The mechanisms by which<unk>  may increase the risk of cancer are not well understood, but it is believed that the combined effects of the adipose tissue environment and the endocrine alterations that accompany it among obese people both interact to promote tumor initiation and progression. Adipose tissue also creates an inflammatory environment that enhances the ability of tumor cells to metastatize. The U.S National Cancer Institute indicates that one of the main ways in which<unk>  can cause cancer is by promoting chronic low-level inflammation, which can, over time, cause DNA damage that leads to cancer. Articles supporting this view were reviewed by Cerda et al. There are also a number of hormonal, metabolic and other changes caused by<unk>  that may affect carcinogenesis. A review by Tahergorabi et al. summarizes articles indicating that<unk>  induces changes in angiogenesis, inflammation, interaction of proinflammatory cytokines, endocrine hormones, adipokines including leptin and adiponectin, insulin, growth factors, estrogen, progesterone and cell metabolism. DNA damage appears to be the primary cause of cancer (see Carcinogenesis). It is not clear which factor(s) altered by<unk>  are major source(s) of the DNA damages causing increased cancer risk in obese individuals. However, both reduced DNA repair and increased DNA damage are observed in obese individuals. Reduced DNA repair As first noted in 2005, there is evidence that overweight/obesity is associated with reduced DNA repair capacity. This was shown, in particular, in women with breast cancer. Lymphocytes from postmenopausal obese women also have reduced DNA repair capacity compared to non-obese postmenopausal women. If DNA repair is reduced by<unk> , this would allow DNA damages to accumulate. Excess DNA damages, when present in replicating cells, can cause an increase in oncogenic mutations through error-prone translesion synthesis during replication. Increased DNA damage An 8-fold and 5.6-fold increase in nuclear damage was observed in lymphocytes of obese and overweight children respectively, compared to children of normal weight, evaluated by the gamma-H2AX focus assay. The gamma-H2AX assay generally reflects the presence of double-strand breaks in DNA, though the assay may indicate other DNA damages as well. Similarly, there was a 2.7-fold and 2.5-fold increase in micronuclei in lymphocytes of obese and overweight children respectively, compared to children of normal weight. Micronuclei are usually a sign of genotoxic events and chromosomal instability (see Micronucleus). 8-dihydro-2'-deoxyguanosine (8-oxodG) concentration in peripheral blood lymphocytes is an index of nuclear DNA damage. 8-oxodG damages are mutagenic. The level of 8-oxodG was measured in 58 overweight and obese adult patients as well as in 20 normal weight individuals. The level of 8-oxodG correlated positively with body mass, BMI, hip circumference and triglyceride concentration. In a study by Donmez-Altuntas et al., 83 obese, 21 over-weight and 21 normal-weight subjects were tested. Frequencies of DNA damages as measured by frequencies of micronuclei, nucleoplasmic bridges and nuclear buds were found to be significantly higher in lymphocytes of obese subjects than in normal-weight and over-weight subjects (p<0.01 and p<0.05) respectively. Hofer et al., used the enzyme formamidopyrimidine DNA glycosylase (FPG) and gel electrophoresis to measure levels of DNA damage (oxidized purines). They found two factors that can affect DNA damage in a young healthy population. These were fruit intake (high intake; lower DNA damage) and BMI (high BMI; higher DNA damage). In the study by Tafurt-Cardona et al., described above, where they found reduced DNA repair in obese postmenopausal women, they also found increased DNA damages, as measured by frequencies of chromosome aberrations, in the obese postmenopausal women.
Obesity and cancer
Alcohol and cardiovascular disease
Alcohol and cancer
Alcohol and breast cancer
Alcohol and pregnancy
Diabetes and pregnancy
Women and smoking
Pregnancy vegetarianism