Malignancies associated with gynecological cancer : epidemiological and etiological aspects

Sammanfattning: The aims of this thesis were to analyze the incidence and risk of second primary malignancies (SPM) in a Swedish cohort of gynecological cancer patients, to explore suggested risk factors associated with second primary malignancies in ovarian cancer patients, and to evaluate the risk of ovarian cancer in a cohort of breast cancer patients in relation to family history of breast or ovarian cancer. Incidence of second primary malignancies in 15,200 gynecologicaI cancer patients were investigated in a register-based study and compared to age- and calendar-specific incidence for women in the general population. Increased risk of leukemia was found after ovarian and endometrial cancer. Additional sites of excess risk in ovarian cancer patients were breast, endometrial, colon, rectum, and bladder, while women with endometrial cancer were documented having an increased risk of cancer of the colon, ovaries, vulva, and bladder. Cervical cancer patients were found with increased risk of cancer of colon, rectum, lung, vulva, kidney, and bladder (Paper I). Validity of register data was investigated by comparisons with hospital records for 347 women registered with ovarian cancer and one or more second primary malignancy. Errors in cancer registrations were revealed concerning the first as well as the second primary cancer, although previously risk estimates remained increased when corrected for registration errors (H). In a multi-center case-control study, platinum-based chemotherapy was shown to be highly associated with an increased risk of leukemia (HI). The risk of second primary breast cancer in women with ovarian cancer was associated with heredity, nulliparity, and late menopause. Furthermore, 43 % of the breast cancer cases were diagnosed without symptoms of the disease in line of routine follow-up, indicating clinical surveillance to be important when reflecting the incidence of SPM (IV). In order to further investigate family history as a risk factor, the risk of ovarian cancer in breast cancer patients was analyzed using data from the Swedish Generation Register. Breast cancer patients with a family history of breast or notably ovarian cancer were found to be at high risk of subsequent ovarian cancer (V). The results confirm that women with gynecological cancer have an increased risk of second primary malignancies at certain sites, knowledge that should be considered in clinical follow-up. In ovarian cancer patients, a part of the excess risk of subsequent malignancies could be referred to register errors and intense clinical surveillance. Regarding the appearance of ovarian cancer as a second primary malignancy in breast cancer patients, the risk was found to be high in young women with a family history of breast or ovarian cancer, implementing the need of intense clinical surveillance in high-risk groups, even considering prophylactic oophorectomy in selected cases.