Cancer Etiology and Epidemiology

Cancer Etiology and Epidemiology
   

• CB Begg. LD Cramer, WJ Hoskins [ Mem Sloan-Kettering Cancer Ctr, New York]
  Impact of Hospital volume on Operative Mortality for Sloan-Kettering Cancer Surgery
  JAMA 280: 1747- 1751, 1998
    
  In this article the authors have tried to correlate the mortality within 30 days of major surgery such as pancreatectomy, esophagectomy, pneumonectomy with resection or pelvic exenteration to the volume of work after adjusting for case mix and investigated in a retrospective cohort study. High volume significantly decreased the mortality for all procedures except pneumonectomy. The effect of volume was particularly evident on esophagectomy and for pancreatectomy. The editor comments that the data from this study should be evaluated carefully as all the payers including Medicare, begin to scrutinize cancer care patterns and results.
     

• JF Stratton, P Pharoah, SK Smith, et al [ Addenbrooke’s Hosp, Cambridge England; Univ of Cambridge, England, Rosie Maternity Hosp, Cambridge, England]
  A Systemiatic Review and Meta-analysis of Family History and Risk of Ovarian Cancer
  Br J Obstet Gynaecol 105 : 493-499; 1998
     
  This study is a meta analysis of fifteen studies between 1979 and 1996 to calculate the risk of relation of patients with ovarian cancer of either having or dying from ovarian cancer. First degree relations have a relative risk of 3.1. Some evidence suggested that this relative risk decreases with age. Mothers of patients had a relative risk of 1.1 compared to 3.8 for sisters & 6.0 for daughters. This study confirms the conclusion that women with family history of ovarian cancer has a markedly higher risk of ovarian cancer. However, this risk is small except for those with more than one affected relative, in that situation the risk ranged from 3.0% to 23.5%. The editor comments that this risk is consistent with an underlying ovarian cancer – susceptible genes BRCA1 and BRCA2 which are tumor suppressor genes associated with the breast /ovarian cancer tumor syndrome and mismatch repair genes associated with hereditary non-polyposis colorectal cancer families. The data from this meta-analysis would be useful for appropriate counseling of patients with a family history of ovarian cancer.
     

• Narod SA, for the Hereditary Ovarian Cancer Clinical Study Group [Univ of Toronto; et al]
  Oral Contraceptives and the Risk of Hereditary Ovarian Cancer
  N Engl J Med 339: 424-428, 1998
     
  In this study 207 women with hereditary ovarian cancer and with a pathogenic mutation in either BRCA1 or BRCA2 gene were studied along with 161 of their sisters. The study findings revealed women using oral contraceptive [OC] for 6 or more years had a 60% reduction in the risk of ovarian cancer. The use of OC protected against ovarian cancer among the carriers of both to BRCA1 or BRCA2 mutation.
      

• Lombard I, Vincent-Salomon, Validire P, et al [ Institut Curie,Paris; Institut Pasteur, Paris]
  Human Palillomavirus Genotype as a Major Determinant of the Course of Cervical Cancer
  J Clin Oncol 16: 2613-2619, 1998
     
  Human Papillomavirus [HPV] a venereally transmissible oncogenic agent, is a well known to be associated with of uterine cervix. In this study HPV DNA was extracted from frozen tumor specimens analyzed by Southern blot hybridization and polymerase chain reaction. 
    
  The genotype HPV 16 & HPV18 positive tumors had a disease free survival at 5 year of 58% and 38% respectively. A multivariate analysis recorded HPV-18 related tumors with a relative risk of death that was 2.4 times higher than were HPV-16 related tumors and a 4.4 times higher than tumors related to other viral types. The editor comments that typing of HPV is clearly a prognostic indicator for individual patients with cervical cancer and further management of these patients would be through biological and immunological therapies directed against HPV associated carcinoma.
     

• Penninx BWJH, Guralnik JM, Pahor M, et al [ Natl Inst on Aging, Bethesda, Md; Univ of Tennessee, Memphis; Istituto Nazionale Ricerca e Cura Per Gli Anziani, Florence, Italy; et al]
  Chronically Depressed Mood and Cancer Risk in Older Persons
  J Natl Cancer Inst 90: 1888-1893, 1998
       
  The associations of chronic depression with cancer in elderly patients was investigated. All participants in this study were 71 years or older.
     
  Depression of at least 6 years duration appears to be associated with an increased risk of cancer in elderly even when corrected for factors such as alcohol smoking, age, sex and race. The editor comments that depressed patients practice poorer health promoting behavior than non depressed and could be attributed to increased cancer risk.
      

• Granovsky MO, Mueller BU, Nicholson HS, et al [ Natl Cancer Inst, Bethesda, Md; Children’s Hosp, Boston; Children’s Natl Med Ctr, Washington, DC]
  Cancer in Human Immunodeficiency Virus-Infected Children: A Case Series From the Children’s Cancer Group and the National Cancer Institute
  J Clin Oncol 16: 1729-1735, 1998
     
  The epidemiology of HIV-related cancer in adults has been well described but that in children is not well documented and hence this study reports the spectrum of malignancies in HIV infected children and their clinical outcome.
     
