OBESITY AND CANCER

PARUNGAO - SAGAD
OBESITY
HOW DOES OBESITY LEAD TO CANCER?
Stone, T., McPherson, M., Darlington, L. (2018). Obesity and Cancer: Existing and New Hypotheses for a Causal Connection. EBioMedicine 30; 14–28.
COLON CANCER
 Sixteen studies were included in the meta-analysis assessing the association between obesity and
colon cancer among men and 13 studies among women
 Obese men had an increased risk of colon cancer compared to men of normal weight
 Obese women had an increased risk of colon cancer compared to women of normal weight
 Case control conducted in the USA: Men w/ colorectal CA had increased leptin but there were other
studies that disproved this correlation
 Leptin activates P13K-AKT pathway / Jak2-STAT3 pathway -> increases cancer cell proliferation which would
suggest a strong stimulation of colon cancer
 This study was done on human colorectal cancer cell line
ENDOMETRIAL CANCER

 The pooled risk ratio from 16 studies illustrated that obese women had
an increased risk of endometrial cancer compared to women of normal
weight
 There were no enough data pooled for men
ESOPHAGEAL CARCINOMA

 3 studies showing obese men didn’t have an increased risk compared to

men with normal weight
 4 studies reporting obese women had increased risk compared to
women with normal weight
 Both having significant heterogeneity
GALLBLADDER CANCER

 According to 4 studies assessing a link between cancer and

obesity, both obese men & women had increased risk compared
to normal weight w/o significant heterogeneity
LEUKEMIA

 Two studies assessed the association between obesity and leukemia

among men and women
 No increased risk in obese men
 Risk in obese women > risk in women of normal weight
 No significant heterogeneity across studies for both men and women
MALIGNANT MELANOMA
 Four studies in men and three in women assessed the association
between obesity and malignant melanoma
 Risk in obese men > risk in men of normal weight
 No significant heterogeneity

 No increased risk in obese women

 No significant heterogeneity
MULTIPLE MYELOMA

 Obese men had significantly lower risk of multiple myeloma compared to

men of normal weight
 Increased risk of multiple myeloma compared to women of normal
weight
 There was no significant heterogeneity across the two studies
NON-HODGKIN LYMPHOMA
 Four studies in men and six in women assessed the association between obesity and
non-Hodgkin lymphoma
 No increased risk of non-Hodgkin lymphoma among obese men compared to men of
normal weight
 There was no significant heterogeneity across studies

 Among obese women, however, the pooled risk ratio showed a reduced risk of non-
Hodgkin lymphoma compared to women of normal weight
 There was significant heterogeneity across studies
PANCREATIC CANCER
 Nine studies in men and ten studies in women assessed the association
between obesity and pancreatic cancer
 Risk in obese men > risk in men of normal weight
 There was significant heterogeneity across studies

 Risk in obese women > risk in women of normal weight

 However , there is no heterogeneity across studies
A schematic representation of obesity- and diabetes-associated pancreatic cancer. High fat/caloric intake results in accumulation of
excess fat, which further leads to development of obesity. A. In obesity, adipose tissue releases free fatty acids (ffas), which enter
circulation and accumulate in the non-adipose tissues such as muscle, liver and pancreas that leads to insulin resistance and
diabetes. B. Along with ffas, adipokines, altered gut microbiota and inflammatory markers contribute to pancreatic cancer
development through unknown mechanisms.
BREAST CANCER
 Patients w/ breast CA had increased levels of leptin receptors in the tumors & serum
leptin levels, leading to poorer prognosis as compared to those without these factors
 Leptin activated JAK-STAT & P13K signaling pathway and induces self-renewal
capacity of cancer stem cells (CSCs), leading to recurrence and metastasis
 Adiponectin has proangiogenic effects that enhances tumor neovascularization
 Consistent with accumulation of sphingosine-1-phosphate which is a proangiogenic stimulus when
there is increased levels of adiponectin
RECTAL CANCER
 There were 11 studies for men and 9 for women that assessed the association
between obesity and rectal cancer
 The pooled risk ratio illustrated that obese men had no increased risk of rectal
cancer compared to men of normal weight (RR 1.22; 95% confidence interval 0.91 to
1.64, P = 0.00001)
 Similarly among obese women the pooled risk ratio illustrated no increased risk
of rectal cancer compared to women of normal weight (RR 1.03; 95% confidence
interval 0.74 to 1.44, P = 0.00001)
RENAL CANCER
 A meta-analysis of 21 cohort studies showed that there is a significant association of
renal cell cancer (RCC) among the overweight (pre-obesity and obesity)
 Dose response analysis in the same study showed each 1kg/m² increment of BMI
corresponded with a 4% increased risk of (RCC) however this estimate broke down
in higher BMI categories
 The study claimed that the increase cancer risk might be through hormonal
mechanisms such as insulin growth factor
THYROID CANCER
 There were 6 studies among men and 4 studies among women assessing the
association between obesity and thyroid cancer and 4 studies among women
 The pooled risk ratio illustrated that obese men had no increased risk of thyroid
cancer compared to men of normal weight (RR 1.12; 95% confidence interval 0.72 to
1.72, P < 0.00001)
 Likewise, among obese women the pooled risk ratio demonstrated no increased
risk of thyroid cancer compared to women of normal weight (RR 1.03; 95%
confidence interval 0.87 to 1.23, P < 0.004)
SUMMARY
MEN WOMEN
 Colon  Colon  Pancreatic
 Gallbladder  Endometrial  Postmenopausal
 Malignant Melanoma  Esophageal breast CA

 Pancreatic  Gallbladder  Renal

 Renal  Leukemia
REFERENCES
 Dobbins, M., Decorby, K. and Choi, BCK (2013). Association between obesity and cancer risk: Meta-analysis of
observational studies. ISRN Preventive Medicine. Retrieved from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062857/pdf/ISRN.PM2013-680536.pdf.
 Park, J. et al (2014). Obesity and Cancer - Mechanisms underlying tumour progression and recurrence. Nat Rev
Endocrinol. 10 (8): 455-465. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374431/pdf/nihms-
631734.pdf.
 Stone, T., McPherson, M., Darlington, L. (2018). Obesity and Cancer: Existing and New Hypotheses for a Causal
Connection. EBioMedicine 30; 14–28. Retrieved from: http://www.sciencedirect.com/science/journal/23523964
 Wang, F., & Xu, Y. (2014). Body mass index and risk of renal cell cancer: A dose‐response meta‐analysis of
published cohort studies. International journal of cancer, 135(7), 1673-1686. Retrieved from:
https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.28813