A compendium of familial relative risks of cancer among first degree relatives: A population-based study
Corresponding Author
Maurice P. Zeegers
Unit of Genetic Epidemiology, Department of Public Health and Epidemiology, School of Medicine, The University of Birmingham, Public Health Building, Edgbaston, Birmingham, United Kingdom
Cluster of Genetics and Cell Biology, Department of Complex Genetics, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands
Fax: +44-121-4142528
Department of Public Health and Epidemiology, Unit Of Genetic Epidemiology, University Of Birmingham, Public Health Building, Edgbaston, Birmingham, B15 2TT, UKSearch for more papers by this authorLeo J. Schouten
Department of Epidemiology, Research Institute for Growth and Development (GROW), Maastricht University, Maastricht, The Netherlands
Search for more papers by this authorR. Alexandra Goldbohm
TNO Quality of Life, Business Unit Prevention and Care, Leiden, The Netherlands
Search for more papers by this authorPiet A. van den Brandt
Department of Epidemiology, Research Institute for Growth and Development (GROW), Maastricht University, Maastricht, The Netherlands
Search for more papers by this authorCorresponding Author
Maurice P. Zeegers
Unit of Genetic Epidemiology, Department of Public Health and Epidemiology, School of Medicine, The University of Birmingham, Public Health Building, Edgbaston, Birmingham, United Kingdom
Cluster of Genetics and Cell Biology, Department of Complex Genetics, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands
Fax: +44-121-4142528
Department of Public Health and Epidemiology, Unit Of Genetic Epidemiology, University Of Birmingham, Public Health Building, Edgbaston, Birmingham, B15 2TT, UKSearch for more papers by this authorLeo J. Schouten
Department of Epidemiology, Research Institute for Growth and Development (GROW), Maastricht University, Maastricht, The Netherlands
Search for more papers by this authorR. Alexandra Goldbohm
TNO Quality of Life, Business Unit Prevention and Care, Leiden, The Netherlands
Search for more papers by this authorPiet A. van den Brandt
Department of Epidemiology, Research Institute for Growth and Development (GROW), Maastricht University, Maastricht, The Netherlands
Search for more papers by this authorAbstract
Familial clustering of cancer is expected to occur at practically all anatomical sites. However, few studies have had sufficient size to investigate different sites simultaneously and with adjustment for confounders. We evaluated familial clustering in the Netherlands Cohort Study in which 120,852 men and women, aged 55–69 years in 1986 were followed up for 13.3 years. 14,025 Probands, 6,629 parents and 4,271 siblings were diagnosed with cancer. Relative Risks (RR) of cancer in first degree family members were calculated by using multivariable Cox regression analyses. We also calculated false-positive reporting probabilities. Significant concordant familial clustering was observed for stomach (RRfather = 1.89, RRparent = 1.66, RRsister = 3.33, RRsibling = 2.38, RR1st degree = 1.69), colon/rectum (RRfather = 1.82, RRmother = 1.83, RRparent = 1.88, RR1st degree = 1.56), lung (RRbrother = 1.50) and breast cancer (RRmother = 1.65, RRsister = 1.72, RR1st degree = 1.72) with low false-positive reporting probabilities. Significant discordant familial clustering has been observed for combinations of pancreas-colon/rectum (RRmother = 2.42, RRparent = 1.89, RR1st degree = 1.73), larynx-lung (RRfather = 3.35, RRparent = 2.84, RR1st degree = 2.30), lung-oesophagus (RRsibling = 3.49), breast-bladder (RRfather = 2.79, RRparent = 2.61), endometrium-stomach (RRmother = 2.32), ovarium-oesophagus (RR1stdegree = 4.19), prostate-colon/rectum (RRparent = 1.46) and bladder-larynx/pharynx (RRfather = 2.49) cancer, although false-positive reporting probabilities were higher for these associations. Familial clustering of cancer occurs at most sites but is generally modest. Some observed discordant familial clustering is surprising but should be interpreted with caution as their prior probability is low. © 2008 Wiley-Liss, Inc.
References
- 1 Cannon-Albright LA,Thomas A,Goldgar DE,Gholami K,Rowe K,Jacobsen M,McWhorter WP,Skolnick MH. Familiality of cancer in Utah. Cancer Res 1994; 54: 2378–85.
