Personalized Cancer Research Articles

Abstract PR-03: A prospective study of systemic markers of inflammation and risk of esophageal adenocarcinoma in a Barrett's esophagus cohort

Abstract Background: A sustained increase in incidence of and mortality from esophageal adenocarcinoma (EA) has been observed over the past four decades in many developed countries. Persons diagnosed with Barrett's esophagus (BE), a metaplastic condition that confers a 30- to 100-fold increase in EA risk, are typically followed in a surveillance program involving periodic endoscopy with biopsies, with relatively few progressing to EA. No medical, surgical or lifestyle interventions have been proven to safely lower risk of EA. Recently studies have shown that prediagnostic serum inflammation markers may be predictive of cancers of the breast, colon, lung and prostate, but their role in predicting EA is unknown. Methods: We investigated whether elevated serum markers of chronic inflammation, including C-reactive protein (CRP), Interleukin-6 (IL-6) and surface tumor necrosis factor receptors I and II (sTNF-RI & sTNF-RII) could predict progression to EA in a cohort of 411 BE patients followed prospectively. Participants underwent periodic endoscopy with multiple biopsies, personal interview and blood draw. Levels of CRP, IL-6 and sTNF receptors were measured in stored plasma samples using high-sensitivity nephelometry, ELISA and multiplex assay, respectively. For most individuals, two measurements were available - at baseline and the first follow up visit. Their mean was used as the primary predictor. CRP measurements over 10 mg/L were considered to be indicative of acute inflammation and were excluded from the analysis. Adjusted Hazard ratios (HR) were estimated using Cox proportional hazards regression. Results: Median age of the cohort was 61.2 years and 81.3% were males. Median plasma concentrations of all markers were higher among cases (n=56) than among non-cases (CRP 2.65 vs. 1.85 mg/L; IL-6 1.94 vs. 1.87 pg/ml; sTNF-RI 1753 vs. 1378 pg/ml; sTNF-RII 6296 vs. 5337 pg/ml). The main analyses focused on 397 persons with at least 5 months of follow-up (median 78.6 months, 33,635 person-months), in whom 45 developed EA. Elevated CRP was significantly associated with an increased risk of EA after adjustment for age and gender. With CRP modeled as a continuous variable, the HR comparing the 75th%tile vs. 25th%tile was 1.62 (p-trend=0.01; 95% CI 1.12–2.34). Further adjustment for the effects of waist-to-hip ratio, smoking and NSAIDS intake attenuated the association only slightly. Although we found that persons with IL-6 levels above the median had a two-fold increased risk for EA (HR 1.95; 95% CI 1.03–3.72), we did not observe evidence of a trend with increasing concentrations. Increased sTNF receptor levels were not associated with EA risk and we did not observe any trend with increasing sTNF concentrations. Conclusions: Prediagnostic plasma CRP concentrations are predictive of neoplastic progression to cancer in persons with BE. Although there is some suggestion of increased risk with IL-6, there was no significant trend with increasing concentrations. We did not observe any association between levels of sTNF receptors with EA risk. These data support the hypothesis that inflammation may play a significant role in EA development among BE patients, and suggest that serum CRP may be useful in identifying persons at higher risk of progression to cancer. Continued follow-up of this and other larger cohorts is needed to further evaluate CRP and potentially IL-6 as tools for clinical risk stratification among BE patients. Citation Information: Cancer Prev Res 2011;4(10 Suppl):PR-03.

КОЛОРЕКТАЛЬНЫЕ АДЕНОМЫ

Colorectal cancer is a prevalent pathology: its annual incidence reaches a million cases and its annual morbidity rate exceeds 500 thousand people. According to the prognosis, the absolute number of colorectal cancer cases in the world will increase within the next two decades due to the increase of life span and the number of the population in general. Colorectal adenomas are inclined to malignization. The chain adenoma-cancer was proved by numerous research. The risk of the development of rectal and colon cancer in persons with adenomatous polipi is 3-5 times higher than in the general population. In connection with a high risk of the malignant transformation of colorectal adenomas their early diagnosis and timely management are preventive measures to decrease the prevalence of the colorectal cancer.

Abstract A38: Are breast cancer screening patients with family cancer history directed to genetic counseling/testing?

