Occupational and Environmental Exposures Associated with Testicular Germ Cell Tumours: Systematic Review of Prenatal and Life-Long Exposures

Background Testicular germ cell tumours (TGCT) are the most common cancers in men aged between 15 and 44 years and the incidence has increased steeply over the past 30 years. The rapid increase in the incidence, the spatial variation and the evolution of incidence in migrants suggest that environmental risk factors play a role in TGCT aetiology. The purpose of our review is to summarise the current state of knowledge on occupational and environmental factors thought to be associated with TGCT. Methods A systematic literature search of PubMed. All selected articles were quality appraised by two independent researchers using the ‘Newcastle-Ottawa Quality Assessment Scale’. Results After exclusion of duplicate reports, 72 relevant articles were selected; 65 assessed exposure in adulthood, 7 assessed parental exposures and 2 assessed both. Associations with occupation was reported for agricultural workers, construction workers, firemen, policemen, military personnel, as well as workers in paper, plastic or metal industries. Electromagnetic fields, PCBs and pesticides were also suggested. However, results were inconsistent and studies showing positive associations tended to had lower quality ranking using the assessment scale (p=0.02). Discussion Current evidence does not allow concluding on existence of any clear association between TGCT and adulthood occupational or environmental exposure. The limitations of the studies may partly explain the inconsistencies observed. The lack of association with adulthood exposure is in line with current hypotheses supporting the prenatal origin of TGCT. Future research should focus on prenatal or early life exposure, as well as combined effect of prenatal and later life exposure. National and international collaborative studies should allow for more adequately powered epidemiological studies. More sophisticated methods for assessing exposure as well as evaluating gene–environment interactions will be necessary to establish clear conclusion.

[1]  Lisa Hartling,et al.  Testing the Newcastle Ottawa Scale showed low reliability between individual reviewers. , 2013, Journal of clinical epidemiology.

[2]  I. Bryngelsson,et al.  Cancer incidence among Swedish pulp and paper mill workers: a cohort study of sulphate and sulphite mills , 2013, International Archives of Occupational and Environmental Health.

[3]  O. Löfman,et al.  Health effects and exposure to polychlorinated biphenyls (PCBs) and metals in a contaminated community. , 2012, Environment international.

[4]  K. McGlynn,et al.  Adolescent and adult risk factors for testicular cancer , 2012, Nature Reviews Urology.

[5]  S. Brunak,et al.  A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation , 2011, Journal of Medical Genetics.

[6]  W. Ahrens,et al.  Exposure to metal-working fluids in the automobile industry and the risk of male germ cell tumours , 2011, Occupational and Environmental Medicine.

[7]  I. Figa-talamanca,et al.  Pesticide exposure and serum organochlorine residuals among testicular cancer patients and healthy controls , 2011, Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes.

[8]  A. Harding,et al.  Mortality and cancer incidence among British agricultural pesticide users. , 2011, Occupational medicine.

[9]  J. Atkinson,et al.  Ethnic and socioeconomic trends in testicular cancer incidence in New Zealand , 2011, International journal of cancer.

[10]  B. Cohn,et al.  Prenatal DDT Exposure and Testicular Cancer: A Nested Case-Control Study , 2010, Archives of environmental & occupational health.

[11]  A. Stang Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses , 2010, European Journal of Epidemiology.

[12]  N. Skakkebaek,et al.  Testicular germ cell cancer incidence in an immigration perspective, Denmark, 1978 to 2003. , 2010, The Journal of urology.

[13]  K. McGlynn,et al.  Etiologic factors in testicular germ-cell tumors. , 2009, Future oncology.

[14]  L. Richiardi,et al.  Does a testicular dysgenesis syndrome exist? , 2009, Human reproduction.

[15]  S. Chanock,et al.  Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes. , 2009, International journal of andrology.

[16]  N. Rothman,et al.  Prediagnostic Serum Concentrations of Organochlorine Compounds and Risk of Testicular Germ Cell Tumors , 2009, Environmental health perspectives.

[17]  B. Graubard,et al.  Polychlorinated biphenyls and risk of testicular germ cell tumors. , 2009, Cancer research.

[18]  R. Sharpe,et al.  Relationship between androgen action in the "male programming window," fetal sertoli cell number, and adult testis size in the rat. , 2008, Endocrinology.

