Obesity potentially linked to 18 additional cancers, expands understanding of risks

In a groundbreaking study recently published in The Lancet Regional Health – Europe, researchers have further explored the complex associations between body mass index (BMI) and the risk of developing obesity-related cancers. The study builds on previous findings and uncovers 18 additional cancers that may be linked to obesity, broadening the scope of understanding in the field of cancer research.

The rising prevalence of obesity and overweight worldwide underscores the urgency of understanding their impact on morbidity. Increasing evidence suggests that obesity is not just a health risk but may also serve as a preventable cause of various cancers. The 2016 report by the International Agency for Research on Cancer (IARC) had already established a connection between BMI and 13 specific cancers, laying the groundwork for further exploration.

Building on these earlier findings, an umbrella review later confirmed that most of these cancers were indeed linked to obesity. However, much of the existing research has focused on overall cancer risk without delving deeply into the associations between BMI and specific morphological cancer subtypes.

The present study seeks to bridge this gap by investigating potential obesity-related cancers, including their subtypes, and by quantifying the strength of these associations. The researchers utilised data from the Obesity and Disease Development Sweden (ODDS) study, drawing from an extensive database that spans several decades.

Cancer diagnoses recorded between 1963 and 2019 were meticulously identified through the Swedish Cancer Register, which classified cancers using standardised codes. The 13 cancers previously recognised by the IARC as obesity-related served as a foundation for this study, but the researchers also applied an explorative decision algorithm to identify additional cancers potentially linked to obesity. These were defined as cancers showing a positive association with increased obesity risk, either compared to normal weight or per a 5 kg/m² increase in BMI.

To determine the strength of the association between BMI and cancer risk, BMI was evaluated in categorical terms (such as underweight, overweight, etc.) or per a 5 kg/m² increment, provided there were sufficient cases—250 for categorical evaluations and 100 for incremental evaluations.

The analysis employed Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). These models were stratified by birth year and sex, and adjustments were made for several variables, including baseline age, mode of height and weight assessment, education level, country of birth, and marital status. Additionally, for cancers known to be related to smoking, the models were repeated in individuals with available smoking data to adjust for this significant confounder. The Wald test was then utilised to examine potential interactions based on sex.

The study’s scope was vast, including 4.14 million individuals—2.01 million females and 2.12 million males—with an average baseline age of 31.3 years for females and 23.1 years for males. The average BMI recorded was 22.5 kg/m² for males and 24 kg/m² for females, with obesity prevalence noted at 9% in females and 3% in males. Over a median follow-up period of 24.2 years, 332,501 cancer cases were identified—139,685 in females and 192,816 in males. The median age at cancer diagnosis was 55.7 years for females and 63.1 years for males.

The findings revealed that obesity was associated with an elevated risk of 18 cancers (16 in females and 15 in males) relative to normal weight or per a 5 kg/m² increase in BMI. Importantly, these cancers had not previously been established as obesity-related and accounted for 15% of all cancer cases identified in the study.

For females, these potential obesity-related cancers included those of the cervix, vulva, head and neck (specifically squamous cell carcinoma), and nodular melanoma. For males, the study identified cancers of the penis, head and neck (particularly adenocarcinoma), and malignant melanoma. Moreover, both sexes exhibited increased risks for cancers of the small intestine, stomach, oral cavity, paranasal and nasal sinuses, biliary tract, adrenal glands, pituitary gland, pancreatic islets, connective tissue, parathyroid gland, and both myeloid and lymphoid neoplasms.

Interestingly, there were notable sex-based interactions in the risk of certain cancers, including malignant melanoma, lymphoid neoplasms, and cancers of the lip, head and neck, tongue, and connective tissue. Additionally, specific subtypes of some potential obesity-related cancers demonstrated a stronger association with BMI than others. When smoking was considered, the association between BMI and some cancers persisted, while it weakened for others.

Beyond these newly identified cancers, obesity was also linked to an increased risk of all established obesity-related cancers, which constituted a quarter of all cases. The hazard ratios for these established and potential obesity-related cancers were 1.17 and 1.24 in males and 1.13 and 1.12 in females, respectively.

The absolute risk of developing a potential obesity-related cancer by the age of 80 was 5.7% for males with obesity and 5.5% for those with normal weight. In females, the corresponding risks were 4.2% for those with obesity and 3.5% for those with normal weight. When considering both established and potential obesity-related cancers, the combined risk by age 80 was 14.2% for males with obesity compared to 12% for those with normal weight, and 18.7% for females with obesity compared to 16.3% for those with normal weight.

In summary, this study has significantly expanded the list of cancers potentially linked to obesity, identifying 18 new cancers across various organ systems, including the gastrointestinal tract, endocrine organs, head and neck, genitals, and haematological malignancies. While the association between BMI and these newly identified cancers was somewhat weaker in males compared to the established obesity-related cancers, it was comparable in females. The findings underscore the need for further studies that account for cancer-specific confounders to validate these associations and deepen our understanding of the complex relationship between obesity and cancer.