status by fluorescence in situ hybridization (FISH). To calibrate, we analyzed 285 prostate cancer samples for the ERG rearrangement frequency. Additionally, we interrogated a high-resolution single nucleotide polymorphism (SNP) data set across 3131 cancer specimens (26 tumor types) for copy number alterations. None of the 54 different tumor types assessed by FISH harbored an ERG rearrangement, whereas the prostate cancer samples revealed an ERG rearrangement in 49.5% of cases. Furthermore, within the 26 tumor types assessed for copy number alterations by SNP, the distinct deletion site between TMPRSS2 and ERG (21q22.2–3) was detectable exclusively in prostate cancer. Although Ewing's sarcoma and AML have known rearrangements rarely involving ERG, we hypothesize that the ERG rearrangement as well as the distinct deletion site on 21q22.2–3 between TMPRSS2 and ERG are prostate-cancer-specific genomic alterations. These observations provide further insight into the oncogenesis of prostate cancer and might be critical for the development of ERG rearrangement assessment as a clinical tool.

Abstract 5759: The landscape of copy-number changes across multiple human cancer types

Abstract Genomic regions undergoing frequent alteration in human cancers often point to genes that play causal roles in oncogenesis. We have performed high-resolution analyses of copy-number alterations from 3131 cancer specimens across multiple histological types. We identified 158 regions of that are significantly altered by focal copy-number changes. Among these, 122 regions cannot be explained by the presence of a known cancer gene. Several gene families are enriched among these regions, including the BCL2 family of apoptosis regulators and the NF-κB pathway. Cell lines with amplifications of the anti-apoptotic genes MCL1 and BCL2L1 depend upon these genes for survival. Finally, we find that the majority of copy-number changes identified in individual cancer types are present across multiple cancer types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5759.

Risk of Extra-Intestinal Cancer in Inflammatory Bowel Disease: Meta-Analysis of Population-Based Cohort Studies

Extra-intestinal manifestations of inflammatory bowel disease (IBD) are relatively common, whereas the risk of extra-intestinal cancer (EIC) remains uncertain. The aim of this study was to obtain a reliable estimate of the risk of EIC in Crohn's disease (CD) and ulcerative colitis (UC) by performing a meta-analysis of population-based cohort studies. A systematic literature review was performed using MEDLINE (1966-2009) and abstracts from recent international conferences. Eight population-based cohort studies comprising a total of 17,052 patients with IBD were available. Standardized incidence ratios (SIRs) of EICs were pooled in a meta-analysis approach using STATA software. Overall, IBD patients were not at increased risk of EIC (SIR, 1.10; 95% confidence interval (CI) 0.96-1.27). However, site-specific analyses revealed that CD patients had an increased risk of cancer of the upper gastrointestinal tract (SIR 2.87, 95% CI 1.66-4.96), lung (SIR 1.82, 95% CI 1.18-2.81), urinary bladder (SIR 2.03, 95% CI 1.14-3.63), and skin (SIR 2.35, 95% CI 1.43-3.86). Patients with UC had a significantly increased risk of liver-biliary cancer (SIR 2.58, 95% CI 1.58-4.22) and leukemia (SIR 2.00, 95% CI 1.31-3.06) but a decreased risk of pulmonary cancer (SIR 0.39, 95% CI 0.20-0.74). Although the overall risk of EIC was not significantly increased among patients with IBD, the risk of individual cancer types differed from that of the background population as well as between CD and UC patients. These findings may primarily be explained by smoking habits, extra-intestinal manifestations of IBD, and involvement of the upper gastrointestinal tract in CD.

The landscape of somatic copy-number alteration across human cancers

A powerful way to discover key genes playing causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here, we report high-resolution analyses of somatic copy-number alterations (SCNAs) from 3131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across multiple cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-κB pathway. We show that cancer cells harboring amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend upon expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in multiple cancer types.