Abstract Background: The death rate from breast cancer for black women in Chicago, Illinois is 62% higher than for white women, and is much higher than the U.S. disparity of 41% and the New York City disparity of 27% (Sinai Urban Health Institute, 2010). The Chicago Breast Cancer Quality Consortium, funded by Susan G. Komen for the Cure Foundation, previously collected data from 43 Chicago hospitals identifying significant quality deficits in breast cancer screening and treatment (Chicago Breast Cancer Quality Consortium, 2010). Women with a BRCA1/2 mutation have a significantly higher risk for breast and ovarian cancer. While most primary care physicians are aware of BRCA testing, only a minority follow guidelines for BRCA evaluation (Bellcross CA, et al 2011). Our aim was to examine the collection of personal and family cancer history during breast cancer imaging and the resulting referrals to genetic counseling/testing that are or are not initiated from the breast imaging care process. Methods: We conducted 113 semi-structured interviews with cross-discipline providers involved in breast cancer screening and care. These interviews were across 26 institutions including 18 community, 4 academic, and 4 public hospitals in the Chicago metro area. Participating institutions provide care to diverse populations. For 22 institution's, African American and Hispanic women comprised more than 50% and for the other 4 institution's more than 30% of the patient population. 10 of the participating community hospitals are classified as low resource. Interviewees included: radiologists, mammography technologists, nurses, surgeons, medical oncologists, internists, administrators, registrars and patient navigators. Interviews were transcribed, thematic analysis was conducted following the framework approach, and statistical analysis was performed using simple frequencies and Fisher's exact test. Results: All (26/26) institutions ask patients at breast cancer screening about their personal and family breast cancer history. One (1/26) institution had a process to refer breast screening patients with a personal or family history to genetic counseling. 10 institutions (38%) had access to genetic counseling within their organizations. Of institutions with internal access to genetic counseling, 80% (8 of 10) referred diagnosed breast cancer patients with familial or personal history to genetic counseling/testing as compared to 31% (5/16) of institutions that do not have internal access to genetic counseling (p=0.0414). Conclusions: While all institutions collected personal and family history of breast cancer, only one institution had a process for and regularly referred appropriate high risk breast screening patients to genetic counseling/testing. Several of the breast imaging centers are now considering methods to implement genetic counseling referrals in their screening protocols. The biggest challenge the institutions noted was not having a clear place to send the patients for genetic counseling. Further research is needed to investigate factors of access to genetic counseling and testing for low resource hospitals serving diverse populations, as well as to develop the needed services and care processes for all institutions participating in our Consortium. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A38.

The positive predictive value of guaiac faecal occult blood test in relation to the number of positive squares in two consecutive rounds of colorectal cancer screening

The aim of this study was to define the positive predictive values of a positive guaiac faecal occult blood test according to the number of positive squares, in two consecutive rounds of colorectal cancer mass screening in a French region. A total of 4172 colonoscopies were analyzed. Sex, age, number of positive squares, and colonoscopic and histopathologic findings were studied. In the results obtained, 76.6% of positive tests were positive with one or two squares. The number of positive squares was not related to sex, age and rank of participation. The positive predictive value for cancers and adenomas increased significantly with age, sex (male) and number of positive squares from 6.6% (one to two squares) to 27.6% (five to six squares) and from 15.2% to 22.2%, respectively. Cancer was diagnosed 211 times (54.1%) and advanced neoplasia was diagnosed 696 times (65.3%) following positive tests with one to two squares. The TNM stage of cancer increased significantly with the number of positive squares: 85.8% of stages 0-1-2 for one to two positive squares and 66.3% for five to six positive squares (P<0.001). Multivariate analysis showed an increased risk of cancer and advanced neoplasia for male patients and aged persons. The number of positive squares significantly increased the risk of cancer (odds ratio=4.6 for five to six positive squares) and the risk of advanced neoplasia (odds ratio=2.9). Age, sex and number of positive squares were independent predictive factors of positive guaiac faecal occult blood test. The proportion of TNM stages 3-4 was significantly higher in those with five to six positive squares. Performing a complete colonoscopy in every individual having a positive test, especially aged men with a high number of positive squares, should be a priority in any screening programme.

