Calcitonin gene polymorphism CALCA-624 (T/C) and ovarian cancer

In a previous analysis, we reported an inverse association of dietary calcium intake with the risk of ovarian cancer (Goodman et al. 2002. Am J Epidemiol 156:148-57). The CALCA gene codes for calcitonin, an important regulator of bone calcium metabolism. Data from a population-based case-control study conducted in Hawaii were used to examine the hypothesis that a T --> C transition 624 base pairs upstream (-624) of the translation initiation codon of the CALCA gene influences the risk of ovarian malignancy. A structured interview was conducted for 182 histologically confirmed ovarian cancer cases and 219 controls. Blood specimens were collected from the subjects at their homes. A significant negative trend (P for trend: 0.02) in the odds ratios (ORs) was found with increasing intake of calcium. Women with any CALCA C allele were at nonsignificantly higher risk of ovarian cancer (OR: 1.5, 95% CI: 0.9-2.3) compared to women with the TT genotype and the risk increased with the number of C alleles (P for trend: 0.05). When further analyzed within ethnic subgroups, a significant positive association was found among Japanese for CALCA CT (OR: 2.3, 95% CI: 1.0-5.3) and CALCA CC (OR: 7.2, 95% CI: 1.1-46.0) compared with Japanese women who were homozygous for the T allele. The trend in risk associated with the C allele was most significant among women who had used oral contraceptives (P for trend: 0.05), had been pregnant (P for trend: 0.04), and had nonmucinous histological types of ovarian cancer (P for trend: 0.02). However, the association of ovarian cancer risk with the CALCA genotype was not significantly modified by any of the dietary, nondietary, or clinical variables included in this study. These preliminary data suggest a strong positive association of the CALCA C allele with the risk of ovarian cancer among some subgroups.