[19]  S. Friis,et al.  Social inequality and incidence of and survival from male genital cancer in a population-based study in Denmark, 1994-2003. , 2008, European journal of cancer.

[20]  R. Sharpe "Additional" effects of phthalate mixtures on fetal testosterone production. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[21]  S. Schwartz,et al.  Serum Organochlorine Pesticide Residues and Risk of Testicular Germ Cell Carcinoma: A Population-Based Case-Control Study , 2008, Cancer Epidemiology Biomarkers & Prevention.

[22]  B. Graubard,et al.  Persistent organochlorine pesticides and risk of testicular germ cell tumors. , 2008, Journal of the National Cancer Institute.

[23]  Lee B. Smith,et al.  Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. , 2008, The Journal of clinical investigation.

[24]  D. Krewski,et al.  Testicular Cancer and Hormonally Active Agents , 2008, Journal of toxicology and environmental health. Part B, Critical reviews.

[25]  R. Motzer,et al.  Medical treatment of advanced testicular cancer. , 2008, JAMA.

[26]  Anna Oudin,et al.  Testicular cancer risk in first- and second-generation immigrants to Denmark. , 2008, Journal of the National Cancer Institute.

[27]  E. Rajpert-De Meyts,et al.  From Gonocytes to Testicular Cancer , 2007, Annals of the New York Academy of Sciences.

[28]  J. Auger,et al.  Environmental, occupational and familial risks for testicular cancer: a hospital-based case-control study. , 2007, International journal of andrology.

[29]  K. McGlynn,et al.  Trends in testicular germ cell tumours by ethnic group in the United States. , 2007, International journal of andrology.

[30]  P. Brochard,et al.  Brain tumours and exposure to pesticides: a case–control study in southwestern France , 2007, Occupational and Environmental Medicine.

[31]  M. Bates,et al.  Registry-based case-control study of cancer in California firefighters. , 2006, American journal of industrial medicine.

[32]  David J Lee,et al.  Cancer Incidence in Florida Professional Firefighters, 1981 to 1999 , 2006, Journal of occupational and environmental medicine.

[33]  G. K. Yamane Cancer incidence in the U.S. Air Force: 1989-2002. , 2006, Aviation, space, and environmental medicine.

[34]  E. R. Meyts Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects , 2006 .

[35]  F. Giordano,et al.  Endocrine-Disrupting Chemicals and Testicular Cancer: A Case-Control Study , 2006, Archives of environmental & occupational health.

[36]  M. Eriksson,et al.  In utero exposure to persistent organic pollutants in relation to testicular cancer risk. , 2006, International journal of andrology.

[37]  D. Krewski,et al.  Epidemiology of testicular cancer: An overview , 2005, International journal of cancer.

[38]  A. Sigurdson,et al.  International patterns and trends in testis cancer incidence , 2005, International journal of cancer.

[39]  R Y Ball,et al.  Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs , 2005 .

[40]  P. Kyyrönen,et al.  Testicular cancer, occupation and exposure to chemical agents among Finnish men in 1971–1995 , 2005, Cancer Causes & Control.

[41]  W. Ahrens,et al.  Residential exposure to overhead high-voltage lines and the risk of testicular cancer: results of a population-based case–control study in Hamburg (Germany) , 2005, International archives of occupational and environmental health.

[42]  I. Sesterhenn,et al.  World health organization classifications of tumours. pathology and genetics of tumours of the urinary system and male genital organs , 2005 .

[43]  P. Kyyrönen,et al.  Risk of esophageal, ovarian, testicular, kidney and bladder cancers and leukemia among finnish workers exposed to diesel or gasoline engine exhaust , 2004, International journal of cancer.

[44]  C. Ohlson,et al.  Testicular cancer and occupational exposure to polyvinyl chloride plastics: A case‐control study , 2004, International journal of cancer.

[45]  P. Gustavsson,et al.  Incidence of cancer among Swedish military and civil personnel involved in UN missions in the Balkans 1989–99 , 2004, Occupational and Environmental Medicine.

[46]  G. Samsa,et al.  Cancer Incidence Among Union Carpenters in New Jersey , 2003, Journal of occupational and environmental medicine.

[47]  K. Wiklund,et al.  Cancer risk in offspring of male pesticide applicators in agriculture in Sweden , 2003, Occupational and environmental medicine.