- 2 Goldgar DE,Easton DF,Cannon-Albright LA,Skolnick MH. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst 1994; 86: 1600–8.
- 3
Vaittinen P,Hemminki K.
Familial cancer risks in offspring from discordant parental cancers.
Int J Cancer
1999;
81:
12–19.
10.1002/(SICI)1097-0215(19990331)81:1<12::AID-IJC3>3.0.CO;2-0 CAS PubMed Web of Science® Google Scholar
- 4 Hemminki K,Vaittinen P. Effect of paternal and maternal cancer on cancer in the offspring: a population-based study. Cancer. Epidemiol Biomarkers Prev 1997; 6: 993–7.
- 5 Sinilnikova OM,Mazoyer S,Bonnardel C,Lynch HT,Narod SA,Lenoir GM. BRCA1 and BRCA2 mutations in breast and ovarian cancer syndrome: reflection on the Creighton University historical series of high risk families. Fam Cancer 2006; 5: 15–20.
- 6 van Houwelingen KP,van Dijk BA,Hulsbergen-van de Kaa CA,Schouten LJ,Gorissen HJ,Schalken JA,van den Brandt PA,Oosterwijk E. Prevalence of von Hippel-Lindau gene mutations in sporadic renal cell carcinoma: results from The Netherlands cohort study. BMC Cancer 2005; 5: 57.
- 7 Lorenzo Bermejo J,Hemminki K. Familial lung cancer and aggregation of smoking habits: a simulation of the effect of shared environmental factors on the familial risk of cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 1738–40.
- 8
Verkasalo PK,Kaprio J,Koskenvuo M,Pukkala E.
Genetic predisposition, environment and cancer incidence: a nationwide twin study in Finland, 1976–1995.
Int J Cancer
1999;
83:
743–9.
10.1002/(SICI)1097-0215(19991210)83:6<743::AID-IJC8>3.0.CO;2-Q CAS PubMed Web of Science® Google Scholar
- 9
Dong C,Hemminki K.
Modification of cancer risks in offspring by sibling and parental cancers from 2,112,616 nuclear families.
Int J Cancer
2001;
92:
144–50.
10.1002/1097-0215(200102)9999:9999<::AID-IJC1147>3.0.CO;2-C CAS PubMed Web of Science® Google Scholar
- 10 Risch N. The genetic epidemiology of cancer: interpreting family and twin studies and their implication for molecular genetic approaches. Cancer Epidemiol Biomarkers Prev 2001; 10: 733–41.
- 11 Olsen JH,Boice JD,Jr,Seersholm N,Bautz A,Fraumeni JF,Jr. Cancer in the parents of children with cancer. N Engl J Med 1995; 333: 1594–9.
- 12
Carstensen B,Soll-Johanning H,Villadsen E,Sondergaard JO,Lynge E.
Familial aggregation of colorectal cancer in the general population.
Int J Cancer
1996;
68:
428–35.
10.1002/(SICI)1097-0215(19961115)68:4<428::AID-IJC5>3.0.CO;2-2 CAS PubMed Web of Science® Google Scholar
- 13 Tulinius H,Egilsson V,Olafsdottir GH,Sigvaldason H. Risk of prostate, ovarian, and endometrial cancer among relatives of women with breast cancer. BMJ 1992; 305: 855–7.
- 14 Hemminki K,Li X. Gender effects in familial cancer. Int J Cancer 2002; 102: 184–7.
- 15 Hemminki K,Li X. Familial risk of cancer by site and histopathology. Int J Cancer 2003; 103: 105–9.
- 16 Hemminki K,Li X. Familial risks of cancer as a guide to gene identification and mode of inheritance. Int J Cancer 2004; 110: 291–4.
- 17 Hemminki K,Li X,Czene K. Familial risk of cancer: data for clinical counseling and cancer genetics. Int J Cancer 2004; 108: 109–14.
- 18 van den Brandt PA,Goldbohm RA,van het Veer PAV,Hermus RJJ,Sturmans F. A large-scale prospective cohort study on diet and cancer in the Netherlands. J Clin Epidemiol 1990; 43: 285–95.