Gene expression in colorectal neoplasia: modifications induced by tissue ischaemic time and tissue handling protocol

The heterogeneity within individual distinct cancer types in terms of behaviour, response to therapy and prognosis is well recognized. A major goal of translational research projects has therefore been to define clinically significant subgroups of individual tumour types by analysis of mRNA as well as protein expression. An essential premise of such investigations is that expression of these key molecules is a true reflection of conditions present within the neoplastic cells in vivo. The aim was to investigate the effect of methods of tissue handling and storage on expression of mRNA. mRNA expression in 60 biopsy samples obtained from 10 patients with colorectal tumours was examined. The mRNA expression profile and the level of expression of specific mRNA species were significantly affected by the procedures used for collection and storage of tissue samples. Significant variation in the level of expression (both increased and decreased) of transcripts was detectable after 15 min, and by 120 min there was a fourfold increase in the number of genes with a more than twofold change in the level of expression. Reliable interpretation of results of gene expression at the mRNA level requires standardized protocols for tissue procurement.

Trends in the incidence of cancers among HIV-infected persons and the impact of antiretroviral therapy: authors' reply

Trends in the incidence of cancers among HIV-infected persons and the impact of antiretroviral therapy: authors' reply

Cancer aggressiveness and mortality in men of exceptional age

11051 Background: Information on the characteristics of cancer in people ≥ 85 is limited, particularly in men. Methods: We evaluated the type, grade and extent of cancer among the 22,071 men in the Physicians’ Health Study by age at diagnosis (dx) (&lt;65, 65–74, 75–84 and ≥85). All cases of cancer, deaths and cause of death were confirmed by medical record review. To investigate the relationship between age at dx and risk of cancer death, we matched newly diagnosed cancer patients to reference subjects by age and a modified Charlson comorbidity score. Participants were followed for all cause mortality. We estimated hazard ratios (HR) for death by age at dx using Cox proportional hazards models and adjusted for potential confounders. Results: Over a mean follow-up of 20.5 years, 5,623 incident cancers were confirmed. Prostate cancer remained the most common cancer across all age groups. Melanoma and lung cancer became less common with age, while unknown cancers and gastrointestinal cancers other than colorectal (other GI) became more common. There was no linear trend toward higher or lower grade across the four age groups for individual cancer types. For men ≥ 85 the frequency of metastatic cancer at dx increased for prostate (5.8% vs 14.6% p=0.01) and decreased for other GI tumors (63.8% vs 43.5% p=0.05). Cancer as a cause of death decreased among the entire cohort from 44.1% in men aged 55–64 to 20.5% in men ≥ 85, and among those with cancer it decreased from 93.6% to 52.8%. In the matched cohort analysis, the HR for death from all cancers combined declined markedly across categories of increasing age at cancer dx from 10.9 (95%CI:6.0–19.9) in men &lt; 55 to 1.9 (95%CI:1.5–2.4) in men ≥ 85. There was a similar decline in the HR with increasing age for cancer death from lymphoma, melanoma, prostate and colorectal cancers, whereas the HR of lung, other GI and urinary tumors remained stable. Conclusions: In this prospective cohort of apparently healthy U.S. male physicians, characteristics of cancer in men ≥ 85 varied considerably with tumor type and may reflect changes in cancer detection or biology with age. Cancer specific mortality decreased markedly with increasing age of diagnosis for most cancers. This is likely explained by competing risks of death which outpace that of cancer, but may also suggest decreased cancer aggressiveness in advanced age. No significant financial relationships to disclose.

A Field Synopsis on Low-Penetrance Variants in DNA Repair Genes and Cancer Susceptibility

Several genes encoding for DNA repair molecules implicated in maintaining genomic integrity have been proposed as cancer-susceptibility genes. Although efforts have been made to create synopses for specific fields that summarize the data from genetic association studies, such an overview is not available for genes involved in DNA repair. We have created a regularly updated database of studies addressing associations between DNA repair gene variants (excluding highly penetrant mutations) and different types of cancer. Using 1087 datasets and publicly available data from genome-wide association platforms, meta-analyses using dominant and recessive models were performed on 241 associations between individual variants and specific cancer types that had been tested in two or more independent studies. The epidemiological strength of each association was graded with Venice criteria that assess amount of evidence, replication, and protection from bias. All statistical tests were two-sided. Thirty-one nominally statistically significant (ie, P < .05 without adjustment for multiple comparisons) associations were recorded for 16 genes in dominant and/or recessive model analyses (BRCA2, CCND1, ERCC1, ERCC2, ERCC4, ERCC5, MGMT, NBN, PARP1, POLI, TP53, XPA, XRCC1, XRCC2, XRCC3, and XRCC4). XRCC1, XRCC2, TP53, and ERCC2 variants were each nominally associated with several types of cancer. Three associations were graded as having "strong" credibility, another four had modest credibility, and 24 had weak credibility based on Venice criteria. Requiring more stringent P values to account for multiplicity of comparisons, only the associations of ERCC2 codon 751 (recessive model) and of XRCC1 -77 T>C (dominant model) with lung cancer had P <or= .0001 and retained P <or= .001 even when the first published studies on the respective associations were excluded. We have conducted meta-analyses of 241 associations between variants in DNA repair genes and cancer and have found sparse association signals with strong epidemiological credibility. This synopsis offers a model to survey the current status and gaps in evidence in the field of DNA repair genes and cancer susceptibility, may indicate potential pleiotropic activity of genes and gene pathways, and may offer mechanistic insights in carcinogenesis.

