Family History of Reproductive Cancers and Ovarian Cancer Risk: An Italian Case-Control Study

Summary Cancer incidence was studied among 3072 first-degree relatives of 559 unselected ovarian cancer patients. Among cohort members there were 306 cancer cases. The overall cancer incidence was not increased: the standardised incidence ratio (SIR) in males was 0.9 (95% confidence interval 0.8-1.1) and in females 1.0 (0.8 -1.1). The female relatives had a significantly increased risk for ovarian cancer (SIR 2.8, 1.8-4.2). The excess was attributable to sisters only (SIR 3.7, 2.3 -5.7). The relative risk for ovarian cancer among sisters decreased both by increasing age of the sister and by increasing age at diagnosis of the index patient: the SIRs were 7.3 (1.5-21.4), 4.5 (1.6-9.8) and 3.1 (1.7-5.4) for sisters of index patients diagnosed in age <45, 45 -54 and 55 -75 years respectively. The age dependency of the risk supports the role of genetic factors in familial ovarian cancer. Although the risk of ovarian cancer among sisters from families with breast cancer (SIR 9.2, 3.7-19.0) was significantly higher than among sisters from families with no breast cancer patients (SIR 2.9, 1.6-4.8, rate ratio 3.1, P < 0.05), the excess was not solely attributable to coaggregation of breast and ovarian cancer. Among the 27 families with two or more ovarian cancers, only sisters were affected in 24 families, which might implicate recessive inheritance or shared environmental factors influencing ovarian cancer risk in sisters.

Section: Resultsmentioning

confidence: 97%

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confidence: 99%

Cancer incidence in the first-degree relatives of ovarian cancer patients

Auranen

Pukkala²,

Mäkinen³

et al. 1996

“…For instance, the risk of metachronous second primary breast cancer was elevated by 70% on a population (publick health) level, but the real excess risk for epidemiological and etiological inference is probably double, since most women have only one breast at risk following surgery for breast cancer (Peto, 1987). The excess breast cancer incidence following primary ovarian cancer may be due to genetic susceptibility (Parazzini et al, 1992), besides common aetiological correlates (Franceschi, 1989). The association between multiple colorectal cancers, kidney and bladder cancer and melanoma and non-melanomatous skin cancers may be due to the action of common risk factor exposure, but also to the increased surveillance following a cancer diagnosis, which may be of particular relevance for skin neoplasms and explain the association of non-melanomatous skin cancer with other neoplasms (e.g., leukaemias).…”

Section: Discussionmentioning

confidence: 99%

Multiple primary cancers in the Vaud Cancer Registry, Switzerland, 1974-89

Levi

Randimbison²,

Te³

et al. 1993

Sunnnary Data collected by the Cancer Registry of the Swiss Canton of Vaud (whose population in 1980 was about 530,000 inhabitants) were used to estimate the incidence of second metachronous primary cancers following any specific neoplasm. Among 34, 615 cases of incident neoplasms registered between 1974 and 1989 and followed through integrated active follow-up to the end of 1989, for a total of 118,241 person-years at risk, there were 2,185 second primaries (1,280 males, 905 females). For both sexes, the standardised incidence ratios (SIR) were significantly elevated by about 20%. Overall significantly elevated ratios were registered for cancers of the oral cavity and pharynx (SIR = 1.6 for males, 2.0 for females), oesophagus in males (SIR = 1.5), lung in males (SIR = 1.4), skin melanoma (SIR = 1.7 for males, 1.5 for females), non-melanomatous skin cancers (SIR = 1.6 for males, 1.5 for females), female breast (SIR = 1.3), kidney (SIR = 1.5 for males, 1.9 for females), and thyroid in males (SIR = 2.4). When specific first cancer sites were considered, the SIR following a cancer of the oral cavity and pharynx was around 3 in both sexes, mainly on account of a substantial excess of second primaries of the oral cavity, oesophagus, larynx and lung. The overall SIR following laryngeal cancer was 3.0, and significant excesses were observed for oral cavity and pharynx, oesophagus and lung. After lung cancer, the overall SIR was 1.7 for males and 2.6 for females, and significantly elevated SIRs were observed for oral cavity, lung and oesophagus. Following non-melanomatous skin cancers, elevated SIRs were observed in both sexes for skin melanoma and non-melanomas. The incidence of any cancer after breast cancer was significantly elevated (SIR = 1.2), mainly on account of an elevated risk of subsequent breast cancer (SIR = 1.7). With reference to cervical cancer, there was a significant excess for any subsequent primary (SIR = 1.6), and for lung cancer (SIR = 7.8). Significantly elevated SIRs were observed for kidney following bladder cancer, and for bladder after kidney cancer. In both sexes, the incidence of cancers of any site was elevated following leukaemias (SIR = 1.7 for males, 2.5 for females), and a significant excess was registered for lung in males and non-melanomatous skin cancers in both sexes. Some of the associations observed can be related to common risk factor exposure, such as tobacco (and alcohol) for multiple primaries of the upper digestive and respiratory tract, or tobacco for the excess of lung cancer following bladder and probably cervical cancer. However, the overall excess risk of a second primary cancer is relatively limited, and at least in part attributable to increased surveillance.

“…Evidence for this comes from two sources: epidemiological case-control studies, in which the first-degree relatives of ovarian cancer patients have been observed to have a two-to fivefold increased risk for ovarian cancer (Hartge et al, 1989;Schildkraut et al, 1989;Parazzini et al, 1992;Houlston et al, 1993;Goldgar et al, 1994;Hartge et al, 1994;Kerber and Slattery, 1995); and from family studies, which have identified families prone to ovarian cancer or, more commonly, to ovarian and breast cancer (Liber, 1950;Lewis and Clare Davidson, 1969;Li et al, 1970;Lynch et al, 1974;Fraumeni et al, 1975;Thor et al, 1976).…”

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confidence: 99%

“…This type of familial ovarian cancer contributes to the majority of the risk increase observed in the first-degree relatives (Schildkraut and Thompson, 1988;Parazzini et al, 1992). To what extent familial ovarian cancer can be explained by mutations in the BRCAJ and BRCA2 genes or mutations in the other known dominantly inherited cancer-predisposing genes, most importantly those involved in the hereditary non-polyposis colorectal cancer (HNPCC; Aaltonen et al, 1994), is unresolved.…”

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confidence: 99%

Segregation analysis of epithelial ovarian cancer in Finland

Auranen

Iselius²

1998

Summary Epithelial ovarian cancer is known to aggregate in families. The dominantly inherited ovarian cancer predisposing genes, BRCA 1, BRCA2 and genes involved in the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, have recently been identified. However, in the majority of families with more than one case of ovarian cancer, dominant inheritance cannot be recognized. We investigated familial clustering of epithelial ovarian cancer in a population-based sample of 663 Finnish ovarian cancer patients. A segregation analysis with the POINTER software was conducted on the 937 nuclear families from these 663 pedigrees. The major gene model was favoured, and the sporadic and multifactorial models were strongly rejected. In the studied population, the best fitting model was a recessive mode of inheritance, and 8% of ovarian cancer patients were estimated to be homozygous for the deleterious genotype. This evidence for recessively inherited ovarian cancer predisposition should be interpreted cautiously, as the analysis is subject to certain errors, which are discussed in the article. Results of this analysis, however, strongly emphasize the role of genetic factors in all familial aggregation of epithelial ovarian cancer.