An inverse association between ovarian cysts and breast cancer in the breast cancer family registry.

Ovarian cysts of several types are common in women of reproductive age. Their etiology is not well understood but is likely related to perturbations in the hypothalamic-pituitary-gonadal axis. The relationship of ovarian cysts to breast cancer risk is not known, although a negative association with polycystic ovarian syndrome has been reported. Incident, invasive female breast cancer cases, population-based controls and unaffected sisters of cases were studied from 3 countries participating in the Breast Cancer Family Registry: Melbourne and Sydney, Australia; the San Francisco Bay Area, USA; and Ontario, Canada. Using the same questionnaire, information was collected on self-reported history of ovarian cysts and other risk factors. Analyses were based on 3,049 cases, 2,344 population controls and 1,934 sister controls from all sites combined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using both unconditional and conditional logistic regression using an offset term to account for sampling fractions at 2 of the sites. A significantly reduced risk of breast cancer was observed for women reporting a history of ovarian cysts (OR = 0.70, 95% CI 0.59-0.82, among all cases and all controls). This risk estimate was similar regardless of control group used, within all 3 sites and in both premenopausal and postmenopausal women (ORs ranging from 0.68-0.75, all 95% CI excluded 1.00). A self-reported history of ovarian cysts was strongly and consistently associated with a reduced risk of breast cancer. Further study of ovarian cysts may increase our understanding of hormonal and other mechanisms of breast cancer etiology.

Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry.

There are several genes that code for enzymes, including various forms of superoxide dismutase and glutathione peroxidase, that protect the cell against oxidative damage that, in turn, can lead to carcinogenesis. There are a few common genetic polymorphisms in these genes that lead to altered proteins. Three that have been identified are SOD2 Val-9Ala, GPX1 Pro198Leu, and the GPX1 GCG repeat (three alleles with four, five, or six repeats). The SOD2 variant has been associated with increased breast cancer risk in two studies. The GPX1 variants have not been studied with respect to breast cancer, but Pro198Leu has been associated with lung cancer. We conducted a case-control study of these three polymorphisms in incident, invasive breast cancer in Caucasian women under 55. There were 399 cases and 372 controls genotyped, of whom 488 were premenopausal, 208 postmenopausal, and 75 of unknown menopausal status. We were unable to replicate the previously observed association with SOD2 Val-9Ala and also found no association between breast cancer and GPX1 Pro198Leu. However, the allele of GPX1 containing four GCG repeats was significantly associated with breast cancer risk in premenopausal women (odds ratio, 1.55; 95% confidence interval, 1.04-2.30 for carriers versus noncarriers). There is a significant trend of increasing risk with increasing number of alleles with four GCG repeats (P = 0.03). This variant has not previously been reported to be associated with breast cancer.