Academic clinical trials in the 21st century – where do we go from here? The research approach of the Arbeitsgemeinschaft Medikamentöse Tumortherapie (AGMT)

Advances in the fields of cellular, molecular biology and immunobiology are opening a wide range of diagnostic and therapeutic approaches towards optimally tailored management of cancer patients. The ever-increasing armamentarium of the state-of-the-art molecular, genetic and immunological tools for the diagnosis, risk determination, treatment stratification and molecular follow-up of individual cancer types results in high challenges for knowledge and experience of medical oncologists and their need for cooperation with other disciplines in a fine-tuned network of specialists. Within this background the Arbeitsgemeinschaft medikamentose Tumortherapie ("AGMT") has been founded as an academic study group focussed on enabling a series of aims for participating study groups: (i) to maintain and improve the possibility to carry out innovative investigator-initiated trials in medical oncology and haematology, (ii) to give guidance to clinicians and allow patients' access to modern treatment options in rapidly developing fields of cancer therapy, (iii) to allow highly innovative phase I and II treatment approaches, (iv) to make the access to industry-sponsored trials easier and (v) to facilitate cooperation between medical oncologists and other specialists involved in the care of cancer patients. Meanwhile in 20 years of activity in the field of oncologic clinical research, a number of academic clinical trials have been successfully conducted, leading to both publications in peer-reviewed journals and presentations at major international conferences. During the last two years, the AGMT has set out to significantly increase its research portfolio with studies in solid cancers and haematology, while at the same time accomodating changes in the regulatory environment and increased responsibilities for sponsors of academic clinical trials arising from the implementation of the EU Clinical Trial Directive into national legislation.

A Potent Anti-Carcinoma and Anti-Acute Myeloblastic Leukemia Agent, AG490

Proteins with tyrosine kinase activity are recognized as key regulators of cellular processes including growth and differentiation. Tyrosine kinase receptors e.g. EGFR and soluble tyrosine kinase proteins e.g. JAK-2, have emerged as essentials in cell survival for cervical carcinoma and acute myeloblastic leukemia, respectively. These receptors and soluble cytoplasm networks have been studied in detail and finally pharmacological agents, targeted at key molecules, could be produced. Tyrphostins are kinases inhibitors synthesized on the basic structure of erbstatin a natural kinase inhibitor. The JAK-2 specific inhibitor, Tyrphostin AG490 is used to inhibit phosphorylation of EGFR and signal transducer and activator of transcription 3 [STAT-3], and subsequently reduce invasion and adhesion potential of malignant cells. This review summarizes experiments providing a detailed picture of how hematopoietic cancer c-Kit+, Jak-2+ and non hematopoietic tumors c-Kit+, HER-2+, JAK-2+ can be inhibited by the chemosensitizing agent AG490 causing programmed cell death. Furthermore, studies presented herein analyzed several cellular targets that can be modified by the same death effector. The highly conserved JAK-2/STAT-3, c-Kit, and HER-2 signaling pathways play pleiotropic roles during embryonic development and are important for the regulation of self-renewing tissues. The physiological functions of these signaling cascades range from stem cell maintenance and influencing cell fate decisions of progenitor cells, to the induction of terminal differentiation processes, all of which have been found to be recapitulated in different forms of cancers. Inhibiting their action by AG490 represents a therapeutic approach for the treatment of individual types of cancer and several broad-spectrum.