- 19 van den Brandt PA,Schouten LJ,Goldbohm RA,Dorant E,Hunen PHM. Development of a record linkage protocol for use in the Dutch cancer registry for epidemiological research. Int J Epidemiol 1990; 19: 553–8.
- 20 Goldbohm RA,van den Brandt PA,Brants HA,van't Veer P,Al M,Sturmans F,Hermus RJ. Validation of a dietary questionnaire used in a large-scale prospective cohort study on diet and cancer. Eur J Clin Nutr 1994; 48: 253–65.
- 21 World Health Organization. Manual of the international statistical classification of diseases, injuries, and causes of death: based on the recommendations of the ninth revision conference. Geneva: World Health Organization, 1975.
- 22 Cox D. Regression models and life-tables. J Roy Statist Soc Ser B Method 1972; 34: 187–220.
- 23 Lin DY,Ying Z. Cox regression with incomplete covariate measurements. JASA 1993; 88: 1341–9.
- 24 Schoenfeld D. Partial residuals for the proportional hazards regression model. Biometrika 1982; 69: 239–41.
- 25 Yasui Y,Newcomb PA,Trentham-Dietz A,Egan KM. Familial relative risk estimates for use in epidemiologic analyses. Am J Epidemiol 2006; 164: 697–705.
- 26 Wacholder S,Chanock S,Garcia-Closas M,El Ghormli L,Rothman N. Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst 2004; 96: 434–42.
- 27
Khoury M,Beaty T,Cohen B.
Fundamentals of genetic epidemiology.
New York:
Oxford University Press,
1993.
10.1093/oso/9780195052886.001.0001 Google Scholar
- 28 Schouten LJ,De Rijke JM,Huveneers JAM,Jager JJ,Van den Brandt PA. 10 year cancer incidence in Mid and South Limburg, The Netherlands. Maastricht. Integraal Kankercentrum Limburg, 1998.
- 29 Visser O,Coebergh JWW,Schouten LJ,Van Dijck JAAM. Incidence of cancer in the Netherlands 1994. Sixth Report of the Netherlands Cancer Registry, vol. Vereniging Integrale Kankercentra Utrecht, 1997.
- 30 Watson P,Vasen HF,Mecklin JP,Jarvinen H,Lynch HT. The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer. Am J Med 1994; 96: 516–20.
- 31 Croce A,Neri G,Moretti A,Bianchedi M. [Multiple primary malignant tumors of the larynx and lung.] G Chir 1993; 14: 354–8.
- 32 Sellers TA,Ooi WL,Elston RC,Chen VW,Bailey-Wilson JE,Rothschild H. Increased familial risk for non-lung cancer among relatives of lung cancer patients. Am J Epidemiol 1987; 126: 237–46.
- 33 Tokuhata GK,Lilienfeld AM. Familial aggregation of lung cancer in humans. J Natl Cancer Inst 1963; 30: 289–312.
- 34 Wu PF,Lee CH,Wang MJ,Goggins WB,Chiang TA,Huang MS,Ko YC. Cancer aggregation and complex segregation analysis of families with female non-smoking lung cancer probands in Taiwan. Eur J Cancer 2004; 40: 260–6.
- 35 Wunsch-Filho V,Boffetta P,Colin D,Moncau JE. Familial cancer aggregation and the risk of lung cancer. Sao Paulo Med J 2002; 120: 38–44.
- 36
Sellers TA,Elston RC,Atwood LD,Rothschild H.
Lung cancer histologic type and family history of cancer.
Cancer
1992;
69:
86–91.
10.1002/1097-0142(19920101)69:1<86::AID-CNCR2820690116>3.0.CO;2-S CAS PubMed Web of Science® Google Scholar
- 37 Etzel CJ,Amos CI,Spitz MR. Risk for smoking-related cancer among relatives of lung cancer patients. Cancer Res 2003; 63: 8531–5.
- 38 Shaw GL,Falk RT,Pickle LW,Mason TJ,Buffler PA. Lung cancer risk associated with cancer in relatives. J Clin Epidemiol 1991; 44: 429–37.
- 39
Ambrosone CB,Rao U,Michalek AM,Cummings KM,Mettlin CJ.
Lung cancer histologic types and family history of cancer. Analysis of histologic subtypes of 872 patients with primary lung cancer.
