Increased risk of ovarian cancer in integrin beta3 Leu33Pro homozygotes.
ABSTRACT We previously demonstrated that integrin beta(3) Leu33Pro homozygotes have an increased risk of cancer, possibly most pronounced for ovarian cancer. We now test the latter hypothesis in case-control and prospective studies. We genotyped 463 Danish women with ovarian cancer, and 4291 women from the Danish general population. Calculation of odds ratios by conditional logistic regression was performed in the case-control study (n = 463 + 3543), and of ovarian cancer incidence, log-rank statistics and hazard ratios by Cox regression in the prospective study (n = 4291) with 9.5-year follow-up. In the case-control study matched for age and marital status, the odds ratio for ovarian cancer in homozygotes versus non-carriers was 1.6 (95% confidence interval: 1.0-2.6). In the prospective study with 28 incident ovarian cancers, non-carriers and homozygotes had incidences of 7 (4-11) and 30 (10-92) per 10 000 person-years (log-rank P = 0.02). The age-adjusted hazard ratio for ovarian cancer in homozygotes versus non-carriers was 3.9 (1.1-13). Risk of ovarian cancer did not differ between heterozygotes and non-carriers in either study. Integrin beta(3) Leu33Pro homozygotes have an increased risk of ovarian cancer.