Report in English with a Dutch summary (KCE reports 45A)

40 Screening for Colorectal Cancer KCE reports vol.45
A Swedish study focused on secondary cancers in 68.104 cases of CRC from
the Swedish Family-Cancer Database 142. In 1.113 patients a secondary CRC was
diagnosed; 25 of them had a family history of CRC. Cases of secondary CRC
with a family history were diagnosed up to 10 years before sporadic cases. The
RR of all secondary CRCs was 2,21 compared with the first CRC. Familial
secondary CRCs had a 2-fold risk compared with the sporadic forms. Age of
onset was the most important covariate of secondary CRCs; the relative risk at
ages 15 - 39 years was 27 compared with the first CRC. Familial CRC was
associated with a high risk of small-intestinal, endometrial, and gastric cancers
apart from CRC, all typical of HNPCC. Among familial cases, 36% of secondary
CRCs and 100% of endometrial cancers came from families that fulfilled the
Bethesda criteria for HNPCC 145, 58. Only 12 families conformed to the
Amsterdam criteria; in family members, the risk of secondary CRC was 127-fold
and that of endometrial cancer 257-fold. Other sites that were in excess among
all secondary cancers were many cancers linked to HNPCC and, additionally,
breast, prostate, thyroid and other endocrine, skin, and genital cancers. The
authors concluded that the high risk of secondary cancer after early-onset CRC
calls for evaluation of family history and clinical surveillance.
Adenoma prevalence and cancer risk in familial non-polyposis colorectal cancer
was further studied in Sweden 123. Over a period of 10 years, 304 subjects at risk
were included in ongoing surveillance with regular colonoscopies. To compile
the medical findings and experience generated during this period, a
retrospective cross sectional study was performed. Subjects were classified into
three family groups: families with HNPCC (Lynch syndrome), families with
hereditary colorectal cancer (HCC, non-Lynch syndrome) and a third group of
families with only empirical risk estimates based on a family history of two close
relatives (TCR) with CRC. The risk population was studied with regard to age
at onset, prevalence, number, cancer risk, size, dysplasia, and distribution of
adenomas. A comparison was made within the family groups and with a
reference group representing the general population. In total, 195 adenomas
and six cancers were detected among 85 individuals. The relative risk of having
an adenoma in the whole risk population compared with the general population
was 2,6. Subjects from TCR families had most adenomas and HNPCC subjects
had the least. A shift from proximal adenomas to distal carcinomas in families
with HCC and TCR suggested a higher cancer risk in distal adenomas in these
syndromes. HNPCC families showed a younger age at onset and adenomas with
a higher degree of dysplasia. In HNPCC there was a similar localisation of
adenomas and carcinomas, suggesting a high risk of cancer in all adenomas. The
study showed that there was clear overrepresentation of adenomas in all three
family types compared with the reference population. In HNPCC there was
earlier onset of adenomas and faster progression to cancer. Families with HCC,
and even more so TCR subjects, had a later onset and lower risk of cancer
from proximal adenomas. Based on these results, surveillance protocols in
Sweden have been revised.
A retrospective review of the French Calvados Cancer Registry 1993 - 1998,
published in 2004 143, showed that colon cancer had a familial or genetic
component but not rectal cancer: RR 1,47 (95% CI: 1,16-1,96; p value 0,004) vs.
RR 0,98 (95% CI: 0,67-1,40). The familial/genetic component appeared stronger
for proximal colon cancer than for distal colon cancer, but only among women:
RR 2,24 (95% CI: 1,35-3,50) vs. RR 1,45 (95% CI: 0,83-2,36).
Another French population study 140 aimed to estimate the lifetime risk (0 - 74
y) of CRC in the general population (males versus females) and in first degree
relatives of patients with sporadic colorectal cancer or adenoma. The lifetime