Cancer
1993;
72:
1192–8.
10.1002/1097-0142(19930815)72:4<1192::AID-CNCR2820720410>3.0.CO;2-S CAS PubMed Web of Science® Google Scholar
- 40 Li X,Hemminki K. Inherited predisposition to early onset lung cancer according to histological type. Int J Cancer 2004; 112: 451–7.
- 41 Schwartz AG,Ruckdeschel JC. Familial lung cancer: genetic susceptibility and relationship to chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006; 173: 16–22.
- 42 Bailey-Wilson JE,Amos CI,Pinney SM,Petersen GM,de Andrade M,Wiest JS,Fain P,Schwartz AG,You M,Franklin W,Klein C,Gazdar A, et al. A major lung cancer susceptibility locus maps to chromosome 6q23–25. Am J Hum Genet 2004; 75: 460–74.
- 43
Pharoah PD,Day NE,Duffy S,Easton DF,Ponder BA.
Family history and the risk of breast cancer: a systematic review and meta-analysis.
Int J Cancer
1997;
71:
800–9.
10.1002/(SICI)1097-0215(19970529)71:5<800::AID-IJC18>3.0.CO;2-B CAS PubMed Web of Science® Google Scholar
- 44 Collaborative Group. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 2001; 358: 1389–99.
- 45 Hemminki K,Granstrom C. Familial clustering of ovarian and endometrial cancers. Eur J Cancer 2004; 40: 90–5.
- 46 Antoniou A,Pharoah PD,Narod S,Risch HA,Eyfjord JE,Hopper JL,Loman N,Olsson H,Johannsson O,Borg A,Pasini B,Radice P, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 2003; 72: 1117–30.
- 47 Zeegers MP,Jellema A,Ostrer H. Empiric risk of prostate carcinoma for relatives of patients with prostate carcinoma: a meta-analysis. Cancer 2003; 97: 1894–903.
- 48 Verhage BA,Kiemeney LA. Genetic susceptibility to prostate cancer: a review. Fam Cancer 2003; 2: 57–67.
- 49 Nascimento CM,Schmitz-Dräger BJ,Zeegers M,Steineck G,Kogevinas M,Real FX,Malats N. Epidemiology of urinary bladder cancer: from tumor development to patient's death. World J Urol 2007; 25: 285–95.
- 50 Kantor AF,Hartge P,Hoover RN,Fraumeni JF,Jr. Familial and environmental interactions in bladder cancer risk. Int J Cancer 1985; 35: 703–6.
- 51 Plna K,Hemminki K. Familial bladder cancer in the National Swedish Family Cancer Database. J Urol 2001; 166: 2129–33.
- 52 Aben KK,Witjes JA,Schoenberg MP,Hulsbergen-van de Kaa C,Verbeek AL,Kiemeney LA. Familial aggregation of urothelial cell carcinoma. Int J Cancer 2002; 98: 274–8.
- 53 Gago-Dominguez M,Yuan JM,Castelao JE,Ross RK,Yu MC. Family history and risk of renal cell carcinoma. Cancer Epidemiol Biomarkers Prev 2001; 10: 1001–4.
- 54
Schlehofer B,Pommer W,Mellemgaard A,Stewart JH,McCredie M,Niwa S,Lindblad P,Mandel JS,McLaughlin JK,Wahrendorf J.
International renal-cell-cancer study VI. The role of medical and family history.
Int J Cancer
1996;
66:
723–6.
10.1002/(SICI)1097-0215(19960611)66:6<723::AID-IJC2>3.0.CO;2-1 CAS PubMed Web of Science® Google Scholar
- 55 Czene K,Hemminki K. Kidney cancer in the Swedish Family Cancer Database: familial risks and second primary malignancies. Kidney Int 2002; 61: 1806–13.
- 56 Hemminki K,Li X. Age-specific familial risks for renal cell carcinoma with evidence on recessive heritable effects. Kidney Int 2004; 65: 2298–302.
- 57 Ziogas A,Anton-Culver H. Validation of family history data in cancer family registries. Am J Prev Med 2003; 24: 190–8.
- 58 Kerber RA,Slattery ML. Comparison of self-reported and database-linked family history of cancer data in a case-control study. Am J Epidemiol 1997; 146: 244–8.