E p i d e m i o l o g y 998 Familial risk of colorectal adenoma E Hiripi et al affected by cancer/adenoma with adenoma incidence in the general population. Cases of adenoma and person – years were classified according to gender, family history of cancer, calendar year and age. The distribution of the number of cases in each group was modelled by Poisson’s regression. The Genmod procedure of the SAS software was used for the analysis (SAS Version 9.1; SAS Institute, Cary, NC, USA). RESULTS The Database included 2943 individuals diagnosed with colorectal adenoma and with information about both parents. The parental generation incorporated 12 458 individuals with colorectal adeno- ma. The incidence of colorectal adenoma in Sweden has been increasing since the 1960s; the site-specific age-adjusted incidence rates for 1990 – 1999 and 2000 – 2004 are displayed in Table 1. Table 2 shows some demographic characteristics and RRs. Women were at a slightly lower risk of colorectal adenoma compared to men (RR ¼ 0.89; 95% CI ¼ 0.82 – 0.94). As expected, age was associated with risk, which was also increased with a family history of CRC (RR ¼ 2.72; 95% CI ¼ 2.46 – 3.00) and particularly of colorectal adenoma (RR ¼ 4.99; 95% CI ¼ 4.12 – 6.05). Among the 108 patients with colorectal adenoma and also a family history of this, 55 individuals (in 27 families) had an affected sibling (RR ¼ 9.41; 95% CI ¼ 7.21 – 12.3). Standard Poisson’s regression assumes independent observa- tions. Because of possible overdispersion due to clustered family 2 structure, s.e. were adjusted using Pearson’s w , divided by the degrees of freedom, resulting in slightly wider CIs. For example, the RR of colorectal adenoma for individuals with a positive family history was 4.99 (95% CI ¼ 3.36 – 7.41). However, as this procedure may be sensitive to outlying observations to be expected in our large data set, we show unadjusted CIs and point out the possibly conservative limits due to familial dependence. The left column of Table 3 shows colorectal adenoma RRs according to parental history of CRC and colorectal adenoma: it was increased among offspring of patients with colon cancer (RR ¼ 2.59; 95% CI ¼ 2.28 – 2.94), rectal cancer (RR ¼ 2.59; 95% CI ¼ 2.20 – 3.05), colon adenoma (RR ¼ 4.43; 95% CI ¼ 3.09 – 6.34), and rectal adenoma (RR ¼ 2.62; 95% CI ¼ 1.77 – 3.89). Correspond- ing risks with a sibling history of CRC and colorectal adenoma are displayed in the right column of Table 3, with particularly high risks when a sibling had colon (RR ¼ 11.3; 95% CI ¼ 8.15 – 15.7) or rectal adenoma (RR ¼ 6.94; 95% CI ¼ 4.42 – 10.9). Colorectal adenoma was higher for the offspring of individuals with colon adenoma (RR ¼ 4.43) than those with colon cancer (RR ¼ 2.59; P-value o0.01). It was also higher for those with a sibling with colon adenoma (RR ¼ 11.3) than when a sibling had colon cancer (RR ¼ 2.64; P-value o0.01). Colorectal adenoma risk was higher when a sibling had rectal adenoma (RR ¼ 6.94), than when a sibling had rectal cancer (RR ¼ 2.75; P-value o0.01). The offspring risk of colorectal adenoma was higher when parents had multiple adenomas than when parents presented with single adenomas (RR ¼ 21.6; 95% CI ¼ 5.70 – 82.0). Sibling risk was also significantly higher for multiple than for single adenomas in any colorectal site (RR ¼ 20.7; 95% CI ¼ 3.48 – 123) (results not shown). Table 4 shows colorectal adenoma RRs with a family history of malignancies other than CRC, but only for sites where at least 10 individuals with a family history of cancer had colorectal adenoma. The risk was increased among the offspring of parents with leukaemia (RR ¼ 1.34; 95% CI ¼ 1.02 – 1.76). Among the 53 affected parents, 17 had chronic lymphoblastic, 14 acute myeloid, 5 acute lymphoblastic (ALL), 2 chronic myeloid leukaemias; 7 type unspecified; 8 polycythaemia vera. Colorectal adenoma risk was the highest among the offspring of the five patients with ALL (RR ¼ 3.38; 95% CI ¼ 1.41 – 8.14) in which the leukaemias were British Journal of Cancer (2008) 98(5), 997 – 1000 Table 1 Age standardised incidence of colorectal adenoma/100 000 person-years diagnosed in Sweden between 1990 and 2004 (adjusted to world standard population 2000) 1990 – 1999 2000 – 2004 Table 2 Relative risk of colorectal adenoma according to sex, age, calendar year, and family history of colorectal cancer/adenoma Site Colorectum Colon Ascending Transverse Descending Sigmoid Other Multiple Rectum Covariate Gender Age of diagnosis Calendar year of diagnosis Family history of colorectal cancer Family history of colorectal adenoma Bold signifies Po0.05. Location in parent/sibling Invasive cancer Colon Rectum Adenoma Colon Rectum Bold signifies Po0.05. 5.03 2.89 0.52 0.31 0.16 1.34 0.52 0.04 2.14 3.29 1.65 0.24 0.15 0.07 0.81 0.36 0.02 1.64 Level Females Males N 1365 1578 RR (95% CI) 0.89 (0.82 – 0.94) 1.00 (ref.) Before 50 706 0.03 (0.02 – 0.04) 50 – 54 449 0.26 (0.21 – 0.33) 55 – 59 628 0.49 (0.40 – 0.59) 60 and above 1160 1.00 (ref) Before 1980 1980 – 1989 1990 – 1999 2000 – 2004 Yes No Yes No 90 0.18 (0.11 – 0.28) 282 0.58 (0.43 – 0.78) 1038 0.67 (0.57 – 0.79) 1533 1.00 (ref.) 474 2.72 (2.46 – 3.00) 2469 1.00 (ref.) 108 4.99 (4.12 – 6.05) 2835 1.00 (ref.) Colorectal adenoma Offspring N RR (95% CI) 264 2.59 (2.28 – 2.94) 153 2.59 (2.20 – 3.05) 30 4.43 (3.09 – 6.34) 25 2.62 (1.77 – 3.89) Sibling N RR (95% CI) 50 2.64 (2.00 – 3.50) 33 2.75 (1.95 – 3.88) 36 11.3 (8.15 – 15.7) 19 6.94 (4.42 – 10.9) Table 3 Relative risk of colorectal adenoma for the offspring/sibling of individuals with colorectal cancer/adenoma diagnosed at advanced ages (63 – 94 years). Risk was also increased among the offspring of parents with acute myeloid leukaemia (RR ¼ 1.79; 95% CI ¼ 1.06 – 3.02). It was also increased among individuals with a parental history of stomach (RR ¼ 1.28; 95% & 2008 Cancer Research UK