Crohn's Disease and Small Bowel Adenocarcinoma: A Population-Based Case–Control Study

Although Crohn's disease (CD) is thought to predispose to adenocarcinomas of the small bowel, the association has not been well studied in an older population. The objective of our study was to evaluate the association of CD with small bowel cancer in a population-based case-control study. All cases of small bowel cancer in persons 67 and older in the Surveillance, Epidemiology and End Results catchment area and in the Medicare claims data base were compared with cancer-free controls residing in the same geographic area. We used multivariable logistic regression models adjusted for demographic and other factors. We identified 923 cases of small bowel cancer and 142,273 controls. Although we found a strong association between CD and small bowel cancer (OR = 12.07; 95% CI: 6.07-20.80; P < 0.001), the prevalence of CD in patients with small bowel cancer was low (1.6%). Although CD is a significant risk factor for small bowel cancers among individuals older than 67, the absolute risk is small. Older individuals with CD can be reassured that although there is an association between CD and small bowel cancer, the absolute risk remains small.

Proportions of Kaposi Sarcoma, Selected Non-Hodgkin Lymphomas, and Cervical Cancer in the United States Occurring in Persons With AIDS, 1980-2007

Given the higher risk of AIDS-defining malignancies that include Kaposi sarcoma (KS), certain non-Hodgkin lymphomas (NHLs), and cervical cancer in persons with human immunodeficiency virus (HIV) infection, the HIV epidemic has likely contributed to the overall numbers of these cancers in the United States. To quantify the proportions of KS, AIDS-defining NHLs, and cervical cancer in the United States that occurred among persons with AIDS from 1980 to 2007. The HIV/AIDS Cancer Match Study (1980-2007) linked data from 16 US HIV/AIDS and cancer registries to identify cases with and without AIDS for KS, AIDS-defining NHLs (ie, diffuse large B-cell lymphoma [DLBCL], Burkitt lymphoma [BL], and central nervous system [CNS] lymphoma), and cervical cancer. Using linked data, we derived cancer rates for persons with and without AIDS. To estimate national counts, the rates were applied to national AIDS surveillance and US Census data. Proportion of AIDS-defining malignancies in the United States occurring in persons with AIDS. In the United States, an estimated 81.6% (95% confidence interval [CI], 81.2%-81.9%) of 83,252 KS cases, 6.0% (95% CI, 5.8%-6.1%) of 351,618 DLBCL cases, 19.9% (95% CI, 18.1%-21.7%) of 17,307 BL cases, 27.1% (95% CI, 26.1%-28.1%) of 27,265 CNS lymphoma cases, and 0.42% (95% CI, 0.37%-0.47%) of 375,452 cervical cancer cases occurred among persons with AIDS during 1980-2007. The proportion of KS and AIDS-defining NHLs in persons with AIDS peaked in the early 1990s (1990-1995: KS, 90.5% [95% CI, 90.2%-90.8%]; DLBCL, 10.2% [95% CI, 9.9%-10.5%]; BL, 27.8% [95% CI, 25.0%-30.5%]; and CNS lymphoma, 48.3% [95% CI, 46.7%-49.8%]; all P < .001 [compared with 1980-1989]) and then declined (2001-2007: KS, 70.5% [95% CI, 68.1%-73.0%]; DLBCL, 4.7% [95% CI, 4.3%-5.2%]; BL, 21.5% [95% CI, 17.7%-25.4%]; and CNS lymphoma, 12.9% [95% CI, 10.5%-15.3%]; all P < .001 [compared with 1990-1995]). The proportion of cervical cancers in persons with AIDS increased over time (1980-1989: 0.11% [95% CI, 0.09%-0.13%]; 2001-2007: 0.71% [95% CI, 0.51%-0.91%]; P < .001). In the United States, the estimated proportions of AIDS-defining malignancies that occurred among persons with AIDS were substantial, particularly for KS and some NHLs. Except for cervical cancer, the proportions of AIDS-defining malignancies occurring among persons with AIDS peaked in the mid-1990s and then declined.