[48]  G. K. Yamane,et al.  Testicular carcinoma in U.S. Air Force aviators: a case-control study. , 2003, Aviation, space, and environmental medicine.

[49]  M. Hauptmann,et al.  Cancer incidence in the U.S. radiologic technologists health study, 1983–1998 , 2003 .

[50]  K. Torén,et al.  Testicular cancer among Swedish pulp and paper workers. , 2003, American journal of industrial medicine.

[51]  P. Sulem,et al.  Cancer incidence among Icelandic deck officers in a population-based study. , 2003, Scandinavian journal of work, environment & health.

[52]  W. Ahrens,et al.  Firefighting and risk of testicular cancer: results from a German population-based case-control study. , 2003, American journal of industrial medicine.

[53]  W. Ahrens,et al.  Testicular cancer and electromagnetic fields (EMF) in the workplace: results of a population-based case–control study in Germany , 2002, Cancer Causes & Control.

[54]  K. Hemminki,et al.  Cancer risks in Nordic immigrants and their offspring in Sweden. , 2002, European journal of cancer.

[55]  M. Hauptmann,et al.  Cancer incidence in the US radiologic technologists health study, 1983-1998. , 2002, Cancer.

[56]  A. Olshan,et al.  Occupational exposure assessment in case–control studies: opportunities for improvement , 2002, Occupational and environmental medicine.

[57]  M. Pollán,et al.  Incidence of testicular cancer and occupation among Swedish men gainfully employed in 1970. , 2001, Annals of epidemiology.

[58]  M. Bates,et al.  Is testicular cancer an occupational disease of fire fighters? , 2001, American journal of industrial medicine.

[59]  N. Skakkebaek,et al.  Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects , 2001, Human reproduction.

[60]  N. Le,et al.  Cohort cancer incidence among pulp and paper mill workers in British Columbia. , 2001, Scandinavian journal of work, environment & health.

[61]  A. Andersen,et al.  Hormone-dependent cancer and adverse reproductive outcomes in farmers' families--effects of climatic conditions favoring fungal growth in grain. , 2000, Scandinavian journal of work, environment & health.

[62]  L Hardell,et al.  Testicular cancer and occupational exposures with a focus on xenoestrogens in polyvinyl chloride plastics. , 2000, Chemosphere.

[63]  A. Andersen,et al.  Incidence of cancer among workers exposed to vinyl chloride in polyvinyl chloride manufacture , 2000, Occupational and environmental medicine.

[64]  Birgitta Floderus,et al.  Occupational magnetic field exposure and site-specific cancer incidence: a Swedish cohort study , 1999, Cancer Causes & Control.

[65]  J. Hansen Risk for testicular cancer after occupational exposure to plastics , 1999, International journal of cancer.

[66]  D. Thelle,et al.  Study of cancer incidence among 8530 male workers in eight Norwegian plants producing ferrosilicon and silicon metal. , 1999, Occupational and Environmental Medicine.

[67]  R. Sijmons,et al.  Geographic clustering of testicular cancer incidence in the northern part of The Netherlands , 1999, British Journal of Cancer.

[68]  D. Dimitrov,et al.  Cancer incidence in Republic of Bulgaria aircrew, 1964-1994. , 1999, Aviation, space, and environmental medicine.

[69]  L. Fleming,et al.  Cancer incidence in a cohort of licensed pesticide applicators in Florida. , 1999, Journal of occupational and environmental medicine.

[70]  J. Knoke,et al.  Testicular Cancer and Persian Gulf War Service , 1998, Epidemiology.

[71]  P. Mills Correlation analysis of pesticide use data and cancer incidence rates in California counties. , 1998, Archives of environmental health.

[72]  J. Newell,et al.  Incidence and occupational pattern of leukaemias, lymphomas, and testicular tumours in western Ireland over an 11 year period. , 1998, Journal of epidemiology and community health.

[73]  M M Finkelstein,et al.  Cancer incidence among Ontario police officers. , 1998, American journal of industrial medicine.

[74]  R. Pethybridge,et al.  Is testicular cancer an occupational disease? A case-control study of Royal Naval personnel. , 1997, Journal of the Royal Naval Medical Service.

[75]  J. Knight,et al.  Parental occupational exposure and the risk of testicular cancer in Ontario. , 1997, Journal of occupational and environmental medicine.

