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First degree relatives and familial aggregation of gastric cancer: who to choose for control in case–control studies?

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Abstract

Gastric carcinogenesis is a multifactorial process involving host gene and environmental interactions. Diverse case–control studies using different types of controls addressed the familial aggregation role for gastric cancer development. Our aim is to discuss the advantages and expected bias according to the different type of eligible controls. A PubMed search of papers on a query on first degree relatives of gastric cancer patients was conducted. The retrieved studies were evaluated regarding quality based on STROBE checklist. Data concerning risk of premalignant lesions and Helicobacter pylori infection was retrieved as the type of controls used on each study. Nine case–control studies were selected. A variety of controls were used ranging from general population to dyspeptic patients and spouses of the cases. We have observed that, independently of the type of control, the risk for the prevalence of premalignant lesions and H. pylori infection was higher for the cases. However, all of the evaluated case–control studies were average quality studies (mean 28 out of 45), with a small number of cases and controls (range from 39 to 300). Furthermore, concerning gene–environment interaction, each of the discussed type of control (general population, dyspeptic, spouse and neighbor) has potential advantages and disadvantages. The current data suggests that selection of any type of the aforementioned controls is feasible and seems to be mainly related to the feasibility of recruitment more than the genetic or environmental backgrounds. General population and dyspeptic patients would be equally appropriate for studies on familial aggregation of gastric cancer. Nevertheless, high-quality cohort studies are needed to validate this assumption.

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References

  1. Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24(14):2137–2150. doi:10.1200/JCO.2005.05.2308

    Article  PubMed  Google Scholar 

  2. Available at: http://globocan.iarc.fr/

  3. Hundahl SA, Menck HR, Mansour EG, Winchester DP (1997) The national cancer data base report on gastric carcinoma. Cancer 80(12):2333–2341. doi:10.1002/(SICI)1097-0142(19971215)80:12<2333:AID-CNCR15>3.0.CO;2-V

    Article  PubMed  CAS  Google Scholar 

  4. Kubota H, Kotoh T, Masunaga R, Dhar DK, Shibakita M, Tachibana M, Kohno H, Nagasue N (2000) Impact of screening survey of gastric cancer on clinicopathological features and survival: retrospective study at a single institution. Surgery 128(1):41–47. doi:10.1067/msy.2000.106812

    Article  PubMed  CAS  Google Scholar 

  5. Hisamichi S, Sugawara N, Fukao A (1988) Effectiveness of gastric mass screening in Japan. Cancer Detect Prev 11(3–6):323–329

    PubMed  CAS  Google Scholar 

  6. Dinis-Ribeiro M, da Costa-Pereira A, Lopes C, Moreira-Dias L (2007) Feasibility and cost-effectiveness of using magnification chromoendoscopy and pepsinogen serum levels for the follow-up of patients with atrophic chronic gastritis and intestinal metaplasia. J Gastroenterol Hepatol 22(10):1594–1604. doi:10.1111/j.1440-1746.2007.04863.x

    Article  PubMed  Google Scholar 

  7. de Vries AC, Haringsma J, Kuipers EJ (2007) The detection, surveillance and treatment of premalignant gastric lesions related to Helicobacter pylori infection. Helicobacter 12(1):1–15. doi:10.1111/j.1523-5378.2007.00475.x

    Article  PubMed  Google Scholar 

  8. Lauren P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 64:31–49

    PubMed  CAS  Google Scholar 

  9. Correa P, Houghton J (2007) Carcinogenesis of Helicobacter pylori. Gastroenterology 133(2):659–672. doi:10.1053/j.gastro.2007.06.026

    Article  PubMed  CAS  Google Scholar 

  10. Milne AN, Carneiro F, O’Morain C, Offerhaus GJ (2009) Nature meets nurture: molecular genetics of gastric cancer. Hum Genet 126(5):615–628. doi:10.1007/s00439-009-0722-x

    Article  PubMed  CAS  Google Scholar 

  11. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF Jr, Rabkin CS (2000) Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404(6776):398–402. doi:10.1038/35006081

    Article  PubMed  CAS  Google Scholar 

  12. Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, Capelinha AF, Quint W, Caldas C, van Doorn LJ, Carneiro F, Sobrinho-Simoes M (2002) Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 94(22):1680–1687

    Article  PubMed  CAS  Google Scholar 

  13. Machado JC, Figueiredo C, Canedo P, Pharoah P, Carvalho R, Nabais S, Castro Alves C, Campos ML, Van Doorn LJ, Caldas C, Seruca R, Carneiro F, Sobrinho-Simoes M (2003) A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology 125(2):364–371. doi:S0016508503008990