  Most [58%] of the children had acquired HIV vertically 34% through blood or blood products transfusion. Non-Hodgkin’s lymphoma – 65% was the commonest followed by leiomyosarcomas – 17% and the others were acute leukemia. Kaposi’s sarcoma, Hodgkin’s disease vaginal carcinoma in situ tracheal neuroendocrine tumor. The median survival for NHL was 6 months and leiomyosarcoma – 12 months after diagnosis. The editor comments that with recent improvements in antiretroviral therapy and supportive care. More children are surviving the early complications of HIV and will subsequently develop malignancies.
      

• Bennet CL, Ferreira MR, Davis TC, et al [ Chicago Veteran Affairs Administration Healthcare System-Lakeside Division; Lurie Cancer Ctr; Northwestern Univ, Chicago; et al
  Relation between Literacy, Race, and Stage of Presentation Among Low-Income Patients with Prostate Cancer
  J Clin Oncol 16: 3101-2104, 1998
     
  Advanced prostate cancer in a low income men is related to poor literacy skill has been brought out in this study. The black men were almost twice as likely as white men to have stage D prostate cancer at initial examination. The editor comments that the effectiveness of screening to detect cancer at the earlier stage depends on aggressiveness of the tumor, the cost effectiveness of screening and most importantly, the willingness of the patient to undergo screening. The importance of the literacy for the informed consent has direct implications in clinical trials.
       

• deVere White RW, Deitch AD, Jackson AG, et al [ Univ of California, Davis; Northern California Cancer Ctr, union City; Howard Univ, Washington, DC]
  Racial Differences in Clinically Localized Prostate Cancers of Black and White Men
  J Urol 159: 1979-1983, 1998
    
  The investigative skill i.e prostate-specific antigen and proper records in cancer registries, are responsible for the increase in prostate cancer despite these a true rise in incidence of prostate cancer is noted. The highest incidence in the world is found among black men in Unites States; They have at younger age, large volume, higher stage and grade compared with white men. This study has correlated with biological markers i.e. deoxyribonucleic acid ploidy by DNA flow cytometry using propidium / expression of proliferation, as well as P53 & bcl-2 . A monoclonal antibody cocktail for p53 and clone 124 antibody for bcl-2 were used for immunostaining after microwave antigen retrieval on the prostate biopsy specimens. The higher S phase fraction reflecting high proliferation and bcl-2 immnuno positively i.e. block to programmed cell death- characterize the aggressive prostate cancer of black men.
       

• Manel Esteller, Jesus Garcia Foncillas et al
  Inactivation of the DNA repair gene MGMT and the clinical response of gliomas to alkylating agents.
  New Eng J Med. Vol.343, Nov.9, 2000,pg.1350.
    
  Summary: The DNA repair enzyme O6-methyl-guanine-DNA methyltransferase (MGMT) inhibits the killing of tumour cells by alkylating agents. MGMT activity is controlled by a promoter and methylation of the promoter silences the gene in cancer and the cells no longer produce MGMT. Authors examined gliomas to determine whether methylation of the MGMT promoter is related to the responsiveness of the tumour to alkylating agents.
  
  MGMT promoter in tumour DNA was analysed by a specific PCR assay. Gliomas were obtained from patients treated with carmustine. Molecular data were correlated with the clinical outcome. MGMT promoter was methylated in 40% of gliomas and this was associated with regression of the tumour and prolonged overall and disease free survival. It was an independent and stronger prognostic factor than age, stage, tumour grade or performance status.
  
  The conclusion was that methylation of the MGMT promoter in gliomas is a useful predictor of responsiveness of the tumours to alkylating agents.
  
  Editorial : John N Weinsten, pg.1408
  Pharmacogenomics – Teaching old drugs new tricks.
  Summary: Traditionally, cancer treatments have been selected on the basis of tumour type, pathological features, clinical stage, the patient’s age and performance status and other nonmolecular considerations. The field of pharmacogenomics, through the study of large number of genes that influence drug activity, toxicity and metabolism, provides the opportunity to tailor drug treatments and to eliminate many of the uncertainties of current therapy for cancer.
  
  Strong support for this concept is provided by the study of genetic polymorphisms that influence drug metabolism. CYP2D6 affects metabolism of several drugs (beta-blockers, antidepressants, antipsychotics and opioids). Dihydropyrimidine dehydrogenase influences metabolism and therefore neurotoxicity of fluorouracil.
  
  Esteller and colleagues provide clinical evidence to explain the resistance of some gliomas to nitrosourea alkylating agents. Carmustine and other nitrosoureas kill by alkylating O6 position of guanine and thereby cross-linking adjacent strands of DNA. Formation of these cross-links can be prevented by MGMT, which rapidly reverses alkylation. About 30% of gliomas lack MGMT. A lack of MGMT appears to correlate with sensitivity to carmustine. Methylation of MGMT promoter could be used to predict responses to treatment with carmustine.
  
