Table 4 Relative risk of colorectal adenoma for the offspring/siblings of individuals with invasive cancer Colorectal adenoma Cancer site in parent/sibling Tongue/mouth Stomach Liver Pancreas Lung Breast Cervix uteri Endometrium Ovary Prostate Kidney Urinary organs Melanoma Squamous cell skin Nervous system Endocrine glands Connective tissue Non-Hodgkin lymphoma Multiple myeloma Leukaemia Any cancer Bold signifies Po0.05. & 2008 Cancer Research UK Offspring N RR (95% CI) 27 1.12 (0.76 – 1.63) 100 1.28 (1.05 – 1.57) 56 1.22 (0.93 – 1.58) 51 1.12 (0.85 – 1.48) 108 1.13 (0.93 – 1.37) 151 1.04 (0.88 – 1.22) 22 0.81 (0.53 – 1.23) 51 1.45 (1.10 – 1.91) 28 0.88 (0.60 – 1.27) 233 1.17 (1.03 – 1.34) 55 1.22 (0.93 – 1.59) 72 1.10 (0.87 – 1.39) 36 1.30 (0.94 – 1.81) 51 0.94 (0.71 – 1.24) 37 1.06 (0.77 – 1.47) 18 0.88 (0.55 – 1.40) 10 1.16 (0.62 – 2.15) 39 1.04 (0.76 – 1.43) 21 0.93 (0.61 – 1.44) 53 1.34 (1.02 – 1.76) 1446 1.50 (1.39 – 1.61) Sibling N RR (95% CI) 5 0.79 (0.33 – 1.89) 9 1.35 (0.70 – 2.59) 6 1.12 (0.50 – 2.49) 13 2.18 (1.27 – 3.77) 31 1.35 (0.95 – 1.92) 80 1.05 (0.84 – 1.31) 13 1.46 (0.85 – 2.51) 20 1.63 (1.05 – 2.54) 11 0.93 (0.52 – 1.69) 59 1.45 (1.12 – 1.88) 4 3.25 (1.22 – 8.68) 12 0.87 (0.49 – 1.53) 28 1.34 (0.93 – 1.95) 13 1.67 (0.97 – 2.87) 21 1.19 (0.77 – 1.83) 13 1.36 (0.79 – 2.34) 3 1.26 (0.41 – 3.91) 10 2.63 (1.42 – 4.90) 9 0.95 (0.49 – 1.83) 451 1.44 (1.30 – 1.59) Familial risk of colorectal adenoma E Hiripi et al CI ¼ 1.05 – 1.57), endometrial (RR ¼ 1.45; 95% CI ¼ 1.10 – 1.91) and prostate (RR ¼ 1.17; 95% CI ¼ 1.03 – 1.34) cancers. Colorectal adenoma showed increases among those whose siblings had multiple myeloma (RR ¼ 2.63; 95% CI ¼ 1.42 – 4.90), endometrial (RR ¼ 1.63; 95% CI ¼ 1.05 – 2.54) and pancreatic cancer (RR ¼ 2.18; 95% CI ¼ 1.27 – 3.77). The risk was also increased when parents or siblings had cancer at any site (RR ¼ 1.50; 95% CI ¼ 1.39 – 1.61, RR ¼ 1.44; 95% CI ¼ 1.30 – 1.59, respectively). The risk of site-specific colorectal adenoma was examined according to parental and sibling history of cancer at specific sites (result not shown). Sigmoid adenomas were associated with parental history of liver cancer (RR ¼ 1.69; 95% CI ¼ 1.09 – 2.64; N ¼ 20), and with a sibling history of melanoma (RR ¼ 2.06; 95% CI ¼ 1.13 – 3.73; N ¼ 11). A sibling history of cervical or nervous system cancer was associated with an increased risk of rectal adenoma (RR ¼ 2.44; 95% CI ¼ 1.31 – 4.54; N ¼ 10, RR ¼ 1.72; 95% CI ¼ 1.02 – 2.92; N ¼ 14, respectively). Rectal adenoma was also related to parental history of melanoma (RR ¼ 1.63; 95% CI ¼ 1.06 – 2.51 N ¼ 21). DISCUSSION The present study indicates that individuals with first-degree relatives with colorectal adenoma have an approximately five times higher probability of this neoplasm than those without a family history; the risk being particularly high among relatives of those with multiple adenomas. As in previous studies risk was increased among offspring and siblings of CRC patients (Bonelli et al, 1988; Tung and Wu, 2000; Lindgren et al, 2002). To our knowledge, there are no studies of colorectal adenoma in relation to a family history of extracolonic cancers. The present data suggest an involvement of colorectal adenoma in HNPCC and associations with the commonest HNPCC cancer sites – endome- trium, stomach, pancreas and nervous system – were identified (Lynch and de la Chapelle, 2003). We also found colorectal adenoma associated with some extra- colorectal cancers unrelated to CRC. There was a higher risk of colorectal adenoma for the offspring and siblings of patients with prostate cancer. The siblings of patients with multiple myeloma and the offspring of patients with leukaemia were at an increased risk of colorectal adenoma. Increased risks of CRC are reported among first- degree relatives of patients with leukaemia (Andrieu et al, 2004; Hemminki and Chen, 2004), myeloma (Hemminki and Li, 2001), and prostate cancer (Slattery and Kerber, 1994). We also found that the offspring of those with adult acute lymphoblastic leukaemia were at a higher risk of colorectal adenoma. Rectal adenoma risk was increased among siblings of women with cervical cancer. An increased risk of rectal cancer before the age of 50 years has been reported among the offspring of women with cervical cancer after the age of 50 years (Hemminki and Chen, 2004), but the risk was not increased among siblings of such women. Moreover, the risk of rectal cancer as a second tumour seems to be increased after a first cervical cancer (Hemminki et al, 2001a). The familial association of rectal adenoma with melanoma should be investigated using independent data. Our study had the advantage of information on the anatomical location of the colonic tumours, but our analyses were limited by small numbers, although this problem can be addressed when the Database in further updated. During our study, Sweden had no population-based screening programmes for CRC (Hakama et al, 2005). Some individuals in our study may have undergone colonoscopic screening because of a family history of CRC, as the risks reported in Tables 2 and 3 could be overestimated. Another limitation is that only precancerous lesions and gastro- intestinal polyps with suspected malignancy are compulsorily reported to the Cancer Registry and some adenomas might be already precancerous. A shortcoming is the lack of data on tobacco smoking, alcohol consumption, or diet. British Journal of Cancer (2008) 98(5), 997 – 1000 999 y g o l o i e d i p E