© 2005 Oxford University Press
IN THIS ISSUE
Randomized Trial of Systematic LymphadenectomyMost cases of ovarian cancer are diagnosed at advanced stages, and survival rates are low. A key component of treatment is surgery to remove as much tumor as possible, but whether surgery should include systematic removal of retroperitoneal lymph nodes has been less clear. In this issue, Benedetti Panici et al. (p. 560) report the results of a randomized trial of 427 women with advanced ovarian cancer treated with cytoreductive surgery plus systematic aortic and pelvic lymphadenectomy or with cytoreductive surgery only. After a median follow-up of more than 5.5 years, women in the systematic lymphadenectomy arm had better progression-free survival than women in the control arm. However, overall survival was the same in both arms. Women who had systematic lymphadenectomy had more intraoperative complications and greater perioperative and late morbidity than women who had cytoreductive surgery only.
In an editorial, Chambers (p. 548) points out that the authors do not provide details about the types and severity of the late morbidities or address the survival impact of the resection of positive lymph nodes with systematic lymphadenectomy. Nevertheless, she notes, the trial shows the high morbidity and lack of survival advantage with systematic lymphadenectomy, which should discourage its routine use in the management of advanced ovarian cancer.
Genetic Polymorphisms and Lung Cancer Risk
Hung et al. (p. 567) examined associations between each of four polymorphisms of base excision repair genes (OGG1 Ser326Cys, XRCC1 Arg194Trp, XRCC1 Arg280His, and XRCC1 Arg399Gln) and lung cancer risk among 2188 lung cancer patients and 2198 control subjects without lung cancer and estimated the false-positive reporting probabilities for their results. Overall, neither the OGG1 genotype nor the XRCC1 polymorphisms were associated with lung cancer risk. However, subjects who carried the OGG1 Cys/Cys genotype had an increased risk of adeno-carcinoma compared with subjects who carried the Ser/Ser genotype, and the XRCC1 Arg194Trp and Arg280His polymorphisms were each associated with a reduced risk of lung cancer among heavy smokers. From the results of a false-positive report probability analysis, the authors conclude that the subgroup results for the XRCC1 Arg280His polymorphism is likely a false-positive result and the findings on OGG1 Ser326Cys and XRCC1 Arg194Trp are likely true associations.
In an editorial, Matullo et al. (p. 550) write that estimating false-positive reporting probabilities of associations among genetic variants, environmental exposures, and disease can be problematic because the best way to calculate prior probability remains unclear. The authors describe how well-done meta-analyses or pooled analyses might be a useful way to obtain estimates of prior probabilities.
HPV and Reactivation in HIV-Positive Women
To investigate how the combination of plasma HIV RNA level and CD4+ T-cell count in HIV-positive women is associated with the natural history of human papillomavirus (HPV) infection, Strickler et al. (p. 577) conducted semiannual assessments of HIV-positive and -negative women for cervicovaginal HPV. They observed a strong statistical interaction between the associations of CD4+ T-cell count and of plasma HIV RNA level with both prevalent and incident detection of HPV and a more modest association of HIV coinfection with persistence of HPV. They conclude that the combination of plasma HIV RNA level and CD4+ T-cell count in HIV-positive women appears to have a strong interactive association with incident detection of HPV, some of which may reflect HPV reactivation. The more modest association between HIV coinfection and HPV persistence may help explain why cervical cancer rates have not reached more epidemic proportions in HIV-positive women.
Immune System Development and Non-Hodgkin Lymphoma
Immune deficiency is a strong risk factor for Non-Hodgkin lymphoma (NHL), which arises from cells of the immune system. Whether atopy, another form of immune system dysregulation, is associated with NHL has been less clear. To examine this association, Grulich et al. (p. 587) carried out a population-based case–control study of NHL patients without immune deficiency. Late birth order and childhood crowding are inversely associated with atopy, possibly because these conditions confer early-life exposure to infectious agents, which has immunologic consequences not seen in only children or those of early birth order. Therefore, the authors assessed birth order and history of childhood crowding as well as history of atopic conditions (such as hay fever and asthma). The risk of NHL was inversely related to birth order, with only and first-born children at lowest risk. A history of atopic conditions was also associated with a reduced risk of NHL.
Sex Hormones and Postmenopausal Breast Cancer
To determine if postmenopausal hormone (PMH) use alters sex hormone levels and breast cancer risk, Tworoger et al. (p. 595) conducted a prospective nested case–control study within the Nurses' Health Study cohort from 1989–1990 through May 31, 2000. The authors observed that PMH users had higher levels of estradiol, free estradiol, sex hormone-binding globulin, and testosterone and lower levels of free testosterone than nonusers. Modest associations were found between free estradiol, free testosterone, and sex hormone-binding globulin levels and breast cancer risk in PMH users overall, and estradiol and free estradiol were positively associated with risk among women older than 60 years and those with a body mass index of less than 25 kg/m2. The authors conclude that plasma sex hormone concentrations are associated with breast cancer risk among PMH users.
Male Breast Cancer Incidence Among Atomic Bomb Survivors
To learn more about the role of ionizing radiation in the development of male breast cancer, Ron et al. (p. 603) evaluated the incidence of the disease in 45 880 male members of the Life Span Study cohort of Japanese atomic bomb survivors. Through tumor registries, the authors identified nine male breast cancers diagnosed between Jan. 1, 1958, and Dec. 31, 1998, among men exposed to atomic bomb radiation compared with three cases diagnosed among men not exposed to atomic radiation. They found a dose-response relationship between male breast cancer and exposure to ionizing radiation. The authors conclude that their results add to the limited information that shows an association between radiation exposure and an increased risk of male breast cancer.
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