  Pharmacogenomics studies will produce benefits both for clinical research and standard practice. Potential advantages include discovery of better drugs, elimination of poor candidates early in the development process, and dramatic decrease in size and expense of clinical trials.
    

• Scott Gottlieb, New York
  Cancer drug may cause heart failure
  BMJ, Vol.321, July 29, 2000, pg.259.
    
  Trastuzumab (Herceptin) is a monoclonal antibody that binds to a protein found on the surface of some cells. The protein, HER2, helps to regulate cell growth. By binding to tumour cells, trastuzumab inhibits growth of cancerous cells. It is currently approved for use in metastatic breast cancer.
  
  Editorial in ‘Circulation’ has reported that heart failure occurs in 7% of women taking trastuzumab alone and this rate increases to 28% in women taking the drug with other chemotherapy drugs.
  
  A team of researchers is calling for long-term studies investigating the risk of heart failure among women taking trastuzumab.
   

• Freifeld A, D Marchigiani, T Walshi, et al (NIH, Bethesda, Md; Univ of South Florida, Tampa; Harvard Med School, Boston)
  A Double-blind Comparison of Empirical Oral and Intravenous Antibiotic Therapy for Low-risk Febrile Patients with Neutropenia During Cancer Chemotherapy.
  N Engl J Med 341: 305-311, 1999.
     
  Oral antibiotic [Amoxicillin + Clavulanate + Ciprofloxacin] in febrile neutropenia for patients with low risk of complications is an acceptable propositions as this randomized double blind placebo control study has proved.
     

• Kern WV, for the International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatmetn of Cancer (Medizinische Universitatsklinik und Poliklinik, Ulm, Germany)
  Oral Versus Intravenous Empirical Antibmicrobial Therapy for Fever In Patients with Granulocytopenia who are Receiving Cancer Chemotherapy.
  N Engl J Med 341: 312-318, 1999.
    
  In low risk granulocytopenia patients following cancer chemotherapy oral antibiotics [amoxicillin + clavulanate + ciprofloxacin] is as effective as intravenous antibiotics [ceftriaxone + amikacin]. Success rate outcomes and frequency of adverse effects were comparable between both the groups.
      

• Chorost MI, Weber TK, et al (Roswell Park Cancer Inst, Buffalo, NY)
  Sexual Dysfunction, Informed Consent and Multimodality Therapy for Rectal Cancer
  Am J Surg 179: 271-274, 2000
    
  This retrospective study was reviewed for 53 consecutive patients who had undergone surgery and or radiation for rectal cancer. Sexual dysfunction occurred in 5/15 men who had undergone abdominoperineal resection (APR) and 6/8 men with APR and radiation (75%). No presurgical discussion as regards these side effects were discussed.
    
  The editor comments the importance of this study is in understanding our own inadequacies.
      

• SÆrensen HT, Mellemkjaer L, et al (Aarhus Univ, Denmark; Inst of Cancer Epidemiology, Copenhagen; Dartmouth Med School, Hanover, NH)
  Prognosis of Cancers Associated With Venous Thromboembolism
  N Engl J Med 343: 1846-1850, 2000
    
  This study from Danish National Registry and Danish Cancer Registry tried to analyze association between a history of venous thromboembolism and extent of disease at the time of cancer diagnosis.
    
  Patients with diagnosis of cancer within 1 year after venous thromboembolism had a slightly increased risk of distant metastasis and lower rates of survival at one year.
    
  The editor comments that angiogenic research suggests the stromal and endothelial cells interactions are critical for cancer dissemination and tumor growth.
    

• Johannsson O, loman n, et al (Univ Hosp, lund, sweden)
  incidence of malignant tumors in relatives of BRCA1 and BRCA2 germline mutation carriers
  eur j cancer 35: 1248-1257, 1999
    
  This incidence of malignant tumor among 1873 members of 29 BRCA1, and 20 BRCA2 families were identified as 150 malignant tumors in BRCA1 families and 87 BRCA2 families.
   
  Women in BRCA1 families had significant increases in breast, ovary and stomach cancers whereas in BRCA2 families only had breast cancer. Other malignancIES in male were invasive squamous cell cancer of skin.
   
  The editor comments that this article provides us the information that other cancer types beyond breast and ovarian cancer are not significantly increased and cannot warrant extended screening.
     

• Swerdlow AJ, Higgins CD, et al (London school of hygiene & tropical medicine; imperial college school of medicine, london; harefield hosp, middlesex, england)
  risk of lymphoid neoplasia after cardiothoracic transplantation: a cohort study of the relation to epstein-Barr virus
  transplantation 69: 897-904, 2000
     
  Cardiothoracic tranplantation dramatically increases the risk of lymphoid neoplasia and many of these tumors express Epstein-Barr Virus (EBV) DNA.
   
  This retrospective evaluation of the risk of lymphoma is 1500 patients who underwent heart, lung tranplantation. The risk of lymphoproliferative disorder (LPD) peaked at 6 months and then declined.
    
  The LPD risk was 10 times higher for those who had EBV seronegative status prior to transplantation and then had a primary EBV infection with seroconversion. This study highlights the requirements for prophylactic strategies for curtailing EBV infection.