Table 2. Association Between Genetically Proxied Inhibition of 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) Reductase, Niemann-Pick C1-Like 1 (NPC1L1), and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) and Genetically Proxied LDL Cholesterol Levels and Overall and Histotype-Specific Invasive Epithelial Ovarian Cancer Among Women in the General Population.
| Outcome | Cases, No. | Odds Ratio (95% CI)a | P Value |
|---|---|---|---|
| HMG-CoA Reductase | |||
| Invasive epithelial ovarian cancer | 22 406 | 0.60 (0.43-0.83) | .002 |
| High-grade serous carcinoma | 13 037 | 0.70 (0.47-1.04) | .08 |
| Low-grade serous carcinoma | 1012 | 1.49 (0.22-10.05) | .68 |
| Mucinous carcinoma | 1417 | 0.53 (0.12-2.42) | .41 |
| Endometrioid carcinoma | 2810 | 0.40 (0.19-0.83) | .01 |
| Clear cell carcinoma | 1366 | 0.61 (0.19-1.92) | .40 |
| NPC1L1 | |||
| Invasive epithelial ovarian cancer | 22 406 | 0.97 (0.53-1.75) | .91 |
| High-grade serous carcinoma | 13 037 | 0.93 (0.46-1.88) | .83 |
| Low-grade serous carcinoma | 1012 | 0.34 (0.04-2.93) | .33 |
| Mucinous carcinoma | 1417 | 1.39 (0.23-8.24) | .72 |
| Endometrioid carcinoma | 2810 | 1.62 (0.44-5.92) | .47 |
| Clear cell carcinoma | 1366 | 0.43 (0.07-2.55) | .35 |
| PCSK9 | |||
| Invasive epithelial ovarian cancer | 22 406 | 0.97 (0.81-1.16) | .74 |
| High-grade serous carcinoma | 13 037 | 0.87 (0.79-1.20) | .82 |
| Low-grade serous carcinoma | 1012 | 1.21 (0.65-2.25) | .55 |
| Mucinous carcinoma | 1417 | 0.99 (0.58-1.66) | .96 |
| Endometrioid carcinoma | 2810 | 0.87 (0.55-1.39) | .57 |
| Clear cell carcinoma | 1366 | 1.05 (0.61-1.83) | .86 |
| LDL Cholesterol | |||
| Invasive epithelial ovarian cancer | 22 406 | 0.98 (0.91-1.05) | .55 |
| High-grade serous carcinoma | 13 037 | 1.00 (0.92-1.09) | .99 |
| Low-grade serous carcinoma | 1012 | 1.05 (0.85-1.29) | .68 |
| Mucinous carcinoma | 1417 | 0.80 (0.65-0.98) | .03 |
| Endometrioid carcinoma | 2810 | 0.92 (0.78-1.10) | .36 |
| Clear cell carcinoma | 1366 | 1.01 (0.85-1.21) | .90 |
The exponential change in odds of invasive epithelial ovarian cancer per genetically proxied inhibition of drug target equivalent to a 1-mmol/L (38.7-mg/dL) decrease in low-density lipoprotein (LDL) cholesterol or the exponential change in odds of invasive epithelial ovarian cancer per genetically proxied 1-mmol/L decrease in LDL cholesterol. Invasive histotypes classified as “other” by Ovarian Cancer Association Consortium (n = 2764) were included in analyses for invasive epithelial ovarian cancer but were not assessed separately. In histotype-stratified analyses, there was no statistically significant evidence of heterogeneity across the 5 histotypes assessed (P value for heterogeneity = .84; I2 = 0.00%). The P value for heterogeneity was calculated from a Cochran Q statistic where Q is distributed as a χ2 statistic with K (number of histotypes) – 1 degrees of freedom.