    Article  PubMed  CAS  Google Scholar 

  14. Peleteiro B, Lunet N, Carrilho C, Duraes C, Machado JC, La Vecchia C, Barros H (2010) Association between cytokine gene polymorphisms and gastric precancerous lesions: systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 19(3):762–776. doi:10.1158/1055-9965.EPI-09-0917

    Article  PubMed  CAS  Google Scholar 

  15. WCRF-AICR (2007) Food, nutrition, physical activity and the prevention of cancer: a global perspective. Washington

  16. Jenab M, McKay JD, Ferrari P, Biessy C, Laing S, Munar GM, Sala N, Pena S, Crusius JB, Overvad K, Jensen MK, Olsen A, Tjonneland A, Clavel-Chapelon F, Boutron-Ruault MC, Kaaks R, Linseisen J, Boeing H, Bergmann MM, Trichopoulou A, Georgila C, Psaltopoulou T, Mattiello A, Vineis P, Pala V, Palli D, Tumino R, Numans ME, Peeters PH, Bueno-de-Mesquita HB, Lund E, Ardanaz E, Sanchez MJ, Dorronsoro M, Sanchez CN, Quiros JR, Hallmans G, Stenling R, Manjer J, Regner S, Key T, Bingham S, Khaw KT, Slimani N, Rinaldi S, Boffetta P, Carneiro F, Riboli E, Gonzalez C (2008) CDH1 gene polymorphisms, smoking, Helicobacter pylori infection and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Eur J Cancer 44(6):774–780. doi:10.1016/j.ejca.2008.02.003

    Article  PubMed  CAS  Google Scholar 

  17. Pharoah PD, Guilford P, Caldas C (2001) Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology 121(6):1348–1353. doi:S0016508501595554

    Article  PubMed  CAS  Google Scholar 

  18. Fitzgerald RC, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V, Chung DC, Norton J, Ragunath K, Van Krieken JH, Dwerryhouse S, Caldas C (2010) Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 47(7):436–444. doi:10.1136/jmg.2009.074237

    Article  PubMed  CAS  Google Scholar 

  19. Capelle LG, Van Grieken NC, Lingsma HF, Steyerberg EW, Klokman WJ, Bruno MJ, Vasen HF, Kuipers EJ (2010) Risk and epidemiological time trends of gastric cancer in Lynch syndrome carriers in the Netherlands. Gastroenterology 138(2):487–492. doi:10.1053/j.gastro.2009.10.051

    Article  PubMed  Google Scholar 

  20. Watson P, Vasen HF, Mecklin JP, Bernstein I, Aarnio M, Jarvinen HJ, Myrhoj T, Sunde L, Wijnen JT, Lynch HT (2008) The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 123(2):444–449. doi:10.1002/ijc.23508

    Article  PubMed  CAS  Google Scholar 

  21. Rokkas T, Sechopoulos P, Pistiolas D, Margantinis G, Koukoulis G (2010) Helicobacter pylori infection and gastric histology in first-degree relatives of gastric cancer patients: a meta-analysis. Eur J Gastroenterol Hepatol 22(9):1128–1133. doi:10.1097/MEG.0b013e3283398d37

    Article  PubMed  Google Scholar 

  22. El-Omar EM, Oien K, Murray LS, El-Nujumi A, Wirz A, Gillen D, Williams C, Fullarton G, McColl KE (2000) Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori. Gastroenterology 118(1):22–30. doi:S0016508500390151

    Article  PubMed  CAS  Google Scholar 

  23. Eto K, Ohyama S, Yamaguchi T, Wada T, Suzuki Y, Mitsumori N, Kashiwagi H, Anazawa S, Yanaga K, Urashima M (2006) Familial clustering in subgroups of gastric cancer stratified by histology, age group and location. Eur J Surg Oncol 32(7):743–748. doi:10.1016/j.ejso.2006.04.005

    Article  PubMed  CAS  Google Scholar 

  24. Brenner H, Bode G, Boeing H (2000) Helicobacter pylori infection among offspring of patients with stomach cancer. Gastroenterology 118(1):31–35. doi:S0016508500783867

    Article  PubMed  CAS  Google Scholar 

  25. Chang YW, Han YS, Lee DK, Kim HJ, Lim HS, Moon JS, Dong SH, Kim BH, Lee JI, Chang R (2002) Role of Helicobacter pylori infection among offspring or siblings of gastric cancer patients. Int J Cancer 101(5):469–474. doi:10.1002/ijc.10637

    Article  PubMed  CAS  Google Scholar 

  26. Sheu BS, Yang HB, Sheu SM, Huang AH, Wu JJ (2003) Higher gastric cycloxygenase-2 expression and precancerous change in Helicobacter pylori-infected relatives of gastric cancer patients. Clin Cancer Res 9(14):5245–5251

