European Urology

2. Patients and methods

The Swedish Family-Cancer Database was created in the 1990s by linking information from the Multigeneration Register, national censuses, Swedish Cancer Registry, and death notifications [10] x K. Hemminki, X. Li, K. Plna, C. Granstrom, P. Vaittinen. The nation-wide Swedish family-cancer database—updated structure and familial rates. Acta Oncol. 2001;40:772-777 . Data on family relationships were obtained from the Multigeneration Register, in which children born in 1932 and later are registered with their biological parents as families. Thus the individuals in the database can be divided into the offspring generation (individuals born in 1932 and later) and the parental generation. The Swedish Cancer Registry is based on compulsory reports of diagnosed cases, with coverage of the cancer registration close to 100% [11] x Centre for Epidemiology. Cancer incidence in Sweden 2006. Stockholm, Sweden: National Board of Health and Welfare, 2007. . Cases are reported separately by clinicians and pathologists/cytologists; information on cancers based on death certificates is not used. The underlying cause of death was available from the Swedish Causes of Death Register. The 2008 update of the database includes >11.8 million individuals and their cancers from 1958 to 2006 [12] x K. Hemminki, J. Ji, A. Brandt, S.M. Mousavi, J. Sundquist. The Swedish Family-Cancer Database 2009: prospects for histology-specific and immigrant studies. Int J Cancer. 2009;126:2259-2267 . Our study population comprised 3.9 million men from the offspring generation of the database with linkage to both parents. Most men without identified parents (approximately 850 000) were immigrants. The age structure of the database (offspring born after 1932) implies that the maximum age of diagnosis in the offspring generation was 74 yr. The age at diagnosis in the parental generation was not limited. Tumour characteristics have been available since 2002 according to the TNM system introduced by the American Joint Committee on Cancer [13] x S.R. Hamilton, L.A. Aaltonen (Eds.) Pathology and genetics of tumours of the digestive system. World Health Organization Classification of Tumours (International Agency for Research on Cancer, Lyon, France, 2000) . However, only T was useful for the present study because of the abundance of missing information for N and M.

Men in the offspring generation of the database were classified according to number, type, and diagnostic age of affected first-degree relatives (father or brother). Hazard ratios (HRs) of diagnosis with PCa and PCa-specific mortality were estimated using Cox regression; the HR can be interpreted as an estimate of the relative risk [14] x T.M. Therneau, P.M. Grambsch. Modeling survival data: extending the Cox model. (Springer, New York, NY, 2000) (“PROC PHREG”; SAS v.9.1; SAS Institute, Cary, NC, USA). Age-specific HRs were calculated using time-dependent variables. Individuals entered the risk period at birth, immigration date, or first year of the study (1961). The first year of the study was set as 1961 because of lower data quality between 1958 and 1960. For the analysis of incident PCa, censoring events were death; emigration; December 31, 2006; absence at census; and diagnosis of malignancy at sites other than prostate. Men were also censored at diagnosis of malignancy at sites other than prostate because their subsequent risk might be different from the risk of the general population. Men absent at census were censored because they were probably not living in Sweden anymore. For the analysis of death from PCa, censoring events were emigration; December 31, 2006; absence at census; and death from a cause other than PCa. Socioeconomic status, calendar period, and region were taken into account as covariates.

The Swedish Family-Cancer Database was approved by the Lund regional ethical committee on August 12, 2008 (No. 409/2008), with complementary approvals dated September 1, 2009, and January 22, 2010.