Familial clustering of ovarian and endometrial cancers
Introduction
Invasive ovarian cancer has declined in incidence in Sweden over the past two decades and with an incidence of less than 20/100 000, it ranks sixth among all female cancers [1]. The incidence of endometrial cancer has been increasing and it ranks third among female cancers, although the incidence is not much higher than that of ovarian cancer. Both of these cancers are mechanistically linked to reproductive hormones, and the number of ovulatory cycles is a risk factor for both 2, 3, 4. Most ovarian tumours are adenocarcinomas derived from the surface epithelium [5]. They present in many morphological forms such as cystadenocarcinomas, with serous or mucinous secretions, or endometrioid tumours, with endometrial-like tubular gland structures. Endometrial neoplasms are also adenocarcinomas, which may retain a well-defined glandular structure, referred to as endometrioid carcinoma [5].
Ovarian cancer occurs in families with BRCA1/2 mutations and in hereditary non-polyposis colorectal cancer patients (HNPCC) 6, 7, 8, 9. In the BRCA1/2 families, the tumours display small histopathological distinctions, being mainly non-mucinous 7, 8, 10, 11. Even in HNPCC families, the histopathology resembles that of sporadic tumours, with a small excess of endometrioid tumours [12]. Endometrial cancer is the most common extracolonic manifestation in HNPCC families and mismatch repair defects are also common in sporadic tumours 13, 14, 15. The PTEN gene is also commonly affected in sporadic endometrial tumours 15, 16, 17. In addition to the known cancer syndromes, both ovarian and endometrial cancers show familial clustering. The reported familial risk among first-degree relatives has been reported to range between 2.0 and 3.0 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29. Many of these studies have also analysed the association of ovarian and endometrial cancers with other cancers in families 18, 21, 22, 24, 26, 27, 28, 29. Some studies have noted an association of these cancers to breast cancer, and a few other sites have emerged in individual studies. An association between ovarian and endometrial cancer has been observed in only three studies, all of which analysed young populations of women 21, 26, 29. Most family studies, particularly on ovarian cancer, have been based on interviews of cases and controls about cancer in their relatives. The accuracy of reporting intra-abdominal cancers diagnosed a long time ago may have biased the risk estimates in the interview studies.
We examine here, the association of ovarian cancer with other cancers in family members, using the nationwide Swedish Family-Cancer Database [30], which has been updated in 2000 to include over 10 million individuals and over 1 million registered tumours retrieved from the Swedish Cancer Registry from 1961 to 1998. Data on morphological classification, based on the International Classification of Diseases (ICD)-O-2 coding system, are available since 1993. The Database is unique in its size and its unbiased structure, because the data on family relationships and cancers were obtained from registered sources of practically complete coverage.
Section snippets
Patients and methods
The Swedish Family-Cancer Database was initially created in the mid-1990s by linking an administrative family register on all Swedish families to the Swedish Cancer Registry, including data from 1961 to 1998 30, 31, 32. For each child, there are data on both parents at the time of birth. Each person has been assigned a unique technical identification number (which is different from the national identification number, ‘personal number’), allowing, for example, the construction of families
Results
The Family-Cancer Database included data from 1961 to 1998 from the Swedish Cancer Registry, on 15 040 mothers and 4135 daughters with ovarian cancer, respectively. We first considered all ovarian cancers without histological specification. Familial risks for ovarian cancer in daughters are shown in Table 1 by cancer in mothers, and vice versa. The data were adjusted for age, period, parity, age at first birth, socio-economic index (SEI) and region. Only sites with at least 20 cases in any
Discussion
The present study is the largest on familial ovarian cancer published to date and the number of concordant ovarian cancers in mother–daughter pairs is almost as large as that of four previous cohort studies combined 20, 22, 24, 28. We have used the same population recently in an analysis of concordant ovarian cancer, and we will refer to detailed data in this source [34]. To summarise for concordant ovarian cancer, the most common morphology, seropapillary cystadenocarcinoma, showed the highest
Acknowledgments
The Family-Cancer Database was created by linking registers maintained at Statistics Sweden and the Swedish Cancer Registry.
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Two sisters with Mayer-Rokitansky-Küster-Hauser syndrome and serous adenocarcinoma of the ovary
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2013, Tzu Chi Medical JournalCitation Excerpt :Women who have never gone through pregnancy seem to have an increased risk of EOC [10]. A decreased risk of EOC has been associated with women who have had a full-term pregnancy [10–12]. A higher ovarian cancer risk is also seen in women who are infertile [13,14] and in women who have endometriosis or polycystic ovarian syndrome.
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