    PubMed  CAS  Google Scholar 

  27. Carneiro F, Taveira-Gomes A, Cabral-Correia A, Vasconcelos-Teixeira A, Barreira R, Cardoso-Oliveira M, Sobrinho-Simoes M (1993) Characteristics of the gastric mucosa of direct relatives of patients with sporadic gastric carcinoma. Eur J Cancer Prev 2(3):239–246

    Article  PubMed  CAS  Google Scholar 

  28. Leung WK, Ng EK, Lam CC, Chan KF, Chan WY, Auyeung AC, Wu JC, Ching JY, Lau JY, Sung JJ (2006) Helicobacter pylori infection in 1st degree relatives of Chinese gastric cancer patients. Scand J Gastroenterol 41(3):274–279. doi:10.1080/00365520510024269

    Article  PubMed  Google Scholar 

  29. Jablonska M, Chlumska A (2001) Genetic factors in the development of gastric precancerous lesions—a role of Helicobacter pylori ? J Physiol Paris 95(1–6):477–481. doi:S0928-4257(01)00066-3

    Article  PubMed  CAS  Google Scholar 

  30. Motta CR, Cunha MP, Queiroz DM, Cruz FW, Guerra EJ, Mota RM, Braga LL (2008) Gastric precancerous lesions and Helicobacter pylori infection in relatives of gastric cancer patients from Northeastern Brazil. Digestion 78(1):3–8. doi:10.1159/000151297

    Article  PubMed  Google Scholar 

  31. Shin CM, Kim N, Yang HJ, Cho SI, Lee HS, Kim JS, Jung HC, Song IS (2010) Stomach cancer risk in gastric cancer relatives: interaction between Helicobacter pylori infection and family history of gastric cancer for the risk of stomach cancer. J Clin Gastroenterol 44(2):e34–e39. doi:10.1097/MCG.0b013e3181a159c4

    Article  PubMed  Google Scholar 

  32. Kaplan S, Novikov I, Modan B (1998) A methodological note on the selection of friends as controls. Int J Epidemiol 27(4):727–729

    Article  PubMed  CAS  Google Scholar 

  33. Wacholder S, McLaughlin JK, Silverman DT, Mandel JS (1992) Selection of controls in case–control studies. I. Principles. Am J Epidemiol 135(9):1019–1028

    PubMed  CAS  Google Scholar 

  34. Wacholder S, Silverman DT, McLaughlin JK, Mandel JS (1992) Selection of controls in case–control studies. II. Types of controls. Am J Epidemiol 135(9):1029–1041

    PubMed  CAS  Google Scholar 

  35. Perillo MG (1993) Choice of controls in case–control studies. J Manipulative Physiol Ther 16(9):578–585

    PubMed  CAS  Google Scholar 

  36. Grimes DA, Schulz KF (2005) Compared to what? Finding controls for case–control studies. Lancet 365(9468):1429–1433. doi:10.1016/S0140-6736(05)66379-9

    Article  PubMed  Google Scholar 

  37. Cassidy A, Myles JP, Duffy SW, Liloglou T, Field JK (2006) Family history and risk of lung cancer: age-at-diagnosis in cases and first-degree relatives. Br J Cancer 95(9):1288–1290. doi:10.1038/sj.bjc.6603386

    Article  PubMed  CAS  Google Scholar 

  38. Drossman DA (2006) The functional gastrointestinal disorders and the Rome III process. Gastroenterology 130(5):1377–1390. doi:10.1053/j.gastro.2006.03.008

    Article  PubMed  Google Scholar 

  39. Verhage BA, Aben KK, Straatman H, Verbeek AL, Beaty TH, Kiemeney LA (2003) Spouse controls in family case–control studies: a methodological consideration. Fam Cancer 2(2):101–108. doi:5144336

    Article  PubMed  Google Scholar 

  40. Lee WC, Chang CH (2006) Assessing effects of disease genes and gene-environment interactions: the case-spouse design and the counterfactual-control analysis. J Epidemiol Community Health 60(8):683–685. doi:10.1136/jech.2005.043554

    Article  PubMed  Google Scholar 

  41. Allison DB, Neale MC, Kezis MI, Alfonso VC, Heshka S, Heymsfield SB (1996) Assortative mating for relative weight: genetic implications. Behav Genet 26(2):103–111

    Article  PubMed  CAS  Google Scholar 

  42. Jefferies S, Goldgar D, Eeles R (2008) The accuracy of cancer diagnoses as reported in families with head and neck cancer: a case–control study. Clin Oncol (R Coll Radiol) 20(4):309–314. doi:10.1016/j.clon.2008.01.008