Cancer incidence in relatives of British Fanconi Anaemia patients

BackgroundFanconi anemia (FA) is an autosomal recessive DNA repair disorder with affected individuals having a high risk of developing acute myeloid leukaemia and certain solid tumours. Thirteen complementation groups have been identified and the genes for all of these are known (FANCA, B, C, D1/BRCA2, D2, E, F, G, I, J/BRIP1, L, M and N/PALB2). Previous studies of cancer incidence in relatives of Fanconi anemia cases have produced conflicting results. A study of British FA families was therefore carried out to investigate this question, since increases in cancer risk in FA heterozygotes would have implications for counselling FA family members, and possibly also for the implementation of preventative screening measures in FA heterozygotes.MethodsThirty-six families took part and data was collected on 575 individuals (276 males, 299 females), representing 18,136 person years. In this cohort, 25 males and 30 females were reported with cancer under the age of 85 years, and 36 cancers (65%) could be confirmed from death certificates, cancer registries or clinical records.ResultsA total of 55 cancers were reported in the FA families compared to an estimated incidence of 56.95 in a comparable general population cohort, and the relative risk of cancer was 0.97 (95% C.I. = 0.71–1.23, p = 0.62) for FA family members. Analysis of relative risk for individual cancer types in each carrier probability group did not reveal any significant differences with the possible exception of prostate cancer (RR = 3.089 (95% C.I. = 1.09 – 8.78; Χ2 = 4.767, p = 0.029).ConclusionThis study has not shown a significant difference in overall cancer risk in FA families.

The distinctive biology of cancer in adolescents and young adults

One explanation for the relative lack of progress in treating cancer in adolescents and young adults is that the biology of malignant diseases in this age group is different than in younger and older persons, not only in the spectrum of cancers but also within individual cancer types and within the patient (host). Molecular, epidemiological and therapeutic outcome comparisons offer clues to this distinctiveness in most of the common cancers of adolescents and young adults. Translational and clinical research should not assume that the biology of cancers and patients is the same as in other age groups, and treatment strategies should be tailored to the differences.

Statins and Cancer Risk

Statins are cholesterol-lowering drugs that have been proven in randomized controlled trials to prevent cardiac events. Recent retrospective analyses have suggested that statins also prevent cancer. To investigate the effect of statin therapy on cancer incidence and cancer death and to analyze the effect of statins on specific cancers and the effect of statin lipophilicity or derivation. A systematic literature search of MEDLINE, EMBASE, CINAHL, Web of Science, CANCERLIT, and the Cochrane Systematic Review Database through July 2005 was conducted using specific search terms. A review of cardiology and cancer abstracts and manual review of references was also performed. Twenty-seven of the 8943 articles (n = 86,936 participants) initially identified met the inclusion criteria, reporting 26 randomized controlled trials of statins, with a mean duration of follow-up of at least 1 year, enrolling a minimum of 100 patients, and reporting data on either cancer incidence (n = 20 studies) or cancer death (n = 22 studies). All data were independently extracted by 3 investigators using a standardized data abstraction tool. Weighted averages were reported as odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model (DerSimonian and Laird methods). Statistical heterogeneity scores were assessed with the Q statistic. In meta-analyses including 6662 incident cancers and 2407 cancer deaths, statins did not reduce the incidence of cancer (OR, 1.02; 95% CI, 0.97-1.07) or cancer deaths (OR, 1.01; 95% CI, 0.93-1.09). No reductions were noted for any individual cancer type. This null effect on cancer incidence persisted when only hydrophilic, lipophilic, naturally derived, or synthetically derived statins were evaluated. Statins have a neutral effect on cancer and cancer death risk in randomized controlled trials. We found that no type of cancer was affected by statin use and no subtype of statin affected the risk of cancer.

Expression and functional analysis of Bax inhibitor‐1 in human breast cancer cells

Recently, deregulated expression of the anti-apoptotic protein Bax inhibitor-1 (BI-1) has been shown in several human cancers. In this report, we show that BI-1 is expressed at various levels in six different human breast cancer cell lines. In order to investigate the function of BI-1 in oestrogen-dependent MCF-7, T-47D and oestrogen-independent MDA-MB-231 breast cancer cells, the RNA interference technique was used to knock down BI-1 expression specifically. Suppression of BI-1 expression caused a significant increase in spontaneous apoptosis in MDA-MB-231 cells, whereas MCF-7 and T-47D cells remained almost unaffected. Furthermore, BI-1 expression analysis using a cancer profiling array showed up-regulation of BI-1 expression in cancer samples of breast, uterus and ovary, whereas down-regulated BI-1 expression was identified in stomach, colon, kidney, lung and rectal cancer. In addition, immunohistochemical studies using a BI-1-specific antibody on human breast cancer specimens also revealed that BI-1 is expressed in the majority of cases. Moreover, to analyse whether BI-1 expression is oestrogen receptor-dependent, tumour cells were treated with oestradiol, ICI and tamoxifen: this showed no significant changes in BI-1 expression. Taken together, our results demonstrate that BI-1 expression is differentially deregulated in different cancers and that BI-1 plays an important role in preventing certain breast cancer cells from undergoing apoptosis. Thus, the development of novel therapeutic strategies based on targeting BI-1 gene expression in breast cancer could be restricted to selected individual cancer types.

