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Differences In Diet
An important difference between the lifestyle of hunter-gatherers and modern populations is diet. Paleolithic humans consumed game that had lower fat and cholesterol content than domestic meat, in addition to consuming seafood and fish high in omega-3 fatty acids. The Paleolithic diet was also high in protein, fiber, and healthy fats, making it ideal for maintaining optimal health, while the western diet is mostly comprised of dairy, oils, and sugar that make it difficult for the body to receive the nutrients it needs. During the neolithic and agricultural eras, cereals, alcoholic beverages, nonhuman milk were introduced, foods that the human body is not adapted to. Plant based foods also provided certain benefits to Paleolithic humans. Nuts were eaten as they contain high energy and healthy fats and were most likely a staple in the Paleolithic diet. Seeds were also available to certain Paleolithic humans depending on geographic region, and included maize, wheat, rice, and seeds from legumes. These seeds provided less energy than the corn, wheat, rice, and legumes we know today and were often consumed less often. The dangers of consuming too much of one seed include the prevalence of plant lectins, which are resistant to enzymatic breakdown in the intestines, and can harm the membranes of organs. Paleolithic humans were able to combat this by consuming a variety of seeds, not consuming the same one everyday, and avoiding seeds known to be harmful. Another difference in diet is the consumption of dairy products. Dairy is a large part of the modern western diet and  is linked to many health issues such as diabetes, cardiovascular mortality, and coronary heart disease. The benefits of dairy including calcium absorption to reduce risk of bone fractures can be overstated, with supplements only providing a marginal benefit.

Evolutionary Theories and Genetics
A significant concept in explaining diseases of affluence is that the human genome is congruent with the Paleolithic lifestyle, also known as the mismatch hypothesis. One example is developed leptin resistance, a critical factor in many diseases of affluence including cardiovascular disease, obesity, and diabetes. Based on molecular and archeological evidence, one hypothesis suggests that leptin resistance formed in modern humans since humans are not evolutionarily adapted to a cereal-based diet. Evidence includes “higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed” when pigs were fed a cereal-free hunter gatherer diet and some were feed a western diet. Another concept, the thrifty genotype theory, suggests that the human genotype developed to store fat in cases of famine, however now contributes to the storage of fat. This potentially explains why certain groups, such as the Pima Indians, who relied on large unpredictable game resources now have high rates of obesity and diabetes. Another theory, entitled the young hunter theory, asserts that hunters needed to have a certain muscular status; as they aged,  the metabolic processes redirected towards energy conservation. In addition, there are other potential genetic factors that could contribute to diseases of affluence, such as perinatal diet and assortative mating. The foods consumed while a woman is pregnant can cause epigenetic changes that modify the metabolism and energy balance for the child. Assortative mating is the idea that those who are overweight or obese tend to mate with each other, exposing the children to alleles that increase the risk of being overweight.

Evolutionary Perspectives (Mental Illness)
There are multiple evolutionary hypothesis that could explain the increased prevalence of mental illness in affluent countries. One is the polygenic mutation- selection balance, which suggests that multiple genetic factors contribute to mental illness and are “under negative selection pressure”. Since there are many genes that impact mental illness, there is a large mutational target size. Another explanation is the mismatch hypothesis, stating that a change in the environment caused adaptive or fitness-neutral genes to become fitness-reducing. The APOE*4 allele, for example, is associated with CVD and Alzheimer’s, however could have been adaptive in Paleolithic times.

Cancer
In United States, 1,735,350 new cases of cancer will be diagnosed in 2018. Most common forms of cancer are cancer of the breast, lung, bronchus, prostrate, colorectal cancer, melanoma of skin, Non-Hodgkin's lymphoma, renal cancer, thyroid cancer and liver cancer. According to the American Cancer Society, lung cancer was the leading cause of death for males in 2008, as well as the most diagnosed cancer in 2008. The highest rates of lung cancer were found to be in Eastern and Southern Europe and North America Cancer mortality is also higher among men than in women while African-Americans have the highest risk of mortality due to cancer.[56] Cancer is also the leading cause of death in Australia. The most common cancers in Australia are prostrate, breast, colorectal, melanoma and lung cancer. These account for 60% of the cancer cases diagnosed in Australia.[57]

Europe contains only 1/8 of the world population, but has around one quarter of the global cancer cases, with 3.7 million new cases each year. Lung, breast, stomach, liver, colon are the most common cancers in Europe.[58] The overall incidences among different cancers vary across countries.[59]

About one in two Canadians will develop cancer in their lifetime, and one in four will die of the disease. In 2017, 206,200 new cases of cancer were diagnosed. Lung, colorectal, breast, and prostate cancer accounted for about half of all cancer diagnoses and deaths.[60]

Risk Factors
High prevalence of cancer in high-income countries is attributed to lifestyle factors like obesity, smoking, physical inactivity, diet and alcohol intake.[61] Education level, income, diets high in meat and fat, as well as alcohol consumption contribute to the high prevalence of cancer. Around 40% of the cancers can be prevented by modifying these factors. [62]

Hygiene Hypothesis
The hygiene hypothesis is a concept that deems to explain an increase in severe allergies within the western world. It proclaims that due to a lack of exposure to certain entities in early childhood, the immune system fails to recognize allergens in the same way than if it had been more exposed. . As it is increasingly common for parents to prevent exposure to allergens in their children’s early years, children commonly have allergies to those very foods. A combination of a sterile environment and a lack of diverse foods can create allergens in children whose immune systems lack the maturity to properly defend the body.