    Article  CAS  Google Scholar 

  43. Graham DY, Malaty HM, Evans DG, Evans DJ Jr, Klein PD, Adam E (1991) Epidemiology of Helicobacter pylori in an asymptomatic population in the United States. Effect of age, race, and socioeconomic status. Gastroenterology 100(6):1495–1501. doi:S001650859100197X

    PubMed  CAS  Google Scholar 

  44. Graham DY, Adam E, Reddy GT, Agarwal JP, Agarwal R, Evans DJ Jr, Malaty HM, Evans DG (1991) Seroepidemiology of Helicobacter pylori infection in India. Comparison of developing and developed countries. Dig Dis Sci 36(8):1084–1088

    Article  PubMed  CAS  Google Scholar 

  45. Brenner H, Weyermann M, Rothenbacher D (2006) Clustering of Helicobacter pylori infection in couples: differences between high- and low-prevalence population groups. Ann Epidemiol 16(7):516–520. doi:10.1016/j.annepidem.2005.09.009

    Article  PubMed  Google Scholar 

  46. Akcan Y, Ersan S, Alper M, Bicik Z, Aytug N (2000) The transmission of Helicobacter pylori via exposure to common sources outweighs the person-to-person contact among spouses in developing countries. Am J Gastroenterol 95(1):317–319. doi:10.1111/j.1572-0241.2000.01722.x

    Article  PubMed  CAS  Google Scholar 

  47. Luman W, Zhao Y, Ng HS, Ling KL (2002) Helicobacter pylori infection is unlikely to be transmitted between partners: evidence from genotypic study in partners of infected patients. Eur J Gastroenterol Hepatol 14(5):521–528

    Article  PubMed  CAS  Google Scholar 

  48. Suzuki J, Muraoka H, Kobayasi I, Fujita T, Mine T (1999) Rare incidence of interspousal transmission of Helicobacter pylori in asymptomatic individuals in Japan. J Clin Microbiol 37(12):4174–4176

    PubMed  CAS  Google Scholar 

  49. Vernick LJ, Vernick SL, Kuller LH (1984) Selection of neighborhood controls: logistics and fieldwork. J Chronic Dis 37(3):177–182

    Article  PubMed  CAS  Google Scholar 

  50. Soegaard M, Frederiksen K, Jensen A, Hogdall E, Hogdall C, Blaakaer J, Ramus SJ, Gayther SA, Kjaer SK (2009) Risk of ovarian cancer in women with first-degree relatives with cancer. Acta Obstet Gynecol Scand 88(4):449–456. doi:10.1080/00016340902807207

    Article  PubMed  Google Scholar 

  51. Delport W, Cunningham M, Olivier B, Preisig O, van der Merwe SW (2006) A population genetics pedigree perspective on the transmission of Helicobacter pylori. Genetics 174(4):2107–2118. doi:10.1534/genetics.106.057703

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Prof. Leonor David for helpful suggestions and discussion and to Dr. Sollari Allegro and Dr. Isabel Pedroto for the support. RMP acknowledges “ Fundação para a Ciência e a Tecnologia” for financial support (SFRH/SINTD/60034/2009) and Hospital Santo António for an research grant.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Biomedical Sciences, University of Porto (ICBAS/UP), Porto, Portugal

    Ricardo Marcos-Pinto, Celso A. Reis & Jorge Areias

  2. Department of Gastroenterology, Hospital Santo António, Porto, Portugal

    Ricardo Marcos-Pinto, José Ferreira & Jorge Areias

  3. Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal

    Ricardo Marcos-Pinto, Fátima Carneiro, José Carlos Machado, Ceu Figueiredo & Celso A. Reis

  4. Medical Faculty, University of Porto/CINTESIS, Porto, Portugal

    Ricardo Marcos-Pinto & Mário Dinis-Ribeiro

  5. Department of Pathological Anatomy, Medical Faculty, University of Porto, Porto, Portugal

    Fátima Carneiro, José Carlos Machado, Ceu Figueiredo & Celso A. Reis

  6. Department of Gastroenterology, Portuguese Oncology Institute, Porto, Portugal

    Mário Dinis-Ribeiro

  7. Department of Gastroenterology, Centro Hospitalar do Porto, Largo do Prof. Abel Salazar, 4099, Porto, Portugal

    Ricardo Marcos-Pinto

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  1. Ricardo Marcos-Pinto
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Marcos-Pinto, R., Dinis-Ribeiro, M., Carneiro, F. et al. First degree relatives and familial aggregation of gastric cancer: who to choose for control in case–control studies?. Familial Cancer 11, 137–143 (2012). https://doi.org/10.1007/s10689-011-9488-0

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