Familial Risks in in Situ Cancers from the Family-Cancer

The Swedish Family-Cancer Database was used to analyze relationships between parents and offspring with in situ cancers and between in situ cancers in one generation and invasive cancer in the other generation. A total of 130,000 in situ cancers and close to 400,000 invasive cancers were included from 1959 to 1994. The data on family relationships and cancers came from registered sources and should be free from bias. The offsprings’ familial relative risks (FRRs) were calculated for concordant and discordant parental cancer sites. The most common male in situ site was skin (both melanoma and precancerous epithelial lesion), whereas cervix, breast, and skin were conunon female sites. Increased FRRs were observed for concordant sites: colon, breast, cervix, skin (melanoma), and, in males, precancerous epithelial lesions. The findings were consistent when in situ cancer-in situ cancer and in situ cancer-invasive cancer relationships were explored. FRRs were higher for in situ colon cancer and melanoma than the respective estimates in invasive cancers, and for the remaining sites, they were equal or somewhat lower. At discordant sites, increased FRRs of in situ cancers were observed for female breast and melanoma and, at many sites, implicated in tobacco and human papilloma virus carcinogenesis, together with cervix. Family histories of in situ cancers deserve clinical attention. Introduction Noninvasive (in situ) cancers are becoming more common at many sites due to intensified screening programs and clinical diagnostic methods. Noninvasive cancers have a tendency to progress to invasive cancer; therefore, treatment of in situ cancers is thought to prevent metastasis of the disease. Etiological data on in situ cancers are scanty, but the assumption is that the risk factors are similar to those of invasive cancers. For breast cancer, this has been addressed in analytical epidemiological studies. Established risk factors of breast cancer were found to increase the risk of breast cancer in situ, but probably Received 4/20/98; revised 6/23/98; accepted 7/14/98. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. i The work was supported by The Swedish Council for Planning and Coordination of Research, The Stockholm County Council, The Cancer Fund, and The King Gustaf V Jubileefund. 2 To whom requests for reprints should be addressed, at Center for Nutrition and Toxicology Novum, 141 57 Huddinge, Sweden. Phone: 46-8-6089243; Fax: 46-8-6081501; E-mail: [email protected]. more for the ductal than for the lobular form (1-3). In all these studies, family history was found to a be risk factor: risk of developing ductal breast cancer in situ was -2.5-fold in women whose first-degree relatives had a breast cancer (2, 3). In lobular cancer in situ, the familial risk was confined to those diagnosed before the age of 50 years (1). The Swedish Cancer Registry has recorded cancers since 1958, but for in situ cancers, reporting improved around 1970. All these cancers are included in the nationwide Swedish Family-Cancer Database, by far the largest database ever used for the study of familial cancer. It offers unique possibilities for reliable estimation of familial risks because all of the data on family relationships and cancers were obtained from registered sources of complete coverage. This database has previously been used to study familial relationships in invasive cancers (4_9)#{149}3Here, we investigated familial relationships in noninvasive and invasive cancers at single sites and across sites. FRRs4 were calculated for offspring with in situ cancer when their parents had similar or different cancers. Subjects and Methods The Swedish Family-Cancer Database includes all persons born in Sweden in 1941 with their biological parents, totaling over 6 million individuals (4-7). Since the previous studies, the database has been enhanced with information on those who have died since 1960, making it practically complete for studies on adult cancer (8). Cancers, including in situ cancers, were retrieved from the nationwide Swedish Cancer Registry from 1958 to 1994 (10). A four-digit diagnostic code according to the 7th Revision of the International Classification of Diseases was used. Offspring were diagnosed for their first primary cancer in 1958-1994 at ages 15-53 years. Those diagnosed for their first primary before the age of 15 years were excluded from the study population to distinguish the adult and childhood forms of cancer. The following 7th Revision of the International Classification of Diseases codes were pooled: “lymphoma” codes 200 (non-Hodgkin’s lymphoma), 201 (Hodgkin’s disease), and 202 (reticulosis); and “leukemia” codes 204-207 (leukemias), 208 (polycytemia vera), and 209 (myelofibrosis). Basal cell carcinoma of the skin is not registered in the Cancer Registry. The most common in situ diagnoses were precancerous lesion of lip, mouth, and larynx; colonic/rectal polyp with precancerous change; carcinoma in situ of the uterine cervix (squamous cell type); precancerous change of breast and adenoma phyllodes; malignant melanoma in situ of the skin; and precancerous epithelial lesions of the skin. in situ cancers were selected for analysis if there were at least 70 sex-specific cases in the offspring, limiting the number of sites considered to 7. These sites were also of primary interest in the in situ-invasive cancer comparisons. However, 3 K. Hemminki and P. Vaiuinen. Familial risks in common cancer analyzed from the nation-wide Family-Cancer Database, manuscript in preparation. 4 The abbreviations used are: FRR, familial relative risk; Cl, confidence interval. on October 20, 2017. © 1998 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from 866 FamIlial Risk of in Situ Cancer Table I Number of cases fcr 10 most common invasive cancer and in situ ancer sites in the Family-Cancer Database Invasive cancer in situ cancer . No.of Site . Site No.of cases cases Fathers Prostate Lung Urinary organ Colon Stomach Rectum