Is Inflammatory Bowel Disease an Important Risk Factor Among Older Persons with Colorectal Cancer in the United States? A Population-Based Case–Control Study

While ulcerative colitis (UC) and Crohn's disease (CD) are thought to predispose to colorectal cancer (CRC), the association has not been well studied in an older population. The objective of our study was to evaluate the association of ulcerative colitis and Crohn's disease and colorectal cancer in a population-based, case-control study. We also wished to estimate the incidence rates of colorectal cancer among older individuals with UC/CD. All cases of colorectal cancer in persons 67 and older in the SEER catchment area and in the Medicare claims database were compared with cancer-free controls residing in the same geographic area. We used multivariable logistic regression models adjusted for demographic and other factors. We identified 47,543 cases of CRC and 142,273 controls. We found a modest association between UC and CRC (OR 1.93; 95% CI 1.54-2.49; P-value<0.001) and a significant, albeit modest, association between CD and CRC (OR 1.45; 95% CI 1.08-1.91; P-value 0.01). We found the incidence of CRC to be 8.2 per 10,000 person-years (95% CI 6.5-10.1/10,000 person-years) among those with UC/CD, and 6.1 per 10,000 person-years (95% CI 4.6-7.8/10,000 person-years) among those without UC/CD, resulting in an incidence rate ratio of 1.34. Among older persons ulcerative colitis and Crohn's disease are modest risk factors for CRC, and the incidence rate ratio for CRC is modest, suggesting that risk of CRC in patients with IBD may be lower than previously thought.

Protection From Colorectal Cancer After Colonoscopy

Colonoscopy with detection and removal of adenomas is considered a powerful tool to reduce colorectal cancer (CRC) incidence. However, the degree of protection achievable in a population setting with high-quality colonoscopy resources remains to be quantified. To assess the association between previous colonoscopy and risk for CRC. Population-based case-control study. Rhine-Neckar region of Germany. A total of 1688 case patients with colorectal cancer and 1932 control participants aged 50 years or older. A detailed lifetime history of CRC risk factors and preventive factors, including history and results of previous colonoscopies, and of medical data obtained by self-reports and medical records. Odds ratios of CRC associated with colonoscopy in the preceding 10 years were estimated, after adjustment for sex, age, education level, participation in a general health screening examination, family history of CRC, smoking status, body mass index, and use of nonsteroidal anti-inflammatory drugs or hormone replacement therapy. Overall, colonoscopy in the preceding 10 years was associated with 77% lower risk for CRC. Adjusted odds ratios for any CRC, right-sided CRC, and left-sided CRC were 0.23 (95% CI, 0.19 to 0.27), 0.44 (CI, 0.35 to 0.55), and 0.16 (CI, 0.12 to 0.20), respectively. Strong risk reduction was observed for all cancer stages and all ages, except for right-sided cancer in persons aged 50 to 59 years. Risk reduction increased over the years in both the right and the left colon. The study was observational, with potential for residual confounding and selection bias. Colonoscopy with polypectomy can be associated with strongly reduced risk for CRC in the population setting. Aside from strong risk reduction with respect to left-sided CRC, risk reduction of more than 50% was also seen for right-sided colon cancer. German Research Council and German Federal Ministry of Education and Research.

The role of residence near hazardous waste sites containing benzene in the development of hematologic cancers in upstate New York

Epidemiologic studies suggest an association between environmental exposure to benzene and hematologic cancers, but the relationship is not firmly established. The aim of this study was to assess the potential association between residence near hazardous waste sites containing benzene and hospitalization discharge rates for persons having hematologic cancers. We determined the number of hospital discharges of people with hematologic cancers in New York State except for New York City for the years 1993 to 2008.Descriptive statistics and negative binomial regression models were used to compare the rates of hospitalization of residents in zip codes containing hazardous waste sites containing benzene to the rates of discharges from residents in zip codes without waste sites. When adjusting for potential confounders we found a 15% increase in the rate of hospitalization for chronic lymphatic leukemia (CLL) [rate ratio (RR): 1.15; 95% confidence interval (CI): 1.00-1.33], a 22% increase in the rate of discharges for total leukemia (RR: 1.22; 95% CI: 1.04-1.43) and a 17% increase in the rate of discharges for total lymphoma (RR: 1.17; 95% CI: 1.02-1.35) in the benzene exposed sites. We found greater effects of exposure in African Americans compared to Caucasians, females compared to males and people with higher socioeconomic status (SES) compared to those with lower SES for several of the diseases studied. After controlling for major confounders we found statistically significant increases in discharge rates for several hematologic cancers in persons residing in zip codes containing benzene waste sites. These results provide additional support for a relationship between environmental exposure to benzene and risk of hematologic cancers.