Breast-Feeding and Cancer: The Boyd Orr Cohort and a Systematic Review With Meta-Analysis

Having been breast-fed has been suggested to influence cancer risk in adulthood. We investigated associations between breast-feeding during infancy and adult cancer incidence and mortality in a cohort study and meta-analyses of published studies. The Boyd Orr cohort consisted of 4999 subjects who were originally surveyed in 1937-39, when they were 0-19 years of age. Cancer outcomes from 1948 through 2003 were available for 4379 (88%) subjects, and 3844 had complete data on all covariates. Associations of breast-feeding with cancer were investigated using proportional hazards models. We also identified 14 studies on infant feeding and cancer published from 1966 through July 2005, of which 10 could be combined with the Boyd Orr cohort results in a meta-analysis of breast cancer using random-effect models. In the Boyd Orr cohort, ever having been breast-fed, compared with never having been breast-fed, was not associated with the incidence of all cancers (hazard ratio [HR] = 1.07, 95% confidence interval [CI] = 0.89 to 1.28) or of any individual cancer type examined (prostate HR = 1.43, 95% CI = 0.58 to 3.52; breast HR = 1.62, 95% CI = 0.89 to 2.94; colorectal HR = 0.86, 95% CI = 0.45 to 1.63; gastric HR = 1.22, 95% CI = 0.47 to 3.15). In the meta-analysis, there was also no association between breast-feeding and breast cancer (regardless of menopausal status) (relative risk [RR] = 0.94, 95% CI = 0.85 to 1.04). However, breast-fed women had a reduced risk of premenopausal breast cancer (RR = 0.88, 95% CI = 0.79 to 0.98) but not of postmenopausal breast cancer (RR = 1.00, 95% CI = 0.86 to 1.16). Ever having been breast-fed was not associated with overall breast cancer risk, although the meta-analysis revealed a reduced risk of premenopausal breast cancer in women who had been breast-fed.

4-Aminobiphenyl-Hemoglobin Adducts and Risk of Smoking-Related Disease in Never Smokers and Former Smokers in the European Prospective Investigation into Cancer and Nutrition Prospective Study

The aim of this study was to evaluate whether biomarkers of environmental tobacco smoke exposure [i.e., 4-aminobiphenyl-hemoglobin (4-ABP-Hb) adducts] were predictive of the risk of tobacco-related cancers and diseases. We did a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, involving 190 controls and 149 cases (incident cancer of the lung, bladder, pharynx, larynx, oral cavity, leukemias, and chronic obstructive pulmonary disease or emphysema deaths). All individuals were never smokers or ex smokers for >10 years. 4-ABP-Hb adducts were analyzed in peripheral blood collected before the onset of the disease (median, 7 years). Overall, 4-ABP-Hb adducts were higher, although not statistically significantly so, in cases (as a whole) than controls. In the control population, high fruit and vegetable consumption significantly lowered the frequency of detectable adducts (Fisher's exact test, P = 0.025). Restricting the analysis to women, 4-ABP-Hb adducts were higher in cases than controls (Mann-Whitney P = 0.036) and the odds ratio (OR) for the presence/absence of adducts was 2.42 [95% confidence interval (95% CI), 1.18-4.98]. Moreover, the association of adducts with the individual cancer types was stronger in women than in the whole study population, although statistically significant only for leukemias (OR, 2.77; 95% CI, 1.06-7.20). The results provide some evidence that women may be more susceptible to environmental tobacco smoke, as suggested by their higher adduct levels. The most important finding of this prospective study is that, at least in women, 4-ABP-Hb adducts may help identify subjects at high risk of cancers related to environmental tobacco smoke exposure.