[76]  Birgitta Floderus,et al.  Occupational exposure to magnetic fields in relation to male breast cancer and testicular cancer: a Swedish case-control study , 1997, Cancer Causes & Control.

[77]  H. Møller Work in agriculture, childhood residence, nitrate exposure, and testicular cancer risk: a case-control study in Denmark. , 1997, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[78]  A. Skytthe,et al.  Cancer incidence among mild steel and stainless steel welders and other metal workers. , 1996, American journal of industrial medicine.

[79]  H. Weir,et al.  Occupation and risk of germ cell testicular cancer by histologic type in Ontario. , 1996, Journal of occupational and environmental medicine.

[80]  K. Wiklund,et al.  Testicular cancer in pesticide applicators in Swedish agriculture. , 1996, Scandinavian journal of work, environment & health.

[81]  Grayson Jk,et al.  Cancer incidence in United States Air Force aircrew, 1975-89. , 1996 .

[82]  M. Mahoney,et al.  The incidence of testicular cancer in Royal Air Force personnel. , 1995, British journal of urology.

[83]  W. Rhomberg,et al.  High frequency of metalworkers among patients with seminomatous tumors of the testis: a case-control study. , 1995, American journal of industrial medicine.

[84]  R. Davis,et al.  Cluster of testicular cancer in police officers exposed to hand-held radar. , 1993, American journal of industrial medicine.

[85]  T. Tynes,et al.  Incidence of cancer in Norwegian workers potentially exposed to electromagnetic fields. , 1992, American journal of epidemiology.

[86]  R. Hoover,et al.  Service in Vietnam and risk of testicular cancer. , 1991, Journal of the National Cancer Institute.

[87]  S. Huttly,et al.  Cancer of the testis, socioeconomic status, and occupation. , 1991, British journal of industrial medicine.

[88]  R. Hayes,et al.  Occupation and risk for testicular cancer: a case-control study. , 1990, International journal of epidemiology.

[89]  P. Nasca,et al.  Investigation of a testicular cancer cluster using a case-control approach. , 1990, International journal of epidemiology.

[90]  P. Mills,et al.  TESTICULAR CANCER ASSOCIATED WITH EMPLOYMENT IN AGRICULTURE AND OIL AND NATURAL GAS EXTRACTION , 1984, The Lancet.

[91]  J. Doar,et al.  Investigation and treatment of endocrinological disorders. , 1972, Lancet.

[92]  M. Joffe Reproduction and Adaptation: Genetic damage and male reproduction , 2011 .

[93]  E. Rajpert-De Meyts Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects. , 2006, Human reproduction update.

[94]  Jane A Hoppin,et al.  Cancer incidence in the agricultural health study. , 2005, Scandinavian journal of work, environment & health.

[95]  S. Koifman,et al.  Human reproductive system disturbances and pesticide exposure in Brazil. , 2002, Cadernos de saude publica.

[96]  E. Villadsen,et al.  Hodgkin's disease, pharyngeal cancer, and soft tissue sarcomas in Danish paper mill workers. , 1998, Journal of occupational and environmental medicine.

[97]  Crawford Pi,et al.  Is testicular cancer an occupational disease? A case-control study of Royal Naval personnel. , 1997 .

[98]  A. Andersen,et al.  Testicular cancer and parental use of fertilizers in agriculture. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[99]  T. J. Lyons,et al.  Cancer incidence in United States Air Force aircrew, 1975-89. , 1996, Aviation, space, and environmental medicine.

[100]  J. Vena,et al.  Occupational exposure to extreme temperature and risk of testicular cancer. , 1995, Archives of environmental health.

[101]  T. Bullman,et al.  Risk of testicular cancer associated with surrogate measures of Agent Orange exposure among Vietnam veterans on the Agent Orange Registry. , 1994, Annals of epidemiology.

[102]  A. Andersen,et al.  Incidence of cancer among nitrate fertilizer workers , 1994, International archives of occupational and environmental health.

[103]  M. Staples,et al.  Cancer incidence in Melbourne Metropolitan Fire Brigade members, 1980-1989. , 1993, Health reports.

[104]  R. Hayes,et al.  Testicular cancer in young men and parental occupational exposure. , 1991, American journal of industrial medicine.

[105]  S. K. Van Den Eeden,et al.  Occupation and the occurrence of testicular cancer. , 1991, American journal of industrial medicine.