Cancer genomes and clinical care

Stratifying individual patients for specific therapies based on the clinical stage and morphological features (phenotype) of their disease is the basis of modern clinical oncology. Appropriate therapeutic regimens are selected in light of the characteristics of an individual’s cancer based on imaging and histopathology, which are indirect ‘surrogate’ measures of disease biology. Advances in molecular pathology and our understanding of cancer biology have led to refinement of existing clinico-pathological phenotypes, and in some cases such as leukaemia and breast cancer, a new molecular taxonomy has emerged which is integral to the modern management of these diseases. Increasingly, the development of a novel targeted therapy involves defining drug-diagnostic combinations where the presence of a molecular marker identifies patients who are most likely to respond to treatment. This model of developing treatment and diagnostic/companion biomarker combinations in order to target patient populations with a greater chance of benefiting from treatment is the emerging paradigm for new drug and diagnostic development. This strategy is facilitating significant advances in some cancer types, with one of the more recent examples being the successful use of the BRAF inhibitor PLX4032, which targets a specific mutation (V600E) in melanoma. The number of target-drug combinations with efficacy is growing, and some are suggesting that the era of personal genomic cancer therapy is already here. This emerging paradigm is changing the focus from therapeutic strategy development to diagnostics and will create significant challenges in the development and delivery of personalised medicine strategies. The Australian Pancreatic Cancer Genome Initiative, a part of the International Cancer Genome Consortium, aims to define, interpret and apply cancer genomic data. Direct potential clinical applications include the delineation of phenotypes based on patterns of genomic aberrations co-segregating with clinico-pathological endpoints and identifying druggable mutations. In addition, other approaches such as the detection of tumour specific genomic abnormalities in blood would have applications in early detection of recurrence and surrogate markers of therapeutic responsiveness. These advances are rapidly altering diagnostic and therapeutic strategies for cancer, and potentially other diseases, paving the way to genomic health. These advances in genetic pathology have the potential to refine, and possibly replace current morphology based diagnostic approaches.

The analysis of case-control studies of the efficacy of screening for recurrence of cancer

Occasionally, the efficacy of screening for cancer recurrence has been evaluated by means of case-control studies. However, these studies generally have not been designed and analyzed in a manner that will yield an unbiased result. The commentary shows that by adhering to the principles developed for the analysis of studies of the efficacy of screening for the presence of a given cancer in persons with no history of this disease, a case-control study of screening for recurrence will improve its chances of obtaining valid findings.

Association between N142D genetic polymorphism of GSTO2 and susceptibility to colorectal cancer

Expression pattern analysis has been revealed that glutathione S-transferase omega 2 (GSTO2, a member of class omega) is ubiquitously expressed. Over expression of GSTO2 induced apoptosis. The gene encoding GSTO2 was localized to human chromosome 10q24.3, a region that may harbor gene(s) involved in the developing of colorectal cancer. To investigate the association between GSTO2 N142D genetic polymorphism and susceptibility to colorectal cancer the present study was done. We studied 63 (26 females, 37 males) colorectal cancer patients and 126 (52 females, 74 males) healthy individuals. The control subjects were frequency matched for age and gender with the colorectal cancer group. The genotypes were performed using RFLP-PCR method. The ND and DD genotypes were not associated with risk of colorectal cancer, in comparison with the NN genotype. Family history for cancer in the first degree of relatives significantly differed between cases and controls (P = 0.012). The profiles of GSTO2 genotypes and family history in control and cancerous groups were compared to each other. Subjects with NN genotype and positive family history significantly were at high risk to develop colorectal cancer in comparison with subjects with DD or ND genotypes and negative family history (P = 0.003). Present findings indicating that GSTO2 NN genotype increase the risk of colorectal cancer in persons with positive family history for cancer in the first degree relatives.

Biomarker Research in Breast Cancer

Breast cancer is a heterogeneous disease with vast differences between patients regarding treatment response and prognosis. Therefore, strategies for individualizing care are needed. The rapid developments in biomarker research in breast cancer are making personalized breast cancer therapy a reality. A biomarker is defined as an objectively measured characteristic that can be evaluated as an indicator of normal biologic processes, pathogenic processes, or therapeutic responses. Biomarkers can have prognostic or predictive value. A small group of individual biomarkers has been used in the management of breast cancer, including estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Advances in molecular biology and an increased understanding of tumor cell biology have led to the discovery of a vast array of promising new biomarkers, including cancer stem cells, circulating tumor cells, gene-expression profiles, individual response markers, disease subtypes, predictors of metastasis, and mutation markers. To be adopted into routine practice, these candidate biomarkers will require extensive clinical validation. The improved application of traditional biomarkers and the discovery of additional markers will undoubtedly change the face of breast cancer care.

Risk of skin cancer after neonatal phototherapy: retrospective cohort study

ObjectiveTo assess the risk of skin cancer in persons treated with neonatal phototherapy (NNPT) for jaundice.DesignRetrospective cohort study.SettingGrampian Region, Scotland, UK.Data sourceAberdeen Maternity and Neonatal Databank. NNPT exposure was abstracted...

Gene test hope for personalised breast cancer treatment

Gene test hope for personalised breast cancer treatment

Abstract CN04-04: Cancer predisposition: I say genetics, you say genomics, but are we there yet?

Abstract In the United States, major contributors to premature mortality are behavior (40%) and genetics (35%). Amongst all diseases, scientific knowledge regarding genetic predisposition to cancer is one of the most advanced. Based on multidisciplinary research spanning the last 2 deacdes, the practice of clinical cancer genetics has empowered patients, their family members and healthcare providers with genetics-informed cancer risk assessment and management. On average, 10% of all cancers are caused by a strong (high penetrance) genetic predisposition, with a range between 5% and 30%. Yet, are those at genetic risk for cancer reaching proper care for prevention? An interactive-electronic family cancer history survey performed in a cancer hospital serving the population of central Ohio revealed that only 7% of all those assessed by cancer genetics professionals to be at high risk for cancer predisposition were recognized either by the patients' healthcare providers or the patients themselves, and referred to cancer genetics professionals. A recent national survey of &amp;gt;35,000 women without personal breast or ovarian cancer histories revealed that ∼1% (∼350) were at high risk for breast and/or ovarian cancer based on family history alone (i.e., at risk for carrying BRCA1/2 mutation). Yet, of these ∼350, only 10% (∼35) discussed this genetic risk with any healthcare provider, and only ∼1.5% (∼4) had BRCA1/2 gene testing. BRCA1/2 are “the most popular”” breast cancer predisposition genes and yet this population is under-serviced. There are at least 6 other high penetrance breast cancer-predisposition genes, including PTEN. Because of the lack of a systematic manner of identifying and managing all individuals at genetic risk for cancer, the great majority of individuals at high risk for cancer predisposition are never identified (in this BRCA1/2 national survey, 90%) nor reach appropriate medical care (99%). Therefore, we believe that individuals and their families at genetic risk for cancer are an under-served population. Paradoxically or perhaps due to the lack of knowledge of the availability and the power of validated genetics services, direct-to-consumer (DTC) personal genome scanning or screening has begun to gain popularity or at least peak public interest. In contrast to validated genetic testing, that is always focused on one or very few genes guided by medical and family histories, personal genomic scanning is currently based on multiple statistical comparisons called genome-wide association. Validated genetic testing is offered by healthcare providers to individuals at high risk of Mendelian genetic disease. This model of validated Mendelian genetic testing focuses only on one or a few genes that are known to be strongly associated with disease. If a gene mutation is identified, the individual is at high risk (sometime ∼100% likelihood) of developing the associated disease, and this type of genetic knowledge is clinically utile and actionable for prevention or very early detection. A few examples include Lynch syndrome, hereditary breast-ovarian cancer syndrome and Cowden syndrome. Personal genomic screening, or personal genome testing or profiling, uses data derived from genome-wide association studies to predict an individual's probability of developing many different disorders and traits in a lifetime. The majority of such genome-wide association studies are case-control studies which study hundreds to thousands of individuals to search for genetic markers shown to be statistically more common in individuals with disease compared with controls. These genetic markers are most commonly Single Nucleotide Polymorphisms (SNPs). They are common in the general population and may or may not have a known functional consequence. These types of data usually provide an odds ratio or relative risk of the likelihood that an individual with a particular genotype will have disease. As a result, most such DTC scanning currently has no to little analytic validity (because SNP choice and algorithms may differ), no clinical validity, no clinical utility and no actionability. Thus, interdisciplinary research directed at clinical outcomes or subsets of individuals or clinical situations where they can be used in a valid and actionable way should be performed. Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN04-04.

Helicobacter Pylori and Gastroduodenal Ulcer Disease

Helicobacter pylori-associated diseases and gastroduodenal ulcer disease are common conditions of major clinical and economic importance. There is thus a need for a guideline that incorporates the scientific knowledge gained in recent years and that takes specific aspects of the situation in Germany into account with regard to epidemiology, resistance status, diagnostic evaluation, and treatment. This level-S3 consensus guideline was developed in accordance with the recommendations of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). It was commissioned by the German Association for Digestive and Metabolic Diseases (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten, DGVS) and prepared in cooperation with other scientific societies. After search terms were compiled, a systematic, IT-supported literature search was performed in the PubMed and Cochrane databases. The search was restricted to articles that appeared in German or English from 2000 onward. H. pylori infection can be accurately diagnosed either non-invasively (with a (13)C-urea breath test or a stool antigen test) or invasively (with a rapid urease test, by histology, or by culture). Gastric and duodenal ulcer and gastric MALT lymphoma are absolute indications for eradication therapy; relative indications include functional dyspepsia, the prevention of gastric cancer in persons at risk, the initiation of long-term treatment with non-steroidal anti-inflammatory drugs (NSAID), and the prior occurrence of gastroduodenal complications with the use of either NSAID or acetylsalicylic acid (ASA). First-line therapy consists of a proton-pump inhibitor (PPI) and clarithromycin combined with either metronidazole or amoxicillin, given for at least one week. This guideline enables the structured, evidence-based diagnosis and treatment of H. pylori infection and associated conditions, as well as of gastroduodenal ulcer disease.

Identifikation von Personen mit familiärem oder hereditärem Darmkrebsrisiko mittels eines Fragebogens zur Familienanamnese

The overall aim of the present work was to estimate the potential of early detection of colorectal cancer in persons with familial or hereditary risk. In this paper we present projections on how many persons in the age groups 30 - 49 and 30 - 54 years, respectively, would be classified as being at familial or hereditary risk when a questionnaire distributed by the "Netzwerk gegen Darmkrebs e. V." (network against colon cancer) is used for identification. Based on the results of a systematic literature search on the validity of questionnaires, the estimated prevalence of familial and hereditary disposition for colorectal cancer as well as actual German tumour incidence data projections were calculated. Given a 10 % prevalence of persons with a familial risk in the German general population and a maximum knowledge of all tumour cases in kindred, a total of 5.7 % of all Germans in the age group 30 - 49 years would be classified as familial risk persons (7.2 % in the age group 30 - 54 years). Taking familial and hereditary risks into account 6.7 % (8.2 %) will have a positive questionnaire result. If the questionnaire is used on a population-based level and the participation rate is 35 %, approximately 542 000 persons in the age group 30 - 49 years (816 000 in the age group 30 - 54 years) will be classified as having a familial or hereditary risk for colorectal cancer.

Genetische Krebsdiagnostik

Genetic diagnostics can make the prognosis of a malignant disease more precise, and its importance will increase in the future. The relatives of a patient with an inherited cancer syndrome can be examined for tumor predisposition through predictive genetic diagnostics. This possibility is important for risk-adapted early cancer recognition. Inherited breast/ovary cancer and inherited forms of bowel cancer are examples of successful application of this concept. Knowledge about a personal high cancer risk is a burden for the individual, so individualized genetic and clinical counseling is a prerequisite for good compliance of someone at high risk for cancer. Studies have shown that even a positive predictive test result is less burdensome for people than continuing uncertainty about their own risk situation. Patients and their families with inherited cancer predisposition should be supported in specialized centers. Modern genetics opens preventive and therapeutic options and can be reassuring, but it is neither a blessing nor a curse.

Nonmelanoma Skin Cancer in Persons of Color

Skin cancer is the most common form of cancer in the United States. Although skin cancer is less common in persons of color than in Caucasians, the rates of morbidity and mortality associated with skin cancer often are significantly greater in darker-skinned ethnic groups. This article reviews special considerations in the approach and management of nonmelanoma skin cancer in patients of color.