Body Mass Index and Risk of Female Reproductive System Tumors Subtypes: A Meta-Analysis Using Mendelian Randomization

Area of Science:

• Genetics
• Oncology
• Reproductive Health

Background:

• A known association exists between body mass index (BMI) and female reproductive system tumors, but the causal relationship remains unclear.
• Previous studies suggest a link, necessitating further investigation into the genetic underpinnings of this association.

Purpose of the Study:

• To investigate the potential causal relationship between genetically predicted BMI and the risk of developing common female reproductive system tumors using a Mendelian randomization (MR) approach.
• To identify specific tumor types within the female reproductive system that are causally associated with higher BMI.

Main Methods:

• A two-sample Mendelian randomization (MR) study was employed.
• Genetic instrumental variables for BMI were derived from a large genome-wide association study (GWAS) meta-analysis.
• Summary statistics for five common female reproductive system tumors were obtained from large-scale consortia, including FinnGen and UK Biobank.

Main Results:

• Genetic predisposition to higher BMI was significantly associated with an increased risk of multiple female reproductive system tumors.
• Specific associations were observed for breast cancer (overall and ER-positive/negative subtypes), endometrial carcinoma, and various subtypes of ovarian cancer (high-grade serous, low-grade malignant serous, and endometrioid).
• No significant causal association was found between genetically predicted BMI and uterine fibroids, cervical precancerous lesions, or cervical cancer.

Conclusions:

• A genetic link exists between a higher BMI and an elevated risk of developing several female reproductive system tumors.
• These findings emphasize the importance of weight management strategies for the prevention of reproductive system cancers in women with high BMI.
• The study provides genetic evidence supporting the role of BMI in the etiology of